A Phase I/II Dose Escalation/Adaptive Design Study to Evaluate the Safety and Efficacy of IMCY-0141 in Patients With Relapsing Remitting-Multiple Sclerosis (RR-MS)
Overview
- Phase
- Phase 1
- Status
- Active, not recruiting
- Sponsor
- Imcyse SA
- Enrollment
- 150
- Locations
- 1
- Primary Endpoint
- Ph I Primary safety endpoint (1) - Solicited injection site and systemic AEs
Overview
Brief Summary
The IMCY-MS-001 study is a study to test a new experimental drug, IMCY-0141, for the treatment of Relapsing-Remitting Multiple Sclerosis (RR-MS).
The pathophysiology of MS with known myelin autoantigens and T cell epitopes makes this disease a particularly attractive indication for development of an immunotherapeutic based on the Imcyse technology.
Based on the unique mechanism of action of the drug, IMCY-0141 administered as early as possible after confirmation of the diagnosis may potentially switch-off the autoimmune process and limit the corresponding myelin destruction. Newly (recently) diagnosed patients will be targeted to tackle the disease at its onset.
Before launching any efficacy studies, safety of IMCY-0141 in MS patients must be evaluated with a phase I, open-label, dose escalation clinical trial to evaluate the safety of three IMCY-0141 doses followed by a phase II, double-blind, randomized study with an adaptive design to determine if any IMCY-0141 dose(s) offer superior efficacy relative to placebo and to assess immune responses and biomarker data as potential early predictors of efficacy of IMCY-0141 in adults presenting with RR-MS.
Detailed Description
The Sample Size determined for this study is as follows:
Phase I:
A total of 12 patients (4 patients in each of 3 dose cohorts) are planned to be enrolled. The study sample size has been estimated as adequate to provide a reliable safety assessment of the tested doses. All primary, secondary and exploratory endpoints will be summarized by descriptive statistics (continuous variables) or frequency tables (categorical variables), by dose group and overall. Additional patients may be enrolled if requested by the IDMC (Independent Data Monitoring Committee).
Phase II:
The sample size estimation is based on the total cumulative number of CUAL observed on brain MRI scans from week 12 till week 36. The study sample size has been estimated as adequate to determine if any IMCY-0141 doses offer superior efficacy (as measured by CUAL) relative to placebo. Using the negative binomial model for CUAL, a maximum total of 150 patients are planned to be enrolled (including the 12 patients enrolled in phase I), with 30 patients randomized to each of five groups:
- Placebo
- IMCY-0141 dose 1
- IMCY-0141 dose 2
- IMCY-0141 dose 3
- DMF (open label)
During the adaptive design phase (Phase IIa), a minimum of 40 patients will be enrolled (with 8 patients randomized to each of five groups) and analyzed along with the 12 phase I patients as detailed here:
- Placebo: 8 patients
- IMCY-0141 dose 1: 8 patients + 4 phase I patients
- IMCY-0141 dose 2: 8 patients + 4 phase I patients
- IMCY-0141 dose 3: 8 patients + 4 phase I patients
- DMF (open label) : 8 patients
During the Phase IIb part, up to 98 additional patients will be enrolled in order to get up to 150 patients spread over the groups selected for Phase IIb, with a maximum 30 patients randomized to DMF. These sample sizes are sufficient to deliver Type I errors less than 5% in our chosen null scenarios, and unconditional powers greater than 75% and conditional powers greater than 90% in our two alternative scenarios.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description
This is a two-step study with a phase I, open-label, dose escalation clinical trial to evaluate the safety of three IMCY-0141 doses followed by a phase II, double-blind, randomized study with an adaptive design to determine if any IMCY-0141 doses offer superior efficacy relative to placebo.
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Cohort 1 - Phase I (IMCY-0141 Dose 1)
The first dose (Cohort 1) will consist of the administration of 150 μg of peptide (IMCY-0141) in two separate injections of 75 μg each (500μl each).
Intervention: IMCY-0141 (Drug)
Cohort 2 - Phase I (IMCY-0141 Dose 2)
The second dose (Cohort 2) will consist of the administration of 450 μg of peptide (IMCY-0141) in two separate injections of 225 μg each (500μl each).
Intervention: IMCY-0141 (Drug)
Cohort 3 - Phase I (IMCY-0141 Dose 3)
The third dose (Cohort 3) will consist of the administration of 1350 μg of peptide (IMCY-0141) in two separate injections of 675 μg each (500μL each).
Intervention: IMCY-0141 (Drug)
Group 1 - Phase II (IMCY-0141 Dose 1)
Administration of IMCY-0141, 150 μg combined with alum adjuvant.
Intervention: IMCY-0141 (Drug)
Group 2 - Phase II (IMCY-0141 Dose 2)
Administration of IMCY-0141, 450 μg combined with alum adjuvant.
Intervention: IMCY-0141 (Drug)
Group 3 - Phase II (IMCY-0141 Dose 3)
Administration of IMCY-0141, 1350 μg combined with alum adjuvant.
Intervention: IMCY-0141 (Drug)
Group 4 (Placebo Group) - Phase II
Administration of placebo combined with alum adjuvant.
Intervention: Placebo (Drug)
Group 5 (Active Control Group) - Phase II
Parallel, Open-Label, Active Control Group Oral administration of Dimethyl Fumarate (DMF) given according to its SmPC for the whole duration of the study.
Intervention: Dimethyl Fumarate (Drug)
Outcomes
Primary Outcomes
Ph I Primary safety endpoint (1) - Solicited injection site and systemic AEs
Time Frame: Up to 36 weeks
Occurrence, intensity and relationship of any solicited injection site and systemic adverse events (AEs) during a 7-day follow-up period (i.e., day of study product administration and 6 subsequent days) after each IMCY-0141 administration analysing local injection site and systemic adverse events, clinical and laboratory data.
Ph I Primary safety endpoint (2) - Unsolicited injection site and systemic AEs
Time Frame: Up to 36 weeks
Occurrence, intensity and relationship of any unsolicited injection site (local) and systemic AEs occurring throughout the study period.
Ph I Primary safety endpoint (3) - All SAEs
Time Frame: Up to 36 weeks
Occurrence and relationship of all serious adverse events (SAEs) occurring throughout the study period.
Ph I Primary safety endpoint (4) - Abnormalities on different parameters
Time Frame: Up to 36 weeks
Occurrence and relationship of any abnormality in physical examination, vital signs, 12-lead ECG, MRI, haematological and biochemical laboratory parameters.
Ph II Primary efficacy endpoint - Number of CUAL
Time Frame: Week 12 to Week 36
Total cumulative number of CUAL observed on brain MRI scans (centralized reading) from week 12 till week 36 vs placebo.
Secondary Outcomes
- Ph II Secondary endpoint (2) - Unsolicited injection site and systemic AEs(Up to 36 weeks)
- Ph II Secondary endpoint (3) - All SAEs(Up to 36 weeks)
- Ph II Secondary endpoint (4) - Abnormalities on different parameters(Up to 36 weeks)
- Ph I/II Secondary endpoint (1) - Relapse rate(At Week 36)
- Ph I/II Secondary endpoint (2) - Relapse-free rate(At Week 36)
- Ph I/II Secondary endpoint (3) - EDSS Score(At Week 36)
- Ph I/II Secondary endpoint (4) - Neurofilament light chains levels(Up to 36 weeks)
- Ph II Secondary endpoint (1) - Solicited injection site and systemic AEs(Up to 36 weeks)