A Phase 3, Multicenter, Open-Label Study to Evaluate the Long-term Safety, Tolerability, and Efficacy of TAK-279 in Subjects with Moderate-to-Severe Plaque Psoriasis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Takeda Development Center Americas Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

1 Apr 2025 → ongoing

Decision date (initial)

2025-01-21

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Takeda Development Center Americas, Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacogenetic, Efficacy

To evaluate the long-term safety and tolerability of TAK-279 orally administered once daily (QD) in subjects with moderate-to-severe plaque psoriasis.

Secondary objectives 1

1. To evaluate the long-term efficacy of TAK-279 orally administered QD in subjects with moderate-to-severe plaque psoriasis.

Conditions and MedDRA coding

Moderate to Severe Plaque Psoriasis

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Part A: Subject Willingness 1.Subject is willing and able to understand and fully comply with study procedures and requirements (including digital tools and applications, as necessary), in the opinion of the investigator.
2. Part A: Subject Willingness 2.Subject has provided written informed consent and any required privacy authorization before the initiation of any study procedures.
3. Part A: Age and Reproductive Status: 3.Subject is aged 18 years or older at the time of consent. In the European Union (EU)/ European Economic Area (EEA) and the United Kingdom (UK), for subjects aged 65 years or older, the investigator must document a favorable benefit-risk assessment to justify the subject’s inclusion in the study.
4. Part A: Age and Reproductive Status: 4.Subject meets the following birth control requirement: An individual with potential for pregnancy who is now of nonchildbearing potential with laboratory confirmation of postmenopausal status (see Section 10.4.1 for definitions); or, if sexually active with a nonsterilized individual who produces sperm, an individual with potential for pregnancy who agrees to use a highly effective method of contraception from the signing of informed consent throughout the duration of the study and for 10 days after the last dose. The use of effective contraception is not required for assigned male sex at birth subjects during the duration of the study. In the EU/EEA and the UK, for subjects who elect to use hormonal contraception as a form of highly effective contraception, the investigator must document a favorable benefit-risk assessment to justify the subject’s inclusion in the study at screening and every 3 months during the study. Note: Oral hormonal contraception may be susceptible to interaction with TAK-279 which may reduce the efficacy of the contraceptive method. Therefore, if a subject is on a form of oral contraception, a second highly effective or effective method of contraception should be used during the treatment period and for at least 10 days after the last dose of study treatment if the subject is sexually active with a partner with whom the subject could become pregnant. A barrier method is recommended, preferably a male condom.
5. Part A: Age and Reproductive Status: 5.For subjects in the EU/EEA or UK, the investigator must have no reason to believe that the participant would be placed at risk by participating in the trial with regard to the European Commission decision as of 10 March 2023 on measures to minimize risk of serious side effects with JAK inhibitors (EMA/142279/2023) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) guideline on JAK inhibitors: new measures to reduce risks of major cardiovascular events, malignancy, venous thromboembolism, serious infections and increased mortality as of 26 April 2023 (Drug Safety Update volume 16, issue 9).
6. Part A: Disease Characteristics: 6.Subject has a diagnosis of chronic plaque psoriasis for ≥6 months prior to the screening visit.
7. Part A: Disease Characteristics: 7.Subject has stable plaque psoriasis defined as no significant flare or change in morphology (as assessed by the investigator) in psoriasis for ≥6 months before screening.
8. Part A: Disease Characteristics: 8.Subject has moderate-to-severe plaque psoriasis as defined by a PASI score ≥12 and an sPGA score ≥3 at screening and Day 1.
9. Part A: Disease Characteristics: 9.Subject has plaque psoriasis covering ≥10% of his or her total BSA at screening and Day 1.
10. Part A: Disease Characteristics: 10.Subject must be a candidate for phototherapy or systemic therapy.
11. Part A: Other: 11.In the EU/EEA and the UK, for subjects currently smoking or using chewing tobacco or with a history of long-term smoking (≥20 pack years) or chewing tobacco use, the investigator must document a favorable benefit-risk assessment to justify the subject's inclusion in the study.
12. Part B: Subject Willingness: 1. Subject is willing and able to understand and fully comply with study procedures and requirements (including digital tools and applications, as necessary), in the opinion of the investigator.
13. Part B: Subject Willingness: 2.Subject has provided written informed consent and any required privacy authorization before the initiation of any study procedures.
14. Part B: Age and Reproductive Status: 3.Subject meets the following birth control requirement: •An individual with potential for pregnancy who is now of nonchildbearing potential with confirmation of postmenopausal status (see Section 10.4.1 for definitions); or, if sexually active with a nonsterilized individual who produces sperm, an individual with potential for pregnancy who agrees to use a highly effective method of contraception from the signing of informed consent throughout the duration of the study and for 10 days after the last dose. The use of effective contraception is not required for assigned male sex at birth subjects during the duration of the study. In the EU/EEA and the UK, for subjects who elect to use hormonal contraception as a form of highly effective contraception, the investigator must document an updated favorable benefit-risk assessment to justify the subject’s inclusion in the study at screening and every 3 months during the study, taking into account any changes since initial assessment at entrance to the parent trials or Part A. Note: Oral hormonal contraception may be susceptible to interaction with TAK-279 which may reduce the efficacy of the contraceptive method. Therefore, if a subject is on a form of oral contraception, a second highly effective or effective method of contraception should be used during the treatment period and for at least 10 days after the last dose of study treatment if the subject is sexually active with a partner with whom the subject could become pregnant. A barrier method is recommended, preferably a male condom.
15. Part B: Age and Reproductive Status: 4.Subject has completed 52 weeks of treatment (TAK-279-3001 or Part A) or 60 weeks of treatment (TAK-279-3002), or 16 weeks of treatment (TAK-279-PsO-3004) in their parent study or Part A.
16. Part B: Age and Reproductive Status: 5.Participation would not put the subject at undue risk or interfere with interpretation of study results, in the opinion of the investigator.
17. Part B: Age and Reproductive Status: 6.For subjects in the EU/EEA or UK, the investigator must have no reason to believe that the participant would be placed at risk by participating in the trial with regard to the European Commission decision as of 10 March 2023 on measures to minimize risk of serious side effects with JAK inhibitors (EMA/142279/2023) and the UK Medicines and Healthcare products Regulatory Agency (MHRA) guideline on JAK inhibitors: new measures to reduce risks of major cardiovascular events, malignancy, venous thromboembolism, serious infections and increased mortality as of 26 April 2023 (Drug Safety Update volume 16, issue 9), taking into account any changes in medical or other history since initial assessment at entrance to the parent trials or Part A.
18. Part B: Other: 7.In the EU/EEA and the UK, for subjects currently smoking or using chewing tobacco or with a history of long term smoking (≥20 pack years) or chewing tobacco use, the investigator must document an updated favorable benefit-risk assessment to justify the subject’s inclusion in the study, taking into account any changes since initial assessment at entrance to the parent trials or Part A.

