Revise Itolizumab phase 3 study protocol for Covid-19: CDSCO panel tells Biocon

New Delhi: After reviewing Biocon's Phase III trial protocol for Itolizumab for treating Covid-19 patients, the Subject Expert Committee (SEC) functional under the Central Drug Standard Organization (CDSCO) has recommended the firm to revise the protocol and submit the revised study protocol for further assessment by the Committee.

This came after Biocon Limited presented the proposal of Phase III trial protocol no. BIO-ITOLIZ-304 Version: 1.0, dated July 21,2021.

Last year, the Medical Dialogues Team had reported that Biocon Ltd. had received the Drugs Controller General of India's (DCGI) approval to market Itolizumab (ALZUMAb®) Injection 25mg/5mL solution for emergency use in India for the treatment of cytokine release syndrome (CRS) in moderate to severe ARDS (acute respiratory distress syndrome) patients due to COVID-19.

The Indian drug regulatory agency had approved itolizumab for 'restricted emergency use' in moderate to severe acute respiratory distress syndrome (ARDS) owing to COVID-19 based on the data obtained from phase II, open-label, randomised, placebo-controlled trial conducted in 30 COVID-19 patients.

Despite the fact that the DCGI had approved Itolizumab for "restricted emergency use" in infected patients, the National Task Force on COVID-19 had excluded it from clinical management protocols for treating the disease.

Itolizumab was launched in India in 2013 under the brand name ALZUMAb. Itolizumab is Biocon's second 'lab to market' novel biologic after Nimotuzumab and offers a 'best-in-class' biologic drug for acute psoriasis.

Biocon repurposed Itolizumab, an anti-CD6 IgG1 monoclonal antibody for treating chronic plaque psoriasis, for the treatment of cytokine release syndrome (CRS) in moderate to severe acute respiratory distress syndrome (ARDS) patients due to COVID-19.

Itolizumab is a monoclonal antibody directed against CD6, a surface glycoprotein found on mature T cells, immature B cells, the B1a subset of B lymphocytes, and certain regions of the brain. By inhibiting CD6, itolizumab downregulates the synthesis of proinflammatory cytokines and adhesion molecules that eventually leads to reduced interferon-γ (IFNγ), interleukin (IL)-6, and tumour necrosis factor-α (TNFα) levels, along with reduced T-cell infiltration at the inflammatory sites. The potential utility of itolizumab in COVID-19, based on its unique mechanism of action in ameliorating cytokine release syndrome (CRS).

The SEC committee at its 178th meeting to examine COVID-19 related proposals under the accelerated approval process, held on 26.08.2021 and 27.08.2021 at CDSCO, thoroughly examined Biocon Limited's proposal for Phase III trial protocol no. BIO-ITOLIZ-304 Version: 1.0, dated July 21,2021.

After detailed deliberation, the committee recommended that the firm should revise the protocol with the following changes:

1) The "Adaptive" word should be removed from the proposed study protocol title.

2) Age group should be 18 to 65 years under the inclusion criteria.

3) For exclusion of TB subjects, three times TB gold (IGRA) test and one time TB PCR test with uniform lab method to be carried out.

4) Criteria for hospital discharge should be defined in the protocol.

5) There should be no re-dosing of the IMP, accordingly re-dosing of 0.8mg/kg should be removed from the proposed study protocol.

6) The interim analysis should be done once after 50% of total proposed subjects recruitment with 28days of treatment.

7) Clinical trial sites should be geographically distributed across the Country.

8) SoC should be uniform as per ICMR/GoI guideline at all participating sites and it should be recorded in CRF.

9) HRCT should be done for diagnosis of pulmonary fibrosis at screening/baseline and end of the treatment for the patients enrolled with chronic lung disease.

Furthermore, the committee directed the firm to submit a revised study protocol for further review by the committee.