A Phase 2 trial to assess efficacy and safety of zasocitinib in moderate to severe hidradenitis suppurativa

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]

Decision date (initial)

2026-03-06

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: Efficacy, Dose response, Pharmacokinetic, Safety

To evaluate the efficacy of zasocitinib compared with placebo in participants with moderate to severe hidradenitis suppurativa (HS).

Secondary objectives 1

1. To further evaluate the efficacy, safety and tolerability of zasocitinib compared with placebo in participants with moderate to severe HS.

Conditions and MedDRA coding

Hidradenitis Suppurativa

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Participants must have signs and symptoms of hidradenitis suppurativa (HS) for at least 6 months prior to screening, and a diagnosis of HS (confirmed by a dermatologist) at the screening visit with stable HS signs and symptoms for 2 months before screening.
2. Participants should have HS lesions in at least 2 distinct anatomical areas, one of which must be at least Hurley Stage II or III at both screening and Day 1.
3. Participants must have a total of ≥5 inflammatory lesions (that is, number of abscesses plus number of inflammatory nodules) at both screening and Day 1.
4. Participants must have a history of inadequate response to a previous course of oral antibiotic for treatment of HS or exhibited recurrence, intolerance, or contraindication during that course of oral antibiotic, as assessed by the principal investigator.
5. Participant is aged ≥18 years at the time of consent.
6. Participant is either a.) An individual with potential for pregnancy, who is now surgically sterile; b.) of nonchildbearing potential with laboratory confirmation of postmenopausal status OR c.) agrees to use a highly effective method of contraception from the signing of informed consent form.
7. For participants in the EU/EEA, the investigator must have no reason to believe that the participant would be placed at risk by participating in the trial.
8. Participant is willing and able to understand and fully comply with all trial procedures and requirements (including the use of digital tools and applications), in the opinion of the investigator.
9. Participant has provided written informed consent and any required privacy authorization before the initiation of any trial procedures.