Exclusion criteria 63

1. Part A: Target Disease-Related Exclusions: 1.Subject has evidence of non-plaque psoriasis (erythrodermic, pustular, predominantly guttate psoriasis, predominantly inverse, or drug-induced psoriasis). If a subject meets criteria for inclusion based on typical plaque psoriasis presentation, a limited amount of inverse psoriasis is not exclusionary.
2. Part A: Target Disease-Related Exclusions: 2.Subject requires systemic treatment, other than nonsteroidal anti-inflammatory drugs, during the trial period for an immune-related disease (eg, inflammatory bowel disease).
3. Part A: Target Disease- Related Exclusions: 3.Subject has a history of excessive sun exposure, has used tanning booths within 4 weeks prior to Day 1, or is not willing to minimize natural and artificial sunlight exposure during the study period. Use of sunscreen products and protective apparel is recommended when sun exposure cannot be avoided.
4. Part A: Target Disease-Related Exclusions: 4.Subject has concomitant comorbid skin condition that, in the opinion of the investigator, would interfere with the study assessments.
5. Part A: Recent/Concurrent Infectious Disease Exclusions: 5. Tuberculosis (TB): a)Subject has history of active TB infection, regardless of treatment status. b)Subject has signs or symptoms of active TB (including, but not limited to, chronic fever, chronic productive cough, night sweats, or weight loss) as judged by the investigator. c)Subject has evidence of latent TB infection (LTBI) as evidenced by a positive QuantiFERON-TB Gold (QFT) result OR 2 indeterminate QFT results and subject does not have documentation of appropriate LTBI prophylaxis or is not able or not willing to initiate appropriate LTBI prophylaxis. Subject remains eligible if there are no signs/symptoms of active TB AND documentation of no history of active TB can be provided AND (1) subject can provide documentation of prior and complete treatment for LTBI (appropriate in duration and type per current local country guidelines) or (2) subject has a positive QFT result or 2 indeterminate QFT results but has initiated prophylaxis (appropriate in duration and type per current local guidelines) a minimum of 2 weeks prior to Day 1. In the EU/EEA and the UK, subjects with evidence of LTBI, regardless of prophylaxis treatment status, must receive approval to participate in the study from an infectious disease or other TB specialist (eg, pulmonologist). Note: TB prophylaxis regimens should be administered according to local guidelines; however, because of potential interactions with TAK-279, rifampin should not be used. TB testing should be conducted using QuantiFERON-TB Gold submitted to central laboratory unless alternate or additional tests are required per local guidelines. d)Subject has had any imaging study during or 6 months prior to screening, including x-ray, chest computed tomography, magnetic resonance imaging, or other chest imaging suggesting evidence of current active or a history of active TB. X-ray is required for all subjects regardless of QuantiFERON-TB Gold results unless the subject has had normal chest imaging in the 6 months prior to screening.
6. Part A: Recent/Concurrent Infectious Disease Exclusions: 6.Herpes infections: a)Subject has active herpes virus infection, including herpes zoster or herpes simplex 1 and 2 (demonstrated on physical examination and/or medical history) at screening or Day 1. b)Subject has history of serious herpetic infection that includes any episode of disseminated disease, multidermatomal herpes zoster, herpes encephalitis, ophthalmic herpes, or recurrent herpes zoster (defined as 2 episodes within 2 years).
7. Part A: Recent/Concurrent Infectious Disease Exclusions: 7.Non-herpetic viral diseases: a)Subject has presence of hepatitis C virus (HCV) antibody and a positive confirmatory test result for HCV RNA (nucleic acid test or polymerase chain reaction). In the EU/EEA and the UK, if the subject has total anti-HCV Ab positivity at screening but is confirmed to have no detectable HCV RNA by PCR testing, HCV RNA PCR testing will be assessed every 3 months until end of trial. b)Subject has presence of positive hepatitis B surface antigen (HBsAg+), or indeterminate hepatitis B surface antigen, presence of hepatitis B virus DNA (regardless of serology), or positive anti-hepatitis B core antibody without concurrent positive hepatitis B surface antibody (HBcAb+ and HBsAb-). In the EU/EEA and the UK, if the subject has total anti-HBc Ab positivity at screening but is confirmed to have no detectable HBV DNA by PCR testing, the subject will repeat HBV DNA PCR testing every 3 months until the end of trial; if a subject has anti-HBs Ab positivity at screening but is confirmed to have no detectable HBV DNA by PCR testing, unless the subject has documented completion of the HBV vaccination series by medical records, the subject will repeat HBV DNA PCR testing every 3 months until the end of trial. c)Subject has positive results for HIV by serology, regardless of viral load.
