E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067584 |
E.1.2 | Term | Type 1 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To determine the change in stimulated C-peptide response during the first two hours of a mixed meal tolerance test (MMTT) from baseline to 48 weeks for two doses of IMCY-0098 versus placebo. |
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E.2.2 | Secondary objectives of the trial |
(1) To determine the changes in stimulated C-peptide response during the first two hours of a mixed MMTT from baseline to 12 and 24 weeks and to month 18 and month 24. (2) To determine the difference in Dried Blood Spots (DBS) fasted C-peptide between treatment and placebo groups from baseline to 48 weeks. (3) To determine the changes in DBS C-peptide measurements until visit 11 comparing each dose with placebo. (4) To determine the effects of each dose of IMCY-0098 on HbA1c, hypoglycaemic events, Diabetes Ketoacidosis episodes, daily total insulin dose and CGM measures. (5)To evaluate the impact of IMCY-0098 at each dose on autoantibodies against GAD65, IA 2, ZnT8 and insulin over time. (6)To evaluate the safety features of IMCY-0098. (7)To evaluate the correlation between the immune changes induced by IMCY-0098 and the C-peptide evolution measured as the area under the stimulated C-peptide response curve over the first two hours of a MMTT at baseline and all timepoints.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Mechanistic sub-study for HLA DR4 negative /HLA DR3 positive participants: sub-study added in v3.0 (dated 26 Mar 2021) of the main study protocol. Up to 24 HLA DR4-/HLA DR3+ participants will be included in this mechanistic sub-study. The goal is to evaluate, characterize and compare the immune reaction of HLA DR4-/HLA DR3+ participants with the immune reaction of the HLA DR4+/HLA DR3+ participants included in the main study. The immune data acquired in this sub-population will be very informative to support decisions in terms of participant population for future clinical trials on adults but also on adolescents and children. Safety data will be collected and will contribute to the overall safety database for IMCY-0098. |
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E.3 | Principal inclusion criteria |
(1) Have given written informed consent. (2) Participants aged ≥18 years and < 45 years at the time of consent. (3) Must have a diagnosis of T1D within maximum 9 weeks duration at screening (date of the first insulin injection). (4) Must have at least one or more diabetes-related autoantibodies present at screening (GAD65, IA-2, or ZnT8). (5) Must have random C-peptide levels ≥200 pmol/L measured at screening. (6) Must be HLA DR4 positive for the main study. a. Up to 24 participants with an HLA DR4 negative status but HLA DR3 positive will be eligible for the sub-study. (7) Must be willing to comply with intensive diabetes management. (8) Be treated with insulin therapy in accordance with local standard of care. (9) 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 - True abstinence (where this is in accordance with the participants preferred and usual lifestyle) (10) All females must have a negative serum pregnancy test at screening. Women sexually active and of childbearing potential must agree to use a highly effective contraception method from screening up to 90 days after last treatment with the investigational product. |
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E.4 | Principal exclusion criteria |
(1) Clinically significant abnormal full blood count (FBC), renal function or liver function at screening, including a.Be immunodeficient or have clinically significant chronic lymphopenia: Leukopenia (< 3,000 leukocytes /µL), neutropenia (<1,500 neutrophils/µL), lymphopenia (<800 lymphocytes/µL), or thrombocytopenia (<100,000 platelets/µL). b.Evidence of renal dysfunction with creatinine greater than 1.5 times the upper limit of normal. c.Evidence of liver dysfunction with aspartate aminotransferase (AST) or alanine transaminase (ALT) greater than 3 times the upper limits of normal. 