A Phase IIa, Randomized, Double-blind, Dose Comparison, Placebo-controlled, Multi-centre Clinical Trial to Evaluate the Immune Signature of the Treatment With the Imotope IMCY-0098 and Its Effect on the Preservation of Beta-cell Function in Adult Patients With a Recent Onset Type 1 Diabetes
Overview
- Phase
- Phase 2
- Status
- Terminated
- Sponsor
- Imcyse SA
- Enrollment
- 110
- Locations
- 29
- Primary Endpoint
- Change in stimulated C-peptide response during the first two hours of a mixed meal tolerance test (MMTT) from baseline to 48 weeks between IMCY-0098 and placebo groups
Overview
Brief Summary
The IMPACT study is a study to test a new experimental drug, IMCY-0098, for the treatment of type 1 diabetes (T1D).
In most people with type 1 diabetes, the pancreas loses its ability to make insulin because some cells of the body's own immune system mistakenly attack and destroy the cells in the pancreas that produce insulin (islet beta-cells).
The study drug IMCY-0098 is being developed to stop the body's own immune system attacking and destroying the insulin-producing cells. When injected, it will induce new immune cells that will specifically destroy the bad immune cells responsible for the damage to the pancreas.
IMCY-0098 has previously been tested on recently diagnosed type 1 diabetes patients in the first clinical study between 2017 and 2019 to collect information on the safety of IMCY-0098. The next step is to test the best dose and the best number of injections that show the drug can give a benefit. Two doses of IMCY-0098 will be tested and they will be compared to a placebo. Safety information will also be collected during the study for all the participants.
Detailed Description
The main study will include 84 HLA DR4+ patients. In addition, up to 24 HLA DR4-/DR3+ patients will be included in a mechanistic substudy.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 44 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Have given written informed consent.
- •Participants aged ≥ 18 years and \< 45 years at the time of consent
- •Have a diagnosis of T1D within maximum 9 weeks at screening (date of the first insulin injection)
- •Must have at least one or more diabetes-related autoantibodies present at screening (GAD65, IA-2, or ZnT8)
- •Must have random C-peptide levels ≥ 200 pmol/L measured at screening
- •Must be Human Leukocyte Antigen (HLA) DR4 positive to participate in the main study OR HLA DR4 negative but HLA DR3 positive to participate in the substudy
- •Be willing to comply with intensive diabetes management
- •Be treated with insulin therapy in accordance with the local standard of care
- •Males with reproductive potential must agree to use adequate contraception up to 90 days after the completion of the last treatment. This includes:
- •Barrier contraception (condom and spermicide) or
Exclusion Criteria
- •Clinically significant abnormal full blood count (FBC), renal function or liver function at screening including
- •Be immunodeficient or have any clinically significant chronic lymphopenia: Leukopenia (\< 3,000 leukocytes /μL), neutropenia (\<1,500 neutrophils/μL), lymphopenia (\<800 lymphocytes/μL), or thrombocytopenia (\<100,000 platelets/μL)
- •Evidence of renal dysfunction with serum creatinine greater than 1.5 times the upper limit of normal OR (US ONLY) estimated Glomerular Filtration Rate (eGFR) calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) \<90 mL/min per 1.73 m2 in absence of other signs of CKD or rapidly progressing renal disease
- •Evidence of liver dysfunction with aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 3 times the upper limits of normal or (US ONLY) total bilirubin ≥ 2x Upper Limit of Normal (ULN) or Alkaline phosphatase ≥ 2x ULN. For participants presenting with values above ULN but below above threshold for these parameters, the underlying reason should be investigated by the site team to exclude liver disease. Patients for which a liver disease would be diagnosed will be excluded from the study.
- •Participants with elevated unconjugated bilirubin (Gilbert's syndrome) are eligible if bilirubin is ≤ 3 times the upper limits of normal and hepatic enzymes and function are otherwise normal (AST/ALT/Alkaline phosphatase within ULN), and there is no evidence of hemolysis
- •Have signs or symptoms of serious active infection requiring IV antibiotics and/or hospitalization at study entry
- •Have signs or symptoms of active COVID infection or a positive COVID PCR test during the screening period
- •Have received any live attenuated vaccine within 3 months prior to the first planned administration of the study product (which includes, but is not limited to: oral poliomyelitis vaccine, measles-mumps-rubella vaccine, yellow fever vaccine, Japanese encephalitis vaccine, dengue vaccine, rotavirus vaccine, varicella vaccine, live-attenuated zoster vaccine, Bacillus Calmette-Guérin \[BCG\] vaccine, oral typhoid vaccine)
- •Be currently pregnant or lactating, or anticipate getting pregnant until at least 24 weeks after last study drug administration
- •Require the use of immunosuppressive agents including chronic use of systemic steroids. Topical, inhalational or intranasal corticosteroids are allowed
Arms & Interventions
IMCY-0098, low dose
The dose A (Cohort 1) will consist of subcutaneous administrations of 450 µg of the peptide in two separate injections of 225 µg each (500 µL each).
Intervention: IMCY-0098 450 μg (Drug)
IMCY-0098, high dose
The dose B (Cohort 2) will consist of subcutaneous administrations of 1350 µg of the peptide in two separate injections of 675 µg each (500 µL each).
Intervention: IMCY-0098 1350 μg (Drug)
Placebo
Participants randomized to placebo will receive subcutaneous administrations of identical volumes of placebo solution to maintain study blind.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Change in stimulated C-peptide response during the first two hours of a mixed meal tolerance test (MMTT) from baseline to 48 weeks between IMCY-0098 and placebo groups
Time Frame: From baseline to 48 weeks
The area under the stimulated C-peptide response curve over the first two hours of a MMTT
Secondary Outcomes
- Changes in stimulated C-peptide response during the first two hours of a MMTT for the two doses of IMCY-0098 versus placebo(From baseline to 24 months)
- Difference in Dried Blood Spots (DBS) fasted C-peptide between treatment and placebo groups(From baseline to 48 weeks)
- Effects of each dose of IMCY-0098 on hypoglycaemic events(From baseline to 24 months)
- Effects of each dose of IMCY-0098 on daily total insulin dose(From baseline to 24 months)
- To evaluate the safety features of IMCY-0098 during treatment period(Up to 7 days after the last dose)
- To evaluate the safety features of IMCY-0098 during the whole study duration(Up to 48 weeks)
- To evaluate the safety features of IMCY-0098 on lymphocytes ratio(Up to 48 weeks)
- Changes in DBS C-peptide measurements at each visit comparing each dose with placebo(From baseline to 24 months)
- Effects of each dose of IMCY-0098 on Continuous Glucose Monitoring (CGM) measures(From baseline to 24 months)
- Effects of each dose of IMCY-0098 on HbA1c(From baseline to 24 months)
- Effects of each dose of IMCY-0098 on diabetic ketoacidosis (DKA) episodes(From baseline to 24 months)
- Impact of IMCY-0098 at each dose on autoantibodies against GAD65, IA 2, ZnT8 and insulin over time(From baseline to 24 months)