8. Part A: Recent/Concurrent Infectious Disease Exclusions: 8.Other infectious diseases: a)Subject has a history of active infection or febrile illness within 7 days prior to Day 1, as assessed by the investigator. b)Subject has history of symptoms suggestive of systemic or invasive infection within 30 days prior to Day 1. c)Subject has history of bacterial, viral, or fungal infection that required hospitalization or treatment with intravenous antimicrobial therapy within 8 weeks prior to Day 1, or oral antimicrobial therapy within 30 days prior to Day 1. d)Subject has a history of chronic or recurrent bacterial disease, including but not limited to chronic pyelonephritis or cystitis, chronic bronchitis/pneumonitis, osteomyelitis, or chronic skin ulcerations/infections or fungal infections (except superficial onychomycosis). e)Subject has a history of an infected joint prosthesis unless that prosthesis has been removed or replaced at least 60 days prior to Day 1. f)Subject has a history of opportunistic infections (eg, Pneumocystis jirovecii pneumonia, histoplasmosis, coccidiomycosis). g)Subject had a bacterial infection within 60 days prior to Day 1 for which he or she did not receive treatment.
9. Part A: Noninfectious Disorders Exclusions: 9.Subject has any clinically significant medical condition, evidence of an unstable clinical condition (eg, cardiovascular, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, or immunologic), or vital signs/physical/laboratory/electrocardiogram (ECG) abnormality that would, in the opinion of the investigator, put the subject at undue risk or interfere with interpretation of study results. These include but are not limited to: a)Subject has a history of known or suspected condition/illness that is consistent with compromised immunity, including but not limited to any identified congenital or acquired immunodeficiency; splenectomy. b)Subject had a major surgery within 60 days prior to Day 1 or has a major surgery planned during the study. c)Subject has unstable, poorly controlled, or severe hypertension at screening, confirmed by 2 repeat assessments. d)Subject has a history of Class III or IV congestive heart failure as defined by New York Heart Association criteria. e)Subject has a history of cancer or lymphoproliferative disease with the exception of successfully treated nonmetastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix; in the EU/EEA and the UK, investigators must document a favorable benefit-risk assessment. f)For subjects with asthma, chronic obstructive pulmonary disease, or other pulmonary illnesses, subject has been hospitalized in the past 3 months, has ever required intubation for treatment, currently requires oral corticosteroids, or has required more than 1 course of oral corticosteroids within 6 months prior to Day 1. g)Subject has any of the following cardiovascular disease history: •A new diagnosis of atrial fibrillation or an episode of atrial fibrillation with rapid ventricular response or other dysrhythmia, non-acute cardiac hospitalization (eg, pacemaker implantation), pulmonary embolism, or deep venous thrombosis within the past 6 months prior to screening. •Any history of cerebrovascular event, myocardial infarction, coronary stenting, or aortocoronary bypass surgery. If, however, the investigator determines there are no suitable treatment alternatives available for the subject and it has been at least 6 months since the occurrence of any such event, the subject may enroll; in the EU/EEA and the UK, investigators must document a favorable benefit-risk assessment. h)Subject has ECG abnormalities that are considered clinically significant and would pose an unacceptable risk to the subject if they participated in the study, in the opinion of the investigator. i)Subject has significant/uncontrolled psychiatric illness, in the opinion of the investigator. j)Subject has any lifetime history of suicidal ideation, suicidal behavior, or suicidal attempts by 1) medical history; or 2) by C SSRS documentation or by answering “yes” to Question 5 for suicidal ideation on the C-SSRS at screening; or 3) is clinically deemed to have a suicide risk by the investigator. k)Subject has an 8-item PHQ-8 score of 15 or above at screening. l)Subject has a history of clinically significant drug or alcohol abuse within 12 months prior to Day 1.
