Efficacy and safety of brodalumab in adolescents with psoriasis – 1396
Research type
Research Study
Full title
A phase 3, randomised, double-blind, multi-centre trial to evaluate the efficacy, safety, and tolerability of brodalumab treatment compared to placebo (blinded) and ustekinumab (open-label) in adolescent subjects (12–17 years of age) with moderate-to-severe plaque psoriasis
IRAS ID
277632
Contact name
Ellen Colling
Contact email
Sponsor organisation
Pharm Research Associates (UK) Limited)
Eudract number
2019-001868-30
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Research Summary
Psoriasis is a chronic immune-mediated inflammatory skin disease occurring in around 2% of the population worldwide, and 0.7 - 1.2% of children younger than 18. Plaque psoriasis is characterised as raised, scaly and red skin lesions (plaques) usually on the scalp, elbows, knees and sacrum, which can be painful and itchy.
Current treatments in childhood include topical emollients and corticosteroids, however around 8% of adolescents, usually those with severe disease, require systemic therapies.
In psoriasis patients, an immune response is activated. IL-17 is a human protein involved in immune and inflammatory responses, raised levels of which are found in psoriatic plaques. Brodalumab is a human antibody, a type of systemic biological drug, which binds to a receptor of this protein (IL-17RA). This blocks the IL-17 pathway and in turn interrupts the inflammatory process of psoriasis, which may improve or clear the symptoms. Brodalumab is approved in the EU for treatment of adults with moderate to severe psoriasis.
The primary objective of this randomised, double-blinded (until week 12) trial is to demonstrate that brodalumab provides more effective control of psoriasis than placebo. The trial will evaluate the percentage of subjects achieving 75% reduction in a psoriasis specific severity index at Week 12. Secondary endpoints include evaluating the efficacy and safety of brodalumab compared to Ustekinumab (a standard of care treatment). Efficacy assessments are performed by a blinded assessor throughout the trial.
The trial consists of a 2-4 weeks screening period, 12 week induction, 40 week maintenance and 8 week safety follow-up. Patients will be initially randomised to one of 4 arms, brodalumab, ustekinumab or 1 of 2 placebo arms. At 12 weeks, patients randomised to brodalumab or ustekinumab will continue on maintenance treatment until week 52. Patients initially randomised to placebo will switch to either brodalumab or ustekinumab at Week 12
Summary of Results
Initially, this study was designed as a clinical phase 3, multi-centre, randomised, placebo-controlled (double-blind until Week 12), and comparator-controlled (open-label ustekinumab) trial in which adolescents (12 to 17 years of age) with moderate-to-severe plaque psoriasis were treated with brodalumab, ustekinumab, and placebo followed by brodalumab, or placebo followed by ustekinumab. This study was terminated early due to low recruitment and the availability of other treatment options as agreed with the PDCO. It was anticipated that approximately 120 participants at approximately 75 sites in Europe would be randomised in a 2:2:1:1 ratio. The actual number of participants enrolled in Europe was 12.
Planned duration was 52 weeks including a 12-week induction period and a 40-week maintenance period. At the time of early termination, the subject who had been in the study for the longest had reached the Week 20 visit.
Due to early termination of the study, the only efficacy data available was a summary of Psoriasis Area Severity Index (PASI) scores by treatment arm and time point from screening to Week 20. The number of participants included at each time point decreased from Week 0 to Week 20. For this population, treatment with brodalumab for plaque psoriasis was well tolerated and no new safety concerns were identified as compared with the known safety profile of the drug.REC name
West of Scotland REC 1
REC reference
20/WS/0113
Date of REC Opinion
29 Sep 2020
REC opinion
Further Information Favourable Opinion