Study to see how good and safe Tildrakizumab is in children aged 6 to under 18 years of age with skin patches

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Sun Pharmaceutical Industries Limited

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

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

Trial duration

29 Jul 2021 → ongoing

Decision date (initial)

2024-06-17

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Sun Pharmaceuticals Industries Limited

External identifiers

EU CT number

2023-504447-14-00

EudraCT number

2019-003551-11

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety

1) To characterize PK and safety of tildrakizumab in pediatric subjects during a 16-week treatment period in support of final pediatric dose selection.
2) To evaluate the efficacy of tildrakizumab in pediatric subjects from 6 to <18 years of age with moderate to severe chronic plaque psoriasis as measured by the proportion of subjects with at least 75% improvement in the Psoriasis Area & Severity Index (PASI75) response from baseline, and the proportion of subjects with Physician’s Global Assessment (PGA) of “clear” or “minimal” with at least a 2-grade reduction from baseline at Week 16 compared to placebo.

Secondary objectives 1

1. To evaluate the efficacy of tildrakizumab in pediatric subjects from 6 to <18 years of age with moderate to severe chronic plaque psoriasis as measured by the proportion of subjects with at least 75% improvement in the Psoriasis Area & Severity Index (PASI 75 response) from baseline, and the proportion of subjects with Physician’s Global Assessment (PGA) score of “clear” or “ minimal” with at least a 2-grade reduction from baseline at Week 12 compared to placebo.

Conditions and MedDRA coding

Treatment of pediatric subjects with moderate to severe chronic plaque psoriasis

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001451-PIP01-13

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. 1. Parts A and B A subject must have met all the criteria listed below to participate in the study. - Subject must be 6 to ≤ 17 years of age, of either sex, of any race/ ethnicity, must weigh > 15 kg at screening
2. 5. -Subject has a negative evaluation for tuberculosis (TB) within 4 weeks before initiating Investigational medicinal product (IMP), defined as a negative QuantiFERON test. Subjects with a positive or 2 successive indeterminate QuantiFERON tests are allowed if they have all of the following: - No history of active TB or symptoms of TB - A posterior-anterior (PA) chest radiogram (with associated report available at the site) performed within 3 months of Screening with no evidence of active TB (or of any other pulmonary infectious diseases), - If prior latent TB infection, must have history of adequate prophylaxis (per local standard of care), - If presence of latent TB is established, then treatment according to local country guidelines must have been followed for 4 weeks, prior to inclusion in the study. A maximum of 2 QuantiFERON tests are allowed. A re-test is only permitted if the first is indeterminate; the result of the second test will then be used.
3. 6. -Subject should have documentation of adequate, up-to-date, age-appropriate vaccination status at screening. If required, antibody titers may be checked at screening based on investigator’s discretion.
4. 7. -Subject is unlikely to conceive, as indicated by at least one yes answer to the following questions: - Subject is a male. - Subject is a female of child-bearing potential and agrees to abstain from heterosexual activity OR use a medically accepted method of contraception OR use appropriate effective contraception as per local regulations or guidelines for continued use during the study and for 6 months following administration of the last dose of the investigational medicinal product. Medically accepted methods of contraception include, but are not limited to, condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed Intra uterine Device (IUD), inert or copper-containing IUD, hormone-releasing IUD, systemic hormonal contraceptive, and surgical sterilization (e.g., hysterectomy or tubal ligation). Male subjects with female partners of childbearing potential who are not using birth control as described above must use a barrier method of contraception (e.g., condom) if not surgically sterile (i.e., vasectomy). - Subject is a surgically sterilized female or is documented to be pre- menarchal