10. Prohibited Psoriasis Treatments Exclusions: For the below prohibited psoriasis treatments, the washout period prior to Day 1 is within the time frame indicated or 5 half-lives, whichever is longer.Note: If the participant is currently receiving an approved therapy for psoriasis that is not permitted in the trial, but the approved therapy is well-tolerated and effective for moderate-to-severe psoriasis in the opinion of the participant and the investigator, the participant should not discontinue this therapy solely to enter the clinical trial. 10.Subject has received any of the following biologics or biosimilar versions within the time frame indicated: a)Antibodies to IL-12/-23, IL-17, or IL-23 (eg, ustekinumab, secukinumab, tildrakizumab, ixekizumab, or guselkumab) within 6 months prior to Day 1. b)TNF inhibitor(s) (eg, etanercept, adalimumab, infliximab, certolizumab) within 2 months prior to Day 1. c)Agents that modulate integrin pathways to impact lymphocyte trafficking (eg, natalizumab) or agents that modulate B cells or T cells (eg, alemtuzumab, abatacept, or visilizumab) within 3 months prior to Day 1. d)Rituximab or other immune cell-depleting therapy within 6 months prior to Day 1.
11. Part A: Prohibited Psoriasis Treatments Exclusions: For the below prohibited psoriasis treatments, the washout period prior to Day 1 is within the time frame indicated or 5 half-lives, whichever is longer. 11.Subject has used medicated shampoo and/or body wash, including formulations containing but not limited to salicylic acid, corticosteroids, coal tar, vitamin D3 analogues, or other compounds used for the management of psoriasis within 2 weeks prior to Day 1.
12. Part A: Prohibited Psoriasis Treatments Exclusions: For the below prohibited psoriasis treatments, the washout period prior to Day 1 is within the time frame indicated or 5 half-lives, whichever is longer.12.Subject has used any topical medication that could affect psoriasis presentation (including but not limited to corticosteroids, salicylic acid, urea, alpha- or beta-hydroxy acids, anthralin, retinoids, vitamin D analogues [such as calcipotriol], methoxsalen, trimethylpsoralen, calcineurin inhibitors [eg, tacrolimus], tapinarof, roflumilast, JAK inhibitors, or tar) within 2 weeks prior to Day 1. Note: Low-potency topical steroids (World Health Organization Class VI and VII) are permitted on the palms, soles, face, intertriginous areas, and/or genitals but should not be used within 24 hours before any study visit. Low-potency topical steroids may be used to treat acute non psoriatic conditions (eg, contact dermatitis) on all body regions for no more than 2 weeks but should not be used within 24 hours before any study visit. Low-potency topical steroids co-formulated with other topicals that may affect the presentation of psoriasis are not permitted. Bland emollients (defined as emollients containing only ingredients that are pharmacologically inactive for the treatment of psoriasis) are allowed on all body regions but should not be used within 24 hours before any study visit.
13. Part A: Prohibited Psoriasis Treatments Exclusions: For the below prohibited psoriasis treatments, the washout period prior to Day 1 is within the time frame indicated or 5 half-lives, whichever is longer.13.Subject has used any systemic nonbiologic treatment that could affect psoriasis presentation (including oral, intravenous, intramuscular, intra-articular, intrathecal, or intralesional corticosteroids; oral retinoids; immunosuppressive/immunomodulating medication; methotrexate; azathioprine; 6-thioguanidine; mercaptopurine; mycophenolate mofetil; hydroxyurea; cyclosporine; 1,25-dihydroxyvitamin D3 analogues; psoralens; sulfasalazine; fumaric acid derivatives; JAK inhibitors; apremilast) within 4 weeks prior to Day 1. Note: Intranasal corticosteroids, inhaled corticosteroids, and eye and ear drops containing corticosteroids are permitted.
14. Part A: Prohibited Psoriasis Treatments Exclusions: For the below prohibited psoriasis treatments, the washout period prior to Day 1 is within the time frame indicated or 5 half-lives, whichever is longer.14.Subject has used leflunomide within 6 months prior to Day 1.
15. Part A: Prohibited Psoriasis Treatments Exclusions:For the below prohibited psoriasis treatments, the washout period prior to Day 1 is within the time frame indicated or 5 half-lives, whichever is longer.15.Subject has received phototherapy (including ultraviolet B, psoralen and ultraviolet A, tanning beds, therapeutic sunbathing) or excimer laser within 4 weeks prior to Day 1.
16. Part A: Prohibited Psoriasis Treatments Exclusions:For the below prohibited psoriasis treatments, the washout period prior to Day 1 is within the time frame indicated or 5 half-lives, whichever is longer.16.Subject has used botanical preparations (eg, herbal supplements or traditional medicines, including traditional Chinese medicines derived from plants, minerals, or animals) intended to treat psoriasis or other immunological diseases within 4 weeks prior to Day 1.
