FrexalimAB in preservation of endogenous insULIN secretion compared to placebo in adUlts and adolescents on top of inSulin therapy (FABULINUS).

Phase 1

Recruiting

Conditions: Type 1 diabetes mellitus
MedDRA version: 21.1Level: PTClassification code: 10067584Term: Type 1 diabetes mellitus Class: 100000004861
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: CTIS2022-500531-36-00

Lead Sponsor: Sanofi-Aventis Recherche & Developpement

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: All

Target Recruitment: 240

Inclusion Criteria

Participants who meet the criteria of T1D according to American Diabetes Association, Initiated exogenous insulin replacement therapy not longer than 90 days prior to screening visit at which random C-peptide will be assessed (V1)., Receiving at least one of the following T1D standard of care (SOC), insulin hormone replacement therapy oone or multiple daily injections (MDI) of basal insulin, prandial insulin and/or premixed insulin, or ocontinuous subcutaneous insulin infusion (CSII), Participants must be positive for at least 1 of the following T1D autoantibodies confirmed by medical history and/or obtained at study screening: oGlutamic acid decarboxylase (GAD-65) oInsulinoma Antigen-2 (IA-2) oZinc-transporter 8 (ZnT8) or oInsulin (if obtained not later than 10 days after exogenous insulin therapy initiation), Have random C-peptide levels = 0.2 nmol/L determined at screening, Be vaccinated according to the local vaccination schedule. Any vaccinations should take place at least 28 days prior to randomization for non-live vaccines and at least 3 months prior to randomization for live vaccines, Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

Exclusion Criteria

Serious systemic viral, bacterial or fungal infection (eg, pneumonia, pyelonephritis), infection requiring hospitalization or IV antibiotics or significant chronic viral (including history of recurrent or active herpes zoster, acute or active cytomegalovirus (CMV), Epstein-Barr Virus (EBV) as determined at screening), bacterial, or fungal infection (eg, osteomyelitis) 30 days before and during screening., History of malignancy of any organ system, treated or untreated, within 5 years of screening, regardless of whether there is evidence of local recurrence or metastases, Systemic corticosteroids (duration >7 days), adrenocorticotropic hormone 1 month prior to screening., Any IV, IM or SC administered biologic treatments, < 3 months or < than 5 half-lives (whichever is longer), prior to randomization., Any live (attenuated or viral-vector) vaccine (including but not limited to varicella zoster, oral polio, nasal influenza, rabies) within 3 months prior to randomization., Any non-live (inactivated, mRNA, recombinant, conjugate, toxoid) vaccine administered less than 28 days prior to randomization., Other medications not compatible or interfering with IMP at discretion of investigator., Any immunosuppressive therapy within 12 weeks prior to randomization, Course of Thymoglobulin®, teplizumab or other immunomodulatory treatments at any time., Any glucagon-like peptide 1 (GLP-1) agonists and sodium–glucose cotransporter- 2 and 1 (SGLT2/1) inhibitor and verapamil within 2 weeks prior to screening., Abnormal laboratory test(s) at screening., Participants with a history of invasive opportunistic infections, such as, but not limited to histoplasmosis, listeriosis, coccidioidomycosis, candidiasis, pneumocystis jirovecii, and aspergillosis, regardless of resolution., Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest X-rays (posterior anterior and lateral), and/or TB testing. Blood testing (eg, QuantiFERON® TB Gold test) is strongly preferred; if not available, any local approved TB test is allowed., Evidence of any clinically significant, severe or unstable, acute or chronically progressive, uncontrolled infection, medical or surgical condition (eg, but not limited to, cerebral, cardiac, pulmonary, renal, hepatic, gastrointestinal, neurologic, or any known immune deficiency), or any condition that may affect participant safety in the judgment of the Investigator (including vaccinations which are not updated based on local regulation)., History or current hypogammaglobulinemia., History of a systemic hypersensitivity reaction or significant allergies, other than localized injection site reaction, to any humanized mAb. Clinically significant multiple or severe drug allergies, intolerance to topical corticosteroids, or severe post-treatment hypersensitivity reactions (including, but not limited to, erythema multiforme major, linear IgA dermatosis, toxic epidermal necrolysis, and exfoliative dermatitis)., Has other autoimmune diseases (eg, rheumatoid arthritis [RA], polyarticular juvenile idiopathic arthritis [pJIA], psoriatic arthritis [PsA], ankylosing spondylitis [AS], MS, SLE), except autoimmune thyroiditