A Study of Tildrakizumab in Pediatric Subjects With Chronic Plaque Psoriasis

A Multicenter, Randomized, Placebo and Active Comparator-controlled Clinical Trial to Study the Efficacy, Safety and Pharmacokinetics (PK) of Tildrakizumab in Pediatric Subjects From 6 to <18 Years of Age With Moderate to Severe Chronic Plaque Psoriasis

The study has been designed with three components. Part A is an open label PK study followed by a randomized trial component (Part B) followed by open label Long Term Extension (LTE).

The initial PK analysis is first done in adolescent subjects (12 to <18 years) before initiating the PK study in younger cohort (6 to <12 years)

Study Overview

• Status: Recruiting
• Conditions: Moderate-to-severe Chronic Plaque Psoriasis
• Intervention / Treatment: Drug: Tildrakizumab; Drug: Tildrakizumab; Drug: Tildrakizumab; Drug: Tildrakizumab; Drug: Placebo; Drug: Etanercept; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Head, Clinical development; Phone Number: 5689 91 2266455645; Email: Clinical.Trial@sunpharma.com

Study Locations

• Hungary
  • Budapest, Hungary, H-1033
    • Not yet recruiting
    • Site 63
  • Budapest, Hungary, H-1036
    • Recruiting
    • Site 62
  • Debrecen, Hungary, H-4032
    • Recruiting
    • Site 61
  • Kaposvar, Hungary, H-7400
    • Recruiting
    • Site 64
  • Szeged, Hungary, 6720
    • Withdrawn
    • Site 28
• India
  • Ahmedabad, India, 380015
    • Not yet recruiting
    • Site 70
  • Ahmedabad, India, 380009
    • Recruiting
    • Site 79
  • Chennai, India, 600004
    • Not yet recruiting
    • Site 78
  • Kolkata, India, 700058
    • Not yet recruiting
    • Site 75
  • Kolkata, India, 700073
    • Not yet recruiting
    • Site 76
  • Lucknow, India, 226005
    • Recruiting
    • Site 71
  • Pune, India, 411001
    • Not yet recruiting
    • Site 73
  • Surat, India, 395010
    • Not yet recruiting
    • Site 77
  • Surat, India, 395002
    • Recruiting
    • Site 74
  • Warangal, India, 506002
    • Recruiting
    • Site 80
• Poland
  • Bialystok, Poland, 15-453
    • Recruiting
    • Site 57
  • Gdańsk, Poland, 80-214
    • Not yet recruiting
    • Site 55
  • Katowice, Poland, 40-611
    • Recruiting
    • Site 51
  • Lodz, Poland, 90-265
    • Recruiting
    • Site 54
  • Lodz, Poland, 90-436
    • Recruiting
    • Site 56
  • Lublin, Poland, 20-573
    • Recruiting
    • Site 58
  • Ostrowiec Swietokrzyski, Poland, 27-400
    • Recruiting
    • Site 50
  • Sosnowiec, Poland, 41-200
    • Recruiting
    • Site 59
  • Szczecin, Poland, 70-332
    • Recruiting
    • Site 52
  • Warszawa, Poland, 02-507
    • Recruiting
    • Site 53
  • Wrocław, Poland, 50-566
    • Withdrawn
    • Site 40
  • Wrocław, Poland, 51-503
    • Recruiting
    • Site 39
    • Contact: Phone Number: 48 515 138 395; Email: Mateusz.machay@dermmedica.pl
  • Wrocław, Poland, 51-685
    • Recruiting
    • Site 38
    • Contact: Phone Number: 48 607 375 354; Email: zuzanna.pawlak@wromedica.pl
• Slovakia
  • Bardejov, Slovakia, 8501
    • Recruiting
    • Site 92
  • Svidnik, Slovakia, 8901
    • Recruiting
    • Site 91
  • Trnava, Slovakia, 91775
    • Not yet recruiting
    • Site 90
• Spain
  • Barcelona, Spain, 08041
    • Not yet recruiting
    • Site 41
    • Contact: Phone Number: +34 93 55 37 007; Email: lpuig@hsp.santpau.es
  • Las Palmas De Gran Canaria, Spain, 35019
    • Recruiting
    • Site 47
    • Contact: Phone Number: +34636843487; Email: anagrabasco@gmail.com
  • Madrid, Spain, 28041
    • Withdrawn
    • Site 42
  • Valencia, Spain, 46014
    • Withdrawn
    • Site 44
  • Valencia, Spain, 46940
    • Withdrawn
    • Site 45
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35244
      • Withdrawn
      • Site 23
  • California
    • Fountain Valley, California, United States, 92708
      • Recruiting
      • Site 1
      • Contact: Phone Number: 714-531-2966; Email: vanessa.firstocdermatology@gmail.com
    • Thousand Oaks, California, United States, 91320
      • Recruiting
      • Site 2
      • Contact: Phone Number: 805-298-7021; Email: clinicaltrials@calderm.net
  • Florida
    • Clearwater, Florida, United States, 33756
      • Withdrawn
      • Site 4
    • Coral Gables, Florida, United States, 33146
      • Withdrawn
      • Site 24
    • Miami, Florida, United States, 33126
      • Completed
      • Site 20
    • Miami, Florida, United States, 33173
      • Recruiting
      • Site 7
      • Contact: Phone Number: 125 305-273-7998; Email: v.diartt@skinresearchsf.com
    • Orlando, Florida, United States, 32819
      • Withdrawn
      • Site 12
  • Michigan
    • Bay City, Michigan, United States, 48706
      • Withdrawn
      • Site 5
    • Troy, Michigan, United States, 48084
      • Withdrawn
      • Site 16
  • Missouri
    • Saint Joseph, Missouri, United States, 64506
      • Withdrawn
      • Site 22
  • Texas
    • Dallas, Texas, United States, 75231
      • Withdrawn
      • Site 8
  • Utah
    • South Jordan, Utah, United States, 84095
      • Withdrawn
      • Site 10
  • Washington
    • Spokane, Washington, United States, 99202
      • Completed
      • Site 14