17. Part A: Prohibited Psoriasis Treatments Exclusions:For the below prohibited psoriasis treatments, the washout period prior to Day 1 is within the time frame indicated or 5 half-lives, whichever is longer.17.Subject has any previous exposure to TAK-279 (also known as NDI-034858) or other TYK2 inhibitors, including deucravacitinib, or subject participated in any study that included a TYK2 inhibitor (eg, deucravacitinib, VTX958, GLPG3667, etc.), unless subject has documentation of post-trial unblinding that confirms that subject did not receive a TYK2 inhibitor.
18. Part A: 18. Subject has received lithium, antimalarials, or intramuscular gold therapy within 4 weeks prior to Day 1.
19. Part A: 19. Subject is currently being treated with strong or moderate CYP3A4 inhibitors (such as itraconazole) or strong or moderate CYP3A4 inducers (such as rifampin, carbamazepine, or phenytoin), or has received strong or moderate CYP3A4 inhibitors or strong or moderate CYP3A4 inducers within 4 weeks or 5 half-lives of the inducer or inhibitor, whichever is longer, prior to Day 1, or is anticipated to require treatment with strong or moderate CYP3A4 inducers or inhibitors during the trial period (Appendix 1). Note: This includes consumption of food or beverages containing grapefruit and/or Seville oranges within 1 week of Day 1. Subjects must be counseled to avoid food or beverages containing grapefruit and/or Seville oranges for the duration of the study.
20. Part A: 20. Subject is currently being treated with oral anti-histamines for any reason, with the exception of oral anti-histamines that are stably administered at the same dose for at least 4 weeks prior to Day 1. Note: Additional treatment with oral anti-histamines may be permitted after discussion with the medical monitor.
21. Part A: Other Prohibited Concomitant Medications Exclusions: 21.Subject has received any live-attenuated vaccine within 60 days prior to Day 1 or plans to receive a live-attenuated vaccine during the study and up to 4 weeks after the last study drug administration. Note: Non–live-attenuated vaccines or boosters for coronavirus disease 2019 (COVID-19) or influenza are permitted during the study.
22. Part A: Other Prohibited Concomitant Medications Exclusions: 22.Subject received an investigational antibody or biologic therapy within 6 months prior to Day 1.
23. Part A: Other Prohibited Concomitant Medications Exclusions: 23.Subject received an investigational oral therapy within 3 months prior to Day 1
24. Part A: Other Prohibited Concomitant Medications Exclusions: 24.Subject is currently receiving a nonbiological study drug or device or has received one within 4 weeks prior to Day 1.
25. Part A: Other Prohibited Concomitant Medications Exclusions: 25.Subject is currently enrolled in a clinical trial or anticipates enrollment in a clinical trial during the course of the study.
26. Part A: Laboratory/Physical Exclusions: 26.Subject has any of the following laboratory values at the screening visit: a)Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) values ˃3 times the ULN. b)Total bilirubin (unconjugated and/or conjugated) ˃1.5 times the ULN. c)Hemoglobin <9.0 g/dL (<90.0 g/L). d)Absolute white blood cell count <3.0 × 109/L (<3000/mm3). e)Absolute neutrophil count of <1.0 × 109/L (<1000/mm3). f)Absolute lymphocyte count of <0.5 × 109/L (<500/mm3). g)Platelet count <100 × 109/L (<100,000/mm3). h)Thyroid-stimulating hormone outside the normal reference range AND free thyroxine (T4) or triiodothyronine (T3) outside the normal reference range. i)Estimated creatinine clearance <45 mL/min based on the Cockcroft-Gault calculation. j)CPK > ULN. CPK may be repeated once; if repeat value is CTCAE Grade 1 or lower (or ≤2.5 × ULN) and no higher than the initial value, subject remains eligible. Investigators should assess the subject for modulating factors including concomitant medications or vigorous exercise that may affect CPK levels.
27. Part A: Laboratory/Physical Exclusions: 27.Subject has any other significant laboratory abnormalities that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study.
28. Part A: Laboratory/ Physical Exclusions: 28.Subject does not tolerate venipuncture or inability to be venipunctured.
29. Part A: Allergies and Adverse Drug Reactions Exclusions:29.Subject has history of significant drug allergy (such as anaphylaxis).
30. Part A: Allergies and Adverse Drug Reactions Exclusions: 30.Subject has a known or suspected allergy to TAK-279 or any of its components.
31. Part A: Other Exclusions: 31.Subject has a positive pregnancy test result or plans to become pregnant during the study period, or subject is pregnant or lactating/nursing.