5. 8. -For a female with childbearing potential, a negative serum pregnancy test at Screening and a negative urine pregnancy test within 24 hours prior to the first dose of study medication and at all subsequent visits as per the schedule of assessments.
6. 15. − Subject is unlikely to conceive, as indicated by at least one “yes” answer to the following questions: - Subject is male - Subject is a female of child-bearing potential and agrees to abstain from heterosexual activity OR use a medically accepted method of contraception OR use appropriate effective contraception as per local regulations or guidelines for continued use during the study and for 6 months following administration of the last dose of the investigational medicinal product. Medically accepted methods of contraception include, but are not limited to, condoms (male or female) with or without a spermicidal agent, diaphragm or cervical cap with spermicide, medically prescribed Intra uterine Device (IUD), inert or copper-containing IUD, hormone-releasing IUD, systemic hormonal contraceptive, and surgical sterilization (e.g., hysterectomy or tubal ligation). Male subjects with female partners of childbearing potential who are not using birth control as described above must use a barrier method of contraception (eg, condom) if not surgically sterile (ie, vasectomy). - Subject is a surgically sterilized female or is documented to be pre-menarchal
7. 16. − For a woman of childbearing potential, negative urine pregnancy test within 24 hours prior to the first dose of study medication for the extension study and at each subsequent visit
8. 17. − Subject must have results of clinical laboratory tests (complete blood count [CBC], blood chemistries, and urinalysis) within normal limits or clinically acceptable to the investigator prior to the first dose of study medication. Note: The Investigator is encouraged to consult with the medical monitor (or appropriate designee) if there are questions regarding the significance of any out-of-range values.
9. 18. − Subject must have results of a physical examination, including blood pressure within clinically acceptable limits to the investigator prior to the extension study's first dose of study medication for the extension study Note: The Investigator is encouraged to consult with the medical monitor (or appropriate designee) if there are questions regarding the significance of any out-of-range values.
10. 9. - Subject must have results of a physical examination within normal limits or clinically acceptable limits to the investigator prior to the first dose of study medication. The investigator is encouraged to consult with the medical monitor (or appropriate designee) if there are questions regarding the significance of any out-of-range values. Laboratory abnormalities deemed not clinically significant by the investigator should be clarified with the Contract Research Organization (CRO) or Sponsor’s Medical monitor (MM) before proceeding with the trial.
11. 12. PART C: − Willingness and ability to comply with the protocol.
12. 13. − Subject has completed at least 64 weeks of Part B of the study. Subjects rolled over from Part A to Part B to receive open label tildrakizumab and subjects initially randomized to Etanercept and receiving open label tildrakizumab in Part B, can enter LTE from Week 52 onwards.
13. 14. − Subject has PGA score of ≤ 2 at the baseline visit of Part C.
14. 10. - To participate in whole-body photography at designated sites, the subject must be willing to give assent or written informed consent and be able to adhere to dose and visit schedules. Photography will be an optional procedure for subjects to participate in the trial. Note: Whole-body photographs are being used for visual evaluation only and will not be included in any analyses. A subject unwilling to consent to any of this procedure may still be included in this trial; however, whole-body photography must not be obtained. Photography will not be applicable to Part A.
15. 2. - Diagnosis of predominantly plaque psoriasis for ≥6 months (as determined by subject interview and confirmation of diagnosis through physical examination by investigator).
16. 3. - Moderate to severe psoriasis at baseline defined as : - At least 10% body surface area (BSA) involvement - PGA score ≥ 3 - PASI score ≥ 12
17. 4. -Subject must be considered a candidate for systemic therapy and/or phototherapy
18. 11. • Willingness and ability to comply with the protocol

