CDSCO Requests Protocol Revisions for Novartis ITU512 Sickle Cell Disease Trial
Key Insights
India's drug regulatory authority has asked Novartis to revise its clinical trial protocol for ITU512, an investigational therapy targeting sickle cell disease (search) and β-thalassemia (search) through fetal hemoglobin (search) modulation.
The Subject Expert Committee raised concerns about endpoint definitions, requiring scientific justification for the >15% fetal hemoglobin (search) increase threshold and patient inclusion criteria.
Novartis must provide Phase I safety data and detailed sample size justification before the hemoglobin-targeting therapy can proceed to clinical testing in India.
India's Central Drugs Standard Control Organisation (CDSCO (search)) has requested significant protocol revisions from Novartis for its investigational therapy ITU512, designed to treat sickle cell disease (search) and β-thalassemia (search) by modulating fetal hemoglobin (search) levels.
The regulatory review took place during the 8th Subject Expert Committee (Haematology) meeting held on July 15, 2025, at CDSCO (search) headquarters in New Delhi. Novartis presented Protocol No.CITU512A12101, Version 01, dated July 29, 2024, for the advanced therapeutic candidate.
Primary Endpoint Concerns
The committee identified critical issues with the trial's primary endpoint definition, specifically regarding fetal hemoglobin (search) (HbF) measurements. According to the SEC, the primary endpoint must be clearly specified in terms of fetal hemoglobin increase greater than 15%, with this threshold requiring scientific justification based on prior studies, regulatory benchmarks, or clinical relevance.
The panel also requested justification for including patients with an absolute fetal hemoglobin (search) percentage below 15% in the study population. During the presentation, the SEC noted that definitions of both primary and secondary endpoints were not properly aligned with the submitted protocol.
Protocol Design Requirements
The committee emphasized that criteria for efficacy evaluation must be explicitly defined throughout the protocol. Additionally, exploratory endpoints such as vaso-occlusive crisis (VOC) events must be incorporated into the initial protocol design rather than being addressed separately.
The regulatory body also identified misalignment between the presented endpoint definitions and the submitted protocol documentation, requiring comprehensive revision to ensure consistency.
Safety Data and Dosing Justification
Novartis was directed to submit Phase I data, including safety and hemolysis profiles, from either the current study or any other country where ITU512 has undergone testing. The committee specifically requested detailed justification for both the proposed sample size and dosing regimen.
The therapeutic candidate ITU512 represents a potential advancement in treating hemoglobinopathies by targeting fetal hemoglobin (search) modulation, addressing conditions that affect millions of patients globally with sickle cell disease (search) and β-thalassemia (search).
"Accordingly, the firm shall submit the response for further review by committee," the SEC recommended, indicating that trial approval remains contingent on addressing these regulatory concerns.