32. Part A: Other Exclusions: 32.Subjects who have given greater than 500 mL of blood or plasma within 30 days of screening (during a clinical trial or at a blood bank donation) or plans to donate blood during the course of the study.
33. Part A: Other Exclusions: 33.Subject is compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness, or is committed to an institution (eg, prison) by virtue of an order issued either by judicial or administrative authorities.
34. Part A: Other Exclusions: 34.Subject is a study site employee, an immediate family member (eg, spouse, parent, child, sibling), or is in a dependent relationship with study site employee who is involved in the conduct of this study, or may consent under duress.
35. Part A: Other Exclusions: 35.In Germany, subject is incapable of giving consent or otherwise meets criteria in Sections 136 or 137 of the Verordnung zum Schutz vor der schädlichen Wirkung ionisierender Strahlung - Strahlenschutzverordnung.
36. Part B: Prior Study-Related Exclusions: 1.Subject completed the parent study or Part A but was permanently discontinued from treatment.
37. Part B: Prior Study-Related Exclusions: 2.Subject had evidence of significant noncompliance with study visits or study drug in the parent study or Part A, as defined in the parent study protocol or in the opinion of the investigator.
38. Part B: Prior Study-Related Exclusions: 3.Subject met criteria for termination from the parent study or Part A, regardless of whether or not the subject was terminated from the parent study or Part A.
39. Part B: Target Disease-Related Exclusions: 4.Subject has developed evidence of non-plaque psoriasis (erythrodermic, pustular, predominantly guttate psoriasis, predominantly inverse, or drug-induced psoriasis) since enrollment in the parent study or Part A.
40. Part B: Target Disease-Related Exclusions: 5.Subject will require systemic treatment, other than nonsteroidal anti-inflammatory drugs, during the study period for an immune-related disease (eg, inflammatory bowel disease).
41. Part B: Target Disease- Related Exclusions: 6.Subject is not willing to minimize natural and artificial sunlight exposure during the study period. Use of sunscreen products and protective apparel is recommended when sun exposure cannot be avoided.
42. Part B: Target Disease- Related Exclusions: 7.Subject has developed a concomitant comorbid skin condition that, in the opinion of the investigator, would interfere with the study assessments.
43. Part B: Recent/Concurrent Infectious Disease Exclusions: 8.TB: a)Subject has signs or symptoms of active TB (including but not limited to chronic fever, chronic productive cough, night sweats, or weight loss) as judged by the investigator. b)Subject has evidence of LTBI as evidenced by a positive QFT result OR 2 indeterminate QFT results and subject does not have documentation of appropriate LTBI treatment. Note: Subjects with history of LTBI who have documentation of no history of active TB AND documentation of prior and complete treatment for LTBI are eligible. Such subjects are not required to repeat TB testing at the time of enrollment in this study as long as they continue to have no evidence of active TB; note: all other subjects (ie those with no evidence of LTBI at entrance to the parent studies or Part A) must be screened for LTBI prior to inclusion in Part B. In the EU/EEA and UK, subjects with evidence of LTBI, regardless of prophylaxis treatment status, must receive approval to participate in the study from an infectious disease or other TB specialist (eg, pulmonologist), taking into account any changes in medical or other history since initial assessment at entrance to the parent trials or Part A.
44. Part B: Recent/Concurrent Infectious Disease Exclusions: 9.Non-herpetic viral diseases a)Subject has presence of hepatitis C virus (HCV) antibody and a positive confirmatory test result for HCV RNA (nucleic acid test or polymerase chain reaction), or subject has a history of positive HCV antibody but was previously HCV RNA-negative but now has detectable HCV RNA by PCR testing. Note: Investigators should repeat HCV RNA PCR testing at assessment of eligibility for all subjects with presence of HCV antibody at screening for parent study or Part A, and should repeat anti-HCV Ab testing for subjects with negative anti-HCV Ab testing at screening for parent study or Part A but in whom risk assessment suggests an increased risk of hepatitis C. In the EU/EEA and UK, if the subject has total anti-HCV Ab positivity at screening for parent study or Part A or at assessment of eligibility for Part B but is confirmed to have no detectable HCV RNA by PCR testing, HCV RNA PCR testing will be assessed every 3 months until end of trial. b)Subject has presence of positive hepatitis B