Clinical trial NCT03272269: Study of IMCY-0098 in Patients With Recent Onset Type 1 Diabetes
Official title: A Phase I Placebo-controlled, Double-blind, Dose Escalation Clinical Trial to Evaluate the Safety and Immune Responses of Imcyse's IMCY-0098 in Patients With Recent Onset Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Type 1 Diabetes Mellitus
Keywords: Diabetes Mellitus type 1
Autoimmune disease
Immunotherapy
Diabetes treatment
Residual beta cell function
Adult patients
Lead sponsor: Imcyse SA
Sponsor class: INDUSTRY
First posted: 2017-09-05
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This clinical study will evaluate the safety of an innovative approach expected to be disease-modifying by stopping the auto-immune-mediated destruction of islet β-cells in the pancreas. Three doses of the investigational product will be tested in successive cohorts. Although safety is the first objective of this study, we will gather efficacy data and perform a set of immunological tests to further understand the mechanism of action of this new approach in young adults with recent onset type 1 diabetes.


Eligibility criteria: Inclusion Criteria:

1. Male or female 18 to 30 years of age
2. Initial diagnosis of Type 1 diabetes according to ADA/WHO criteria within the past 6 months
3. Insulin requirement, as determined by the investigator
4. Presence of at least one autoantibody (GAD65, IA-2, or ZnT8)
5. Fasting C-peptide at screening \>0.2 nmol/L and/or stimulated C-peptide ≥ 0,4 nmol/L.
6. HLADR3-positive and/or HLADR4-positive
7. Willingness to undergo the insulin treatment prescribed by the physician
8. Body mass index (BMI) between 17-28 kg/m2 at screening
9. Fully informed written consent obtained
10. Males with reproductive potential should use barrier method of contraception (condom) from screening up to 90 days after last treatment with investigational product.
11. Women of childbearing potential should use an highly effective contraception method from screening and for the whole duration of the study.

Exclusion Criteria:

1. Ongoing or planned pregnancy during the whole duration of the study or lactation
2. Presence of significant medical conditions in particular chronic liver condition, chronic hematological disease, renal dysfunction of grade 2 or more according to the World Health Organization (WHO) Toxicity Scale .
3. Has any current signs or symptoms of infection at entry or within 2 weeks of entry or has received intravenous antibiotics within 2 months prior to the first planned administration of the study product
4. Has received any live, attenuated vaccine within 3 months prior to the first planned administration of the study product (i.e. 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. History of, or current malignancy (except excised basal cell skin cancer)
6. Clinical evidence of a diabetes-related complication that could interfere with patient's participation/completion of study
7. Primary or secondary immune deficiency disorders
8. Human Immunodeficiency virus (HIV), chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
9. Presence at screening of abnormal laboratory values grade 2 or more according to the World Health Organization (WHO) Toxicity Scale
10. Anti-diabetic treatments other than insulin in the week prior to first study drug administration
11. Ongoing treatment with immunosuppressive agents or treatment within the past year with the exception of topical or intra nasal corticosteroids.
12. Treatment with immunotherapy within the past 3 months
13. Treatment with an investigational drug within the past 3 months
14. Patients with a known hypersensitivity to any component of the drug product should be excluded from the study
15. Patients under treatment with statins at the time of screening.

Primary outcomes:
measure: Incidence of all adverse events reported for subjects
timeFrame: up to 24 weeks
Secondary outcomes:
measure: Assessment of residual beta cell function and markers of metabolic control
timeFrame: up to 24 weeks
Other outcomes:
measure: Assessment of T lymphocyte immune response to IMCY-0098
timeFrame: up to 24 weeks
Locations:
city: Brussels
country: Belgium
facility: Hôpital Erasme
city: Brussels
country: Belgium
facility: UZ Brussel
city: Gent
country: Belgium
facility: UZ Gent
city: Copenhagen
country: Denmark
facility: Bispebjerg and Frederiksberg Hospital
city: Nantes
country: France
facility: CHU de Nantes, Hôpital Laennec
city: Dresden
country: Germany
facility: GWT-TUD GmbH
city: Klaipėda
country: Lithuania
facility: Klaipeda University Hospital
city: Vilnius
country: Lithuania
facility: University Hospital Santaros Klinikos
city: Göteborg
country: Sweden
facility: Clinical Trial Center, CTC
city: Stockholm
country: Sweden
facility: ProbarE Stockholm
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust
city: Cardiff
country: United Kingdom
facility: Cardiff University
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter NHS Trust
city: London
country: United Kingdom
facility: Guy's and St. Thomas NHS Trust
city: London
country: United Kingdom
facility: St. Bartholomew's Hospital (Barts Health NHS Trust)
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle University
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
Study officials:
affiliation: Imcyse SA
name: Pierre Vandepapelière, MD
role: STUDY_DIRECTOR
affiliation: Hôpital Cochin, Paris, France
name: Christian Boitard, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Carlier VA, VanderElst L, Janssens W, Jacquemin MG, Saint-Remy JM. Increased synapse formation obtained by T cell epitopes containing a CxxC motif in flanking residues convert CD4+ T cells into cytolytic effectors. PLoS One. 2012;7(10):e45366. doi: 10.1371/journal.pone.0045366. Epub 2012 Oct 9.
citation: Malek Abrahimians E, Carlier VA, Vander Elst L, Saint-Remy JM. MHC Class II-Restricted Epitopes Containing an Oxidoreductase Activity Prompt CD4(+) T Cells with Apoptosis-Inducing Properties. Front Immunol. 2015 Sep 2;6:449. doi: 10.3389/fimmu.2015.00449. eCollection 2015.
citation: Malek Abrahimians E, Vander Elst L, Carlier VA, Saint-Remy JM. Thioreductase-Containing Epitopes Inhibit the Development of Type 1 Diabetes in the NOD Mouse Model. Front Immunol. 2016 Mar 2;7:67. doi: 10.3389/fimmu.2016.00067. eCollection 2016.