moderate to severe chronic plaque psoriasis
Conditions
Sponsors
Sun Pharma Advanced Research Company Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject must have met all the criteria listed below to participate in the study. - Subject must be 6 to 15 Kg. - Diagnosis of predominantly plaque psoriasis for > or =6 months (as determined by subject interview and confirmation of diagnosis through physical examination by investigator). - Moderate to severe psoriasis at baseline defined as : - At least 10% Body Surface Area (BSA) involvement - PGA score > or = 3 - PASI score > or = 12 - Subject must be considered a candidate for systemic therapy, meaning psoriasis inadequately controlled by topical treatments (corticosteroids), and/or phototherapy, and/or previous systemic therapy - Subject is considered to be eligible according to the following tuberculosis (TB) screening criteria: a.Has no history of untreated latent or active TB prior to screening. Prophylactic treatment for latent TB (as per local guidelines) must be initiated at least 4 weeks prior to first administration of study medication. b. Has no signs or symptoms suggestive of active TB upon medical history and/or physical examination. c. Has had no recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB at least 4 weeks prior to the first administration of study medication. d. Within 4 weeks prior to first administration of study medication, either has negative diagnostic TB test results (defined as a negative tuberculin skin test ) or a negative QuantiFERON-TB Gold test. e. A subject who has a positive intradermal skin test or positive QuantiFERON-TB Gold test, or who has had recent close contact with a person with active TB, or has signs or symptoms suggestive of active TB upon medical history and/or physical examination, or if required by local guidelines or regulations as part of routine TB screening, must have a negative chest radiograph (both posterior-anterior and lateral views) or chest computed tomography (CT) scan taken within 4 weeks prior to first administration of study medication. The radiograph or scan must be read by a qualified radiologist, and must have no evidence of current active TB or old inactive TB. (Note: If either the tuberculin skin or QuantiFERON-TB Gold test is positive, and the chest radiograph or chest CT scan is negative, the subject is considered to have latent TB infection [LTBI]. Subjects with LTBI may be included if they receive prophylactic treatment for latent TB or have previously completed an adequate course of prophylactic treatment according to local guidelines or regulations without subsequent new exposure to active TB. The investigator is strongly encouraged to consider referral to a TB specialist to assess the need for repeat of prophylactic therapy if there is a history of new exposure to active TB subsequent to completion of prior treatment for LTBI or if prior treatment of LTBI was completed more than 3 months prior to screening.) -A maximum of 2 QuantiFERON tests will be allowed. A re-test is only permitted if the first is indeterminate; the result of the second test will then be used. - 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
Exclusion criteria
Exclusion criteria: 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. - Subject has laboratory abnormalities at screening including any of the following: a) Alanine transaminase (ALT) or aspartate transaminase (AST) > or =2X the upper limit of normal b) Creatinine > or =1.5X the upper limit of normal c) serum direct bilirubin > or =1.5 mg/dL d) white blood cell count or =160 mmHg and/or diastolic blood pressure of > o = 100 mmHg at Screening), or has uncontrolled diabetes. - 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 an immunomodulatory therapy in the judgment of the investigator. - The subject or a family member is among the personnel of the investigational site or sponsor/designee staff directly involved with this trial. - Any concomitant medical condition which in the opinion of the investigator could affe
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A: Pharmacokinetics (PK) Component To characterize PK and safety of tildrakizumab in pediatric subjects during a 16-week treatment period in support of final pediatric dose selection. Part B: Randomized Trial Component 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 “almost clear” with at least a 2 grade reduction from baseline at Week 12 compared to placebo.;Secondary Objective: Assess efficacy of tildrakizumab compared to placebo as measured by the proportion of subjects achieving PASI 75 & PGA score of “clear” or “almost clear” with at least a 2 grade reduction. Assess efficacy of tildrakizumab compared to placebo as measured by the proportion of subjects achieving PASI 50, PASI 90, & PASI 100. Assess changes in quality of life with the use of tildrakizumab for the treatment of moderate-to-severe chronic plaque psoriasis as measured by Children’s Dermatology Life Quality Index. Assess long-term safety & tolerability. Evaluate immunogenicity. Assess percent of subjects with severe infections or any infection requiring IV antibiotics whether or not reported as a serious event as per the regulatory definition. Assess percent of subjects with malignancies. Assess percent of subjects with confirmed MACE. Assess percent of subjects with drug-related hypersensitivity reactions.;Primary end point(s): The co-primary endpoints of PASI 75 response rate and the proportion of subjects with PGA of "clear" or "minimal" with at least a 2 grade reduction from baseline at Week 12 will be analyzed using Fisher’s exact test for comparison between treatment groups. Subjects with missing data will be treated as non-responders.;Ti | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The key secondary efficacy endpoints of PASI50, PASI90, PASI100 response rates, BSA, and CDLQI will be summarized across all time points with descriptive statistics. For all PASI responses, comparison between treatment groups will be analyzed using Fisher’s exact test. BSA and DLQI will be analyzed between treatment groups using continuous methods. More detailed descriptions of these analyses will be presented in the Statistical Analysis Plan. If at least one of the tests on the primary efficacy endpoints is significant, the subsequent tests on these five key secondary endpoints will be done in a stepdown manner to preserve the experimentwise error rate. The order of testing will be PASI90, PASI100, PASI50, CDLQI, and BSA.;Timepoint(s) of evaluation of this end point: Week 12 | — |
Countries
France, Hungary, Poland, Spain
Contacts
Public ContactClinical Development
Sun Pharmaceuticals Global
Outcome results
None listed