surface antigen (HBsAg+) or indeterminate hepatitis B surface antigen, presence of hepatitis B virus DNA (regardless of serology), or positive anti-hepatitis B core antibody without concurrent positive hepatitis B surface antibody (HBcAb+ and HBsAb-). Note: Investigators should repeat HBV B surface antigen and HBV DNA PCR for all subjects with anti-HBc Ab positivity, or isolated anti HBs Ab positivity without documented evidence of HBV vaccination series, at screening for parent study or Part, at eligibility assessment for Part B. HBV testing should also be repeated in any subject with no positive HBV serology in whom risk assessment suggests an increased risk of HBV. In the EU/EEA and UK, if the subject has total anti-HBc Ab positivity at screening but is confirmed to have no detectable HBV DNA by PCR testing, the subject will repeat HBV DNA PCR testing every 3 months until the end of trial; if a subject has anti-HBs Ab positivity at screening but is confirmed to have no detectable HBV DNA by PCR testing, unless the subject has documented completion of the HBV vaccination series by medical records, the subject will repeat HBV DNA PCR testing every 3 months until the end of trial. c)Subject has positive results for HIV by serology, regardless of viral load.
45. Part B: Infectious Disorder-related Exclusionss: 10.Subject developed any of the following during the parent study or Part A: a)Serious herpetic infection including any episode of disseminated disease, multidermatomal herpes zoster, herpes encephalitis, ophthalmic herpes, or multiple episodes of herpes zoster. b)Hepatitis B, hepatitis C, or HIV c)An opportunistic infection (eg, Pneumocystis jirovecii pneumonia, histoplasmosis, coccidiomycosis) d)Two occurrences of serious infection. e)A single serious infection that, in the opinion of the investigator, precludes participation in the study.
46. Part B: Noninfectious Disorders Exclusions:11.Subject developed any new clinically significant medical condition, evidence of an unstable clinical condition (eg, cardiovascular, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, or immunologic), or vital signs/physical/laboratory/ECG abnormality that would, in the opinion of the investigator, put the subject at undue risk or interfere with interpretation of study results.
47. Part B: Noninfectious Disorders Exclusions:12.Subject experienced a cardiovascular event (including but not limited to acute coronary syndrome, cerebrovascular event, myocardial infarction, deep vein thrombosis, or pulmonary embolism) or a cardiac hospitalization (coronary stenting or aortocoronary bypass surgery) during the parent study or Part A. If the subject experienced any other cardiovascular events (including but not limited to new atrial fibrillation or atrial fibrillation with rapid ventricular response or other dysrhythmia, pulmonary embolism, or deep venous thrombosis) during the parent study or Part A, in the EU/EEA and UK, the subject may only enter Part B under the condition that the investigator document an updated favorable risk-benefit assessment to justify the subject's inclusion in the study, taking into account any changes since initial assessment.
48. Part B: Noninfectious Disorders Exclusions:13.Subject has a new diagnosis of cancer or lymphoproliferative disease. An exception is made for localized nonmelanoma skin cancer (NMSC) or carcinoma in situ of the cervix; in the EU/EEA and UK, the investigator must document an updated favorable benefit-risk assessment to justify the subject’s inclusion in the study. Additionally, if the NMSC or carcinoma in situ of the cervix was diagnosed during the parent study or Part A, the investigator must continue to ascertain that there are no suitable treatment alternatives available for the participant, and that the participant has received appropriate treatment per local guideline, and that participation in Part B is appropriate in the investigator’s opinion. In the EU/EEA and UK, regardless of timing of diagnosis, the investigator must document an updated favorable benefit-risk assessment to justify the subject’s inclusion in the study, taking into account any changes since initial assessment.
49. Part B: Noninfectious Disorders Exclusions: 14.Subject has a major surgery planned during the study.
50. Part B: Noninfectious Disorders Exclusions: 15.Subject has significant/uncontrolled psychiatric illness, in the opinion of the investigator.
51. Part B: Noninfectious Disorders Exclusions: 16.Subject has any lifetime history of suicidal ideation, suicidal behavior, or suicidal attempts by 1) medical history; or 2) by C-SSRS documentation or by answering “yes” to Question 5 for suicidal ideation on the C-SSRS (Note: C-SSRS documentation assessment is not applicable for subjects rolling over from TAK-279-PsO-3004 study); or 3) is clinically deemed to have a suicide risk by the investigator.