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. (2) Have signs or symptoms of serious active infection requiring IV antibiotics and/or hospitalization at study entry. (3) Have signs or symptoms of active COVID infection or a positive COVID PCR test during the screening period. (4) Has received any live, attenuated vaccine within 3 months prior to the first planned administration of the study product (which includes, but 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). (5) Be currently pregnant or lactating, or anticipate getting pregnant until at least 24 weeks after last study drug administration. (6) Require the use of immunosuppressive agents including chronic use of systemic steroids. Topical, inhalational or intranasal corticosteroids are allowed. (7) Have evidence of current or past human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection. (8) Presence of any uncontrolled disease (including uncontrolled autoimmune disease) or abnormal clinical laboratory results that may interfere with study conduct as judged by the investigator. (9) History of, or current malignancy (except excised basal cell skin cancer). (10) Current or ongoing use of non-insulin pharmaceuticals that affect glycaemic control within the 7 days prior to screening visit. (11) Active participation in another T1D treatment study or any investigational intervention study in the previous 30 days. (12) Known hypersensitivity to any component of the drug product. (13) CRO or Sponsor employees or employees under the direct supervision of the Investigator and/or involved directly in the study. (14) Be diagnosed with Latent Autoimmune Diabetes in Adults (LADA) |
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E.5 End points |
E.5.1 | Primary end point(s) |
The area under the stimulated C-peptide response curve over the first two hours of a mixed meal tolerance test (MMTT) at baseline and 48 weeks in the IMCY-0098 groups compared to placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
(1) The area under the stimulated C-peptide response curve over the first two hours of a mixed meal tolerance test (MMTT) at baseline, at 12 and 24 week and at month 18 and month 24 in the IMCY-0098 groups compared to placebo (2) The DBS C-peptide measurements from baseline to 48 weeks (3) The DBS C-peptide responses at each visit until visit 11 (4) 4.1.Change in HbA1c, from baseline to 24 and 48 weeks and to 18 and 24 months 4.2.Number of treatment-emergent severe hypoglycaemic episodes. Severe hypoglycaemia denotes severe cognitive impairment requiring external assistance for recovery according to the American Diabetes Association (ADA) 4.3.Number of treatment-emergent episodes of diabetic ketoacidosis (DKA) 4.4.Change in insulin requirements, baseline to 24 and 48 weeks and to 18 and 24 months as the daily total dose (three days average) in units per kg body weight (BW) 4.5.Continuous glucose monitoring (CGM) time in range (70-180 mg/dL, 3.9-10.0 mmol/L), time above range (>180 mg/dL, >10.0 mmol/L), time below range (<70 mg/dL, < 3.9 mmol/L) during 10 days at 12, 24 and 48 weeks and to 18 and 24 months compared to the reference period (first 10 days after randomization) (5) Change in T1D associated autoantibodies (GADA, IAA, IA-2A and ZnT8A) from baseline to 24 and 48 weeks and to 18 and 24 months (6) 6.1 Occurrence, intensity and relationship of any listed injection site and systemic AEs during a 7-day follow-up period (i.e., day of study product administration and 6 subsequent days) after each IMCY-0098 or placebo dose 6.2 Occurrence, intensity and relationship of any unlisted injection site and AEs throughout the study period 6.3 Occurrence and relationship of all SAEs throughout the study period 6.4 Occurrence and relationship of any abnormality in physical examination, vital signs, 12-lead ECG 6.5 Measure of CD4+/CD8+ lymphocytes ratio (7) 7.1 The area under the stimulated C-peptide response curve over the first two hours of a mixed meal tolerance test (MMTT) at baseline, 12, 24 and 48 weeks and at month 18 and month 24 in the IMCY-0098 groups compared to placebo. 7.2 Changes in the proinsulin epitope C20-A1-specific CD4+T lymphocyte responses longitudinally based on gene expression following treatment with IMCY-0098 and versus placebo. 7.3 Changes in CD4+ and CD8+ T cell responses specific for proinsulin, GAD65 and IGRP longitudinally based on gene expression following treatment with IMCY-0098 and versus placebo |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
(1)MMTT: D0, w12, w24, w48, M18, M24 (2)The DBS C-peptide: at each visit (3)- HbA1c: D0, w12, w24, w48, M18, M24 -# of treatment-emergent severe hypoglycaemic episodes /# of treatment-emergent episodes of DKA: throughout the study period -Change in insulin requirements: D0, w24, w48, M18, M24 -CGM: D0, w12, w24, w48, M18, M24 (4) GADA, IAA, IA-2A and ZnT8A: D0, w24, w48, M18, M24 (5)- any listed AEs: after administration (7days) -AEs / SAEs: throughout the study period -Physical examination: screening, (D0), w6, w12, w24, w48, M18, M24 -vital signs: each visit -12-lead ECG: screening, w12, w48, M24 -CD4+/CD8+ lymphocytes ratio: at each visit (6) - area under the stimulated C-peptide response curve at D0, w12, w24, w48, M18 and M24 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 8 |