Syneos Health Asked to Clarify Phase II Tacrolimus Trial Protocol by CDSCO Panel

New Delhi: Following a thorough review of the Phase II clinical study protocol for Tacrolimus (T1695), the Subject Expert Committee (SEC) functioning under the Central Drug Standard Control Organisation (CDSCO) has asked Syneos Health India to provide justifications and clarifications on several technical issues for further deliberation.

This came after the drug maker Syneos Health India presented phase II clinical study protocol no. LT1695-201 version no. 3.0 dated 15 May 2025.

Tacrolimus (anhydrous) is a macrolide lactam containing a 23-membered lactone ring, originally isolated from the fermentation broth of a Japanese soil sample that contained the bacteria Streptomyces tsukubaensis. It has a role as an immunosuppressive agent and a bacterial metabolite.

Tacrolimus is an immunosuppressive drug whose main use is after organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection. It is also used in a topical preparation in the treatment of severe atopic dermatitis, severe refractory uveitis after bone marrow transplants, and the skin condition vitiligo.

At the recent SEC meeting for Ophthalmology, the expert panel flagged multiple points requiring clarification in the study design.

After detailed deliberation, the committee opined that the firm shall submit justification for the following technical issue raised by the SEC member for further deliberation and review.

1. The treatment for the nonresponders must be taken care of by the Sponsors.

2. The quantification of the grading of staining must be mentioned elaborately.

3. In cases of concomitant moderate to severe dry eyes, what will be the strategy and modifications in the study protocol.

4. The blood levels in ng/ml of these drugs will be measured by which specific equipment at all the study multicenters.

5. What will be the strategy of various examinations among the uncooperative children?

6. Artificial tears permitted during the washout period may be specified.

7. During the washout period, in-person safety assessment visits and additional telephonic safety assessment calls should be scheduled in the study design.

8. The term 'Investigator masked' follow-up should be rephrased for clarity.

9. The assessment for non-responder patients and the need for standard of care should not only be at visit 6 but specified from randomization till the end of the study.

10. Presence of Shield's ulcer should be added in the exclusion criteria.

11. The term 'corticosteroid responders' in the inclusion criteria needs to be defined.