52. Part B: Noninfectious Disorders Exclusions: 17.Subject has a PHQ-8 score of 15 or above. Note: PHQ-8 documentation assessment is not applicable for subjects rolling over from TAK-279-PsO-3004 study, however, these subjects shall be excluded if clinically deemed to have risk of clinical depression, in the opinion of the investigator.
53. Part B: Noninfectious Disorders Exclusions: 18.Subject had a history of clinically significant drug or alcohol abuse during the parent study or Part A.
54. Part B: Prohibited Psoriasis Treatments Exclusions: 19.Subject received a prohibited psoriasis treatment (see Section 6.6.2) during the parent study or Part A, whether or not that treatment was documented as a concomitant medication, and is expected to continue that treatment.
55. Part B: Laboratory/Physical Exclusions: 20.Subject has any of the following laboratory values at most recent visit from parent study or Part A (typically Week 48 for TAK-279-3001, Week 56 for TAK-279-3002, or Week 12 for TAK-279-PsO-3004, and Week 40 for Part A*): a)AST or ALT values 3 times the ULN. b)Total bilirubin (unconjugated and/or conjugated) 1.5 times the ULN. c)Hemoglobin <9.0 g/dL (<90.0 g/L). d)Absolute white blood cell count <3.0 × 109/L (<3000/mm3). e)Absolute neutrophil count of <1.0 × 109/L (<1000/mm3). f)Absolute lymphocyte count of <0.5 × 109/L (<500/mm3). g)Platelet count <100 × 109/L (<100,000/mm3). h)Thyroid-stimulating hormone outside the normal reference range AND free T4 or T3 outside the normal reference range. i)Estimated creatinine clearance <45 mL/min based on the Cockcroft-Gault calculation. j)CPK > ULN. CPK may be repeated once; if repeat value is CTCAE Grade 1 or lower (or ≤2.5 × ULN), subject remains eligible. Investigators should assess the subject for modulating factors including concomitant medications or vigorous exercise that may affect CPK levels. * Note: If between laboratory assessment and initiation of Part B there is concern that any laboratory values may have changed in a clinically meaningful way, in the opinion of the investigator, they should be repeated.
56. Part B: Laboratory/Physical Exclusions: 21.Subject has any other significant laboratory abnormalities at most recent visit that, in the opinion of the investigator, might place the subject at unacceptable risk for participation in this study.
57. Part B: Laboratory/Physical Exclusions: 22.Subject does not tolerate venipuncture or inability to be venipunctured.
58. Part B: Allergies and Adverse Drug Reactions Exclusions: 23.Subject has history of significant drug allergy (such as anaphylaxis).
59. Part B: Allergies and Adverse Drug Reactions Exclusions: 24. Subject has a known or suspected allergy to TAK-279 or any of its components.
60. Part B: Other Exclusions: 25.Subject has a positive pregnancy test result or plans to become pregnant during the study period.
61. Part B: Other Exclusions: 26.Subject is compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness, or is committed to an institution (eg, prison) by virtue of an order issued either by judicial or administrative authorities.
62. Part B: Other Exclusions: 27.Subject is a study site employee, an immediate family member (eg, spouse, parent, child, sibling), or is in a dependent relationship with study site employee who is involved in the conduct of this study, or may consent under duress.
63. Part B: Other Exclusions:28.In Germany, subject is incapable of giving consent or otherwise meets criteria in Sections 136 or 137 of the Verordnung zum Schutz vor der schädlichen Wirkung ionisierender Strahlung – Strahlenschutzverordnung.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence of treatment-emergent adverses events (TEAEs)
2. Incidence of serious adverse events (SAEs)

Secondary endpoints 2

1. Over the duration of the study: ≥75% improvement in Psoriasis Area and Severity Index (PASI-75)
2. Over the duration of the study: Static Physician Global Assessment (sPGA) of clear (0) or almost clear (1) with a ≥2-point decrease from baseline

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Takeda Development Center Americas Inc.

Sponsor organisation

Takeda Development Center Americas Inc.

Address

500 Kendall Street

City

Cambridge

Postcode

02142-1108

Country

United States

Scientific contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Takeda

Public contact point

Organisation

Takeda Development Center Americas Inc.

Contact name

Takeda

Third parties 13

Locations

9 EU/EEA countries · 106 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 123 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

14 submissions — initial application plus substantial / non-substantial modifications