Johnson and Johnson Told to Justify Phase III Icotrokinra Trial Design Over Sample Size, Patient Exposure
New Delhi: Johnson & Johnson Pvt. Ltd. (JnJ) has been asked to justify key aspects of its proposed Phase III clinical trial protocol for Icotrokinra (JNJ-77242113) after the Subject Expert Commitee (SEC), under the Central Drugs Standard Control Organisation (CDSCO) in its meeting raised substantial concerns regarding sample size, study design and unnecessary patient exposure.
The firm made an online submission presenting phase III clinical trial protocol no. 77242113UCO3001, Amendment 1 dated 24 July 2025. After detailed deliberation, the committee opined that the proposed trial is aimed at studying the safety and efficacy of icotrokinra, an IL-23-receptor antagonist, in patients with moderate to severe ulcerative colitis.
The proposal consists of two sub-studies: (i) an induction study (12-week duration) – to evaluate efficacy in inducing disease remission, and (ii) a maintenance study (40 weeks – after the initial induction phase) – to assess the efficacy of the drug in maintaining remission. It is planned to enroll 822 patients, and randomize them to active treatment or placebo (in 2:1 ratio).
The committee highlighted several critical points.
(A) On completion of the induction study, all the subjects who received icotrokinra will enter the maintenance study, and continue to receive this drug irrespective of whether they had a beneficial response to the study drug during the induction phase or not.
(B) During the presentation, the company presented a sample size calculation to show that the sample size needed for the induction study (assuming 11% response rate in the placebo group and a difference of 12% in the treated group) is much smaller (of the order of 250).
(C) It may not be justifiable to expose a nearly 3-fold larger number of subjects to this treatment and for a prolonged duration (of 52 weeks) – in particular those who do not improve following the induction therapy – especially when determination of safety is one of the objectives of the protocol.
As per the expert panel , the above points need to be justified, or the trial needs to be modified to include fewer patients. Also, only those with clinical response during the induction phase (and not those without clinical response) should be continued to the maintenance phase.
Accordingly, firm has been asked to submit a response for further review by the committee.
