ABSTRACT: Interventions: The study will consist of 3 dosing cohorts. In each cohort, 3 participants will be treated with once weekly subcutaneous injections of INB03 at a dose of 0.3 (no more than 30 mg), 1.0 (no more than 100 mg) or 3.0 mg/kg (no more than 220 mg or 2 vials of INB03), respectively. INB03 will be administered weekly for 9 months or until disease progression as determined by the PI and/or participant intolerance as determined by the Principal Investigator (PI). However, participants may continue INB03 therapy at any time, including after study end at Month 9, on a compassionate use basis if the attending physician believes the subject is benefiting from the therapy in any way.
INB03 will be administered by a study nurse at clinical investigation site from Day 1 till Day 85 visits. At the discretion of the investigator patients may be allowed to self-administer INB03 at home from Month 4 visit onwards. Subjects who undergo home-administration of INB03 will be asked to bring all used, partially used, or unused contains to study staff at each study visit for completion of drug accountability and monitor adherence.
All subjects will receive their assigned INB03 dose through Month 3. After all subjects have
completed 3 months of therapy, an interim analysis will be conducted and an optimal dose for the Phase 2 trial will be determined by the Data Safety Monitoring Board (DSMB). Further dosing of INB03 after Month 3 may be adjusted to the selected dosage for Phase 2.
Primary outcome(s): Safety and tolerability of INB03 given by sub-cutaneous injection once a week. This outcome is incidence of grade 3 or greater AEs and SAEs as graded by NCI CTCAE criteria v 5.0. [Day 1, 3, 5, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78 & 85];Evaluate the pharmacokinetics (PK) of single dose and multiple doses of INB03. Due to the cross-reactivity of INB03 and serum soluble TNF in assay systems, the FDA recommended the Sponsor use serum soluble TNF levels as a measure of drug level during the clinical trials. An abbreviated PK study format will be used.[Four time points will be studied for the first dose PK and trough levels will be monitored for the multi-dose PK. Specifically measurements of human TNF-Alpha levels will be tested in blood samples collected at time 0, 1, 4 and 8 hours after the first INB03 dosing on Day 1. Trough levels will continue to be collected on Day 3 and prior to successive doses on Day 8, 15, 22, 29, 43, 57, 85, and Month 4-9.];The study will examine the following efficacy parameters throughout the study:
- change in hsCRP serum levels[Screening, Days 1, 8, 29, 43, 57, 71, 85, Months 4, 5, 6, 7, 8 and 9]
Study Design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Type of endpoint: Safety