Exclusion criteria 28

1. 1. PART A and B - A subject meeting any of the exclusion criteria listed below must be excluded from participating in the trial: - Subject has predominantly non-plaque forms of psoriasis, specifically erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new-onset guttate psoriasis.
2. 5. - Subject with presence of any infection or history of recurrent infection requiring treatment with systemic antibiotics within 2 weeks prior to screening, or severe infection (e.g., pneumonia, cellulitis, bone or joint infections) requiring hospitalization or treatment with IV antibiotics within 8 weeks prior to Screening
3. 6. - Subject with any previous use of tildrakizumab or other IL-23/Th-17 pathway inhibitors, including p40, p19 and IL-17 antagonists for psoriasis.
4. 10. - Subject who has received live viral or bacterial vaccination within 4 weeks prior to baseline or who intends to receive live viral or bacterial vaccination during the trial. Note: If needed, an entry into the study could be deferred until such vaccination is completed and adequate time (4 weeks) has elapsed until baseline.
5. 7. - Prior use of TNF-alpha inhibitors will be allowed. However, the number of subjects with prior use of TNF-alpha inhibitors will be capped at 40% and the analysis will be stratified based on prior use of these biologics. When the number of subjects with prior use of TNF –alpha inhibitors reaches 40% of the sample size, the study population will be re-evaluated with respect to the general psoriasis population, and % cap may be revised if found necessary.
6. 8. - Positive human immunodeficiency virus (HIV) test result, hepatitis B virus (HBV) test, or hepatitis C virus (HCV) test result.
7. 9. - Prior malignancy or concurrent malignancy (excluding successfully treated basal cell carcinoma, squamous cell carcinoma of the skin in situ, squamous cell carcinoma with no evidence of recurrence within 5 years or carcinoma in situ of the cervix that has been adequately treated).
8. PART C: - A subject meeting any of the exclusion criteria listed below must be excluded from participating in the extension study: - Females of childbearing potential, who are pregnant or intend to become pregnant (within 6 months following administration of the last dose of the investigational medicinal product), or are lactating (Sexually active adolescent girls will be required to use contraception).
9. - Subject who intends to receive live viral or bacterial vaccination during the trial.
10. - Subject has any active or uncontrolled significant organ dysfunctionor clinically significant laboratory abnormalities or any condition that place, the subject at unacceptable risk for participation in a long-term trial of immunomodulatory therapy in the judgment of the Investigator.
11. - Subject who, in the opinion of the investigator, will not be able to participate optimally in the trial.
12. - Subjects who have a high risk of suicidality at the screening assessment based on the Investigator’s judgment or, if appropriate, as indicated by a response of “yes” within the last 12 months to Questions 4 or 5 in the suicidal ideation section, or any positive response in the behavioral section of the C-SSRS
13. - Subject is receiving or is anticipated to receive any of the prohibited medications, supplements, and other substances listed in Table 4 during the course of the trial
14. - Subject who is currently participating in another interventional clinical trial or has participated in an interventional clinical trial within 5 half-lives (of the drug) to wash out prior to randomization. (Subjects participating in observational studies or non-interventional registry studies may be included in the study)
15. - Subject has sustained, uncontrolled hypertension (defined as average SBP and/or DBP that is greater than or equal to the 95th percentile for sex, age, and height on three or more occasions.), or has uncontrolled diabetes.
16. - Subject has been hospitalized due to an acute cardiovascular event, illness or surgery within 6 months prior to screening
17. - Within 6 months prior to screening, any significant organ dysfunction or clinically significant laboratory abnormalities that place the subject at unacceptable risk for participation in a trial of immunomodulatory therapy are in the judgment of the investigator.
18. - The subject or a family member is among the personnel of the investigational site or sponsor/designee staff directly involved with this trial.
19. - Any concomitant medical condition that in the opinion of the Investigator could affect the trial outcome or present an unacceptable risk
20. - Subject who, in the opinion of the Investigator, will not be a reliable participant in the trial.
21. - Subject who has a history of alcohol or drug abuse in the previous year.
22. 2. - Subject has laboratory abnormalities at screening, including any of the following: a) Alanine transaminase (ALT) or aspartate transaminase (AST) ≥2X the upper limit of normal b) Creatinine ≥1.5X the upper limit of normal c) Serum direct bilirubin ≥ 1.5 mg/dL d) White blood cell count < 3.0 x 103/μL e) Any other laboratory abnormality which, in the opinion of the Investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results.
23. - Subjects with a history of psychiatric inpatient hospitalization within the past year
24. - Subjects with any other clinically significant laboratory abnormality, which, in the opinion of the Investigator, will prevent the subject from completing the study or will interfere with the interpretation of the study results
25. - History of hypersensitivity to the applicable IMP: tildrakizumab, etanercept (EU) or any ingredients of the study drug or placebo
26. 3. - Subject who is expected to require topical therapy, phototherapy, or additional systemic therapy for psoriasis during the trial.
27. 4. - Female subjects of childbearing potential who are pregnant or intend to become pregnant (within 6 months following administration of the last dose of the investigational medicinal product) or are lactating (Sexually active adolescent girls will be required to use contraception)
28. - History of hypersensitivity to tildrakizumab or any excipients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Part A • Pharmacokinetic parameters of tildrakizumab like observed maximum plasma concentration (Cmax), time to observed maximum plasma concentration in plasma (Tmax), area under the plasma concentration-time curve (AUC), half-life (T1/2), apparent volume of distribution (Vd/F) and clearance (CL).
2. Part B • The proportion of subjects with at least 75% improvement in the PASI score (PASI 75 response) from baseline at Week 16. • The proportion of subjects with PGA score of “clear” or “minimal” with at least a 2-grade reduction from baseline at Week 16.

Secondary endpoints 1

1. Please refer to the enclosed protocol for more details regarding secondary endpoints.

Investigational products

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

Test 1

Comparator 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Sun Pharmaceutical Industries Limited

Sponsor organisation

Sun Pharmaceutical Industries Limited

Address

1 Plot No 201 B, Western Express Highway, Goregaon East Western Express Highway Goregaon East

City

Mumbai

Postcode

400063

Country

India

Scientific contact point

Organisation

Sun Pharmaceutical Industries Limited

Contact name

Clinical Development

Public contact point

Organisation

Sun Pharmaceutical Industries Limited

Contact name

Clinical Development

Third parties 3

Locations

4 EU/EEA countries · 22 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 55 files

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

Application history

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