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject must be 6 to < 18 years of age, of either sex, of any race/ ethnicity, must weight greater than or equal to 15Kg.
• Diagnosis of predominantly plaque psoriasis for ≥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 ≥ 3, and PASI score ≥ 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 tuberculosis (TB) screening criteria
• 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.

Exclusion Criteria:

• 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: Alanine transaminase (ALT) or aspartate transaminase, (AST) ≥2X the upper limit of normal, Creatinine ≥1.5X the upper limit of normal serum direct bilirubin ≥ 1.5 mg/dL, white blood cell count < 3.0 x 103/μL, and 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
• Subject who is expected to require topical therapy, phototherapy, or additional systemic therapy for psoriasis during the trial
• Female subjects of childbearing potential who are pregnant, intend to become pregnant (within 6 months of completing the trial), or are lactating. (Sexually active adolescent girls will be required to use contraception)
• 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
• Positive human immunodeficiency virus (HIV) test result, hepatitis B surface (HBS) antigen, or hepatitis C virus (HCV) test result

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Part A; Part A is a DOSE FINDING COMPONENT: OPEN LABEL PK lead-in and safety component	Drug: Tildrakizumab; Week 0 (Day 1), Week 4 (Day 28) and week 16 (Day 112); Drug: Tildrakizumab; (Weeks 16 to 52); Drug: Tildrakizumab; at every 12 weeks in open label fashion till 5 years (240 weeks).; Drug: Tildrakizumab; (Weeks 0 to 16)
Experimental: Part B Part 1: Placebo and active comparator controlled study	Drug: Tildrakizumab; Week 0 (Day 1), Week 4 (Day 28) and week 16 (Day 112); Drug: Tildrakizumab; (Weeks 16 to 52); Drug: Tildrakizumab; at every 12 weeks in open label fashion till 5 years (240 weeks).; Drug: Tildrakizumab; (Weeks 0 to 16); Drug: Placebo; (Weeks 0 to 16); Drug: Etanercept; (Weeks 0 to 16); Drug: Placebo; (Weeks 16 to 52)
Experimental: Part B-1 and B-2: Randomized withdrawal and retreatment after relapse	Drug: Tildrakizumab; Week 0 (Day 1), Week 4 (Day 28) and week 16 (Day 112); Drug: Tildrakizumab; (Weeks 16 to 52); Drug: Tildrakizumab; at every 12 weeks in open label fashion till 5 years (240 weeks).; Drug: Tildrakizumab; (Weeks 0 to 16); Drug: Placebo; (Weeks 0 to 16); Drug: Placebo; (Weeks 16 to 52)
No Intervention: Part B 3: Efficacy and Safety Follow-up
Experimental: Part C: LTE	Drug: Tildrakizumab; Week 0 (Day 1), Week 4 (Day 28) and week 16 (Day 112); Drug: Tildrakizumab; (Weeks 16 to 52); Drug: Tildrakizumab; at every 12 weeks in open label fashion till 5 years (240 weeks).; Drug: Tildrakizumab; (Weeks 0 to 16)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part A - Maximum Plasma Concentration	Day 3, 7 and 28 following first dose
Part A - Area under the plasma concentration-time curve	Day 3, 7 and 28 following first dose
Part A - Maximum Plasma Concentration	Weeks 4,8, and 12 following second dose
Part A - Area under the plasma concentration-time curve	Weeks 4,8, and 12 following second dose
Proportion of subjects with at least 75% improvement in the PASI response from baseline	Week 12
Proportion of subjects with PGA of "clear" or "almost clear" with at least a 2 grade reduction from baseline	Week 12
Number of subjects with adverse events	Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects achieving Psoriasis Area & Severity Index (PASI) 50 from baseline		Week 12, 16, 28, 40, 52, 64, 76 and 88