Exclusion criteria 21

1. Participant has a draining tunnel count of >20 at screening or Day 1.
2. Participant has any other active skin disease or condition (for example, bacterial cellulitis, Candida intertrigo, extensive condyloma) that may, in the opinion of the investigator, interfere with the assessment of HS or participant has developed a concomitant comorbid skin condition that, in the opinion of the investigator, would interfere with the trial assessments.
3. Participant has a diagnosis of sarcoidosis, systemic lupus erythematosus, or active inflammatory bowel disease.
4. Participant has a diagnosis of inflammatory conditions other than HS, including but not limited to, psoriasis, psoriatic arthritis, and rheumatoid arthritis.
5. Tuberculosis (TB): a) Participants have a history of active TB infection, regardless of treatment status. b) Participants have 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) Participants have evidence of latent tuberculosis infection (LTBI) as evidenced by a positive QuantiFERON (QFT) result OR 2 indeterminate QFT results, and participant does not have documentation of appropriate LTBI prophylaxis or is not able or not willing to initiate appropriate LTBI prophylaxis. Participant remains eligible if there are no signs/symptoms of active TB AND documentation of no history of active TB can be provided AND (1) participant can provide documentation of prior and complete treatment for LTBI (appropriate in duration and type per current local country guidelines) or (2) participant 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, participants with evidence of LTBI, regardless of prophylaxis treatment status, must receive approval to participate in the trial from an infectious disease or other TB specialist (for example, pulmonologist). Note: TB prophylaxis regimens should be administered according to local guidelines; however, because of potential interactions with zasocitinib, rifampin should not be used. For isoniazid monotherapy, a minimum of 6 months should be used. TB testing should be conducted using QFT-TB Gold submitted to the central laboratory unless alternate or additional tests are required per local guidelines. See Appendix 13.4 for country-specific requirements. d) Participant has had any imaging trial 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 participants regardless of QFT-TB Gold results unless the participant has had normal chest imaging in the 6 months prior to screening.
6. Herpes infections: a) Participant 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) Participant 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. Nonherpetic viral diseases: a) Participant has presence of hepatitis C virus (HCV) antibody and a positive confirmatory test result for HCV RNA (nucleic acid test or polymerase chain reaction [PCR]). In the EU/EEA, if the participant has total anti-HCV antibody 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 (EOT). b) Participant has presence of positive hepatitis B virus surface antigen (HBsAg), or indeterminate HBsAg, presence of HBV DNA (regardless of serology), or positive anti-hepatitis B core antibody (HBcAb) without concurrent positive HBsAb (HBcAb+ and HBsAb-). In the EU/EEA, if the participant has total anti-HBc antibody positivity at screening but is confirmed to have no detectable HBV DNA by PCR testing, the participant will repeat HBV DNA PCR testing every 3 months until the EOT; if a participant has anti-HBsAb positivity at screening but is confirmed to have no detectable HBV DNA by PCR testing, unless the participant has documented completion of the HBV vaccination series by medical history, the participant will repeat HBV DNA PCR testing every 3 months until the EOT. Note: For other countries in which there are hepatitis B screening guidelines, these can be done per local regulations or country standard of care. c) Participant has positive results for HIV by serology, regardless of viral load.
8. Other infectious diseases: a) Participant has a history of active infection or febrile illness within 10 days prior to Day 1, as assessed by the investigator. b) Participant has a history of symptoms suggestive of systemic or invasive infection within 30 days prior to Day 1. c) Participant has a history of bacterial, viral, or fungal infection that required hospitalization or treatment with intravenous (IV) antimicrobial therapy within 8 weeks prior to Day 1, or oral antimicrobial therapy within 30 days prior to Day 1. d) Participant 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 (except those part of the HS clinical findings)/infections or fungal infections (except ungual onychomycosis). e) Participant 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) Participant has a history of opportunistic infections (for example, Pneumocystis jirovecii pneumonia, histoplasmosis, or coccidiomycosis). g) Participant had a bacterial infection within 60 days prior to Day 1 for which he or she did not receive treatment.
9. Participant has any clinically significant medical condition, evidence of an unstable clinical condition (for example, cardiovascular, renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, neurologic, nutritional, ophthalmologic, or immunologic), or vital signs/physical/laboratory/electrocardiogram (ECG) abnormality that would, in the opinion of the investigator, put the participant at undue risk or interfere with interpretation of trial results. These include but are not limited to: For full list please refer to the Protocol.
10. Participant has ECG abnormalities that are considered clinically significant and would pose an unacceptable risk to the participant if they participated in the trial, in the opinion of the investigator.
11. Participant has inadequate renal, hepatic, or pancreatic function before enrollment based on the following parameters: a) Total bilirubin (unconjugated and/or conjugated) >1.5 × upper limit of the normal range (ULN) unless the participant has known Gilbert’s syndrome that can explain the elevation of bilirubin, or b) Serum ALT or AST >3 × ULN, or c) Creatinine >1.5 × ULN. Note: The participant may be retested (1 time) to meet eligibility criteria at the discretion of the investigator. d) Estimated creatinine clearance <45 mL/min based on the Cockcroft-Gault calculation. e) A history of chronic pancreatitis or recent acute pancreatitis (<60 days/not fully resolved).
12. Participant has any of the following laboratory values at the screening visit: a) Hemoglobin <9.0 g/dL (<90.0 g/L). b) Absolute white blood cell count <3.0 × 109/L (<3000/mm3). c) Absolute neutrophil count (ANC) of <1.0 × 109/L (<1000/mm3). d) Absolute lymphocyte count of <0.5 × 109/L (<500/mm3). e) Platelet count <100 × 109/L (<100,000/mm3). f) Thyroid-stimulating hormone (TSH) (>10 mIU/L) or free T4 or T3 outside the normal reference range. Note: Participants would be allowed to rescreen after treatment. g) Triglyceride level ≥750 mg/dL (≥8.5 mmol/L). h) Creatine phosphokinase (CPK) > ULN. CPK may be repeated once; if repeat value is Common Terminology Criteria for Adverse Events (National Cancer Institute) (CTCAE) Grade 1 or lower (or ≤2.5 × ULN) and no higher than the initial value, participant remains eligible. Investigators should assess the participant for modulating factors including concomitant medications or vigorous exercise that may affect CPK levels. i) Participant has any other significant laboratory abnormalities that, in the opinion of the investigator, might place the participant at unacceptable risk for participation in this trial. j) Participant does not tolerate venipuncture or inability to be venipunctured.
13. Participant has a history of significant drug allergy (such as anaphylaxis), or Participant has a known or suspected allergy to zasocitinib or any of its components.
14. Participant has a positive pregnancy test result or plans to become pregnant during the trial period, including plans to donate ova (eggs) or sperm, or participant is pregnant or lactating/nursing.
15. Participant has a history of substance abuse within 12 months prior to Day 1.
16. Participants who have given greater than 500 mL of blood or plasma within 30 days prior to screening (during a clinical trial or at a blood bank donation) or plan to donate blood during the course of the trial.
17. Participant is compulsorily detained for treatment of either a psychiatric or physical (for example, infectious disease) illness, or is committed to an institution (for example, prison) by virtue of an order issued either by judicial or administrative authorities.
18. Participant is a trial site employee, an immediate family member (for example, spouse, parent, child, sibling), or is in a dependent relationship with trial site employee who is involved in the conduct of this trial or may consent under duress.
19. In Germany, participant 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.
20. Participants with a history of malignancy within the past 5 years prior to the screening visit are excluded, EXCEPT if the malignancy was a cutaneous squamous or basal cell carcinoma, or in situ cervical cancer that has been successfully treated and is considered cured; in the EU/EEA, investigators must document a favorable benefit-risk assessment.
21. History or current status of substance use disorder and or tobacco use disorder. For participants with excessive alcohol intake or 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 participant’s inclusion in the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Hidradenitis Suppurativa Clinical Response 75 (HiSCR75) at Week 16, assessed as proportion of participants who achieve HiSCR75 at Week 16. Hidradenitis Suppurativa Clinical Response 75 is defined as at least a 75% reduction in the total abscess and inflammatory nodule (AN) count with no increase in abscess or draining tunnel count relative to baseline.

Secondary endpoints 2

1. HiSCR50 at Week 16, assessed as proportion of participants who achieve HiSCR50 at Week 16.
2. Incidence of treatment emergent adverse events (TEAEs) throughout the trial.

Investigational products

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

Test 1

Placebo 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 16

Locations

4 EU/EEA countries · 14 investigational sites

By country

Investigational sites

Results and documents

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

Documents 47 files

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

Application history

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