Proportion of subjects achieving Psoriasis Area & Severity Index (PASI) 90 from baseline		Week 12, 16, 28, 40, 52, 64, 76 and 88
Proportion of subjects achieving Psoriasis Area & Severity Index (PASI) 100 from baseline		Week 12, 16, 28, 40, 52, 64, 76 and 88
Proportion of subjects achieving PASI 75 and PGA score of "clear" or "almost clear" with at least a 2 grade reduction from baseline		Week 16, 28, 40, 52, 64, 76 and 88
Change in quality of life as measured by Children's Dermatology Life Quality Index (CDLQI)	The CDLQI is a 10-item questionnaire that measures the impact of skin disease on children's (aged 2-15 years) quality of life. Each question was evaluated on a 4-point scale ranging from 0 (not at all) to 3 (very much); where higher scores indicate more impact on quality of life. The CDLQI total score was the sum of individual scores of question 1-10 and ranges from 0 (not at all) to 30 (very much): 0-1 = no effect at all on the children's life; 2-6 = small effect on the children's life; 7-12 = moderate effect on the children's life; 13-18 = very large effect on the children's life; 19-30 = extremely large effect on the children's life. Higher scores indicate more impact on quality of life of children.	Week 108
Number of subjects with Adverse events		Week 108
Immunogenicity - Anti-drug antibody status		Week 108
Percent of subjects with severe infections	defined as any infection meeting the regulatory definition of a serious adverse event, or any infection requiring IV antibiotics whether or not reported as a serious event as per the regulatory definition	Week 108
Percent of subjects with malignancies	including non-melanoma and melanoma skin cancer, but excluding carcinoma in situ of the cervix	Week 108
Percent of subjects with confirmed major adverse cardiovascular events	major adverse cardiovascular events	Week 108
Percent of subjects with drug- related hypersensitivity reactions	e.g. anaphylaxis, urticarial, angioedema, etc	Week 108

Other Outcome Measures

Outcome Measure	Time Frame
Relapse rates after withdrawal of treatment with tildrakizumab	Week 52
Rebound rates after withdrawal of treatment with tildrakizumab	Week 52
response to retreatment after relapse after withdrawal of treatment with tildrakizumab - Proportion of subjects with at least 75% improvement in the PASI response from baseline	Week 52
response to retreatment after relapse after withdrawal of treatment with tildrakizumab - Proportion of subjects with PGA of "clear" or "almost clear" with at least a 2 grade reduction from baseline	Week 52
Maintenance of response - Proportion of subjects with at least 75% improvement in the PASI response from baseline	Week 52
Maintenance of response - Proportion of subjects with PGA of "clear" or "almost clear" with at least a 2 grade reduction from baseline	Week 52

Collaborators and Investigators

• Sponsor: Sun Pharmaceutical Industries Limited

Study record dates

Study Major Dates

• Study Start (Actual): January 15, 2020
• Primary Completion (Estimated): May 23, 2031
• Study Completion (Estimated): July 23, 2031

Study Registration Dates

• First Submitted: June 19, 2019
• First Submitted That Met QC Criteria: June 24, 2019
• First Posted (Actual): June 25, 2019

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 15, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Etanercept; Antibodies, Monoclonal
• Other Study ID Numbers: TILD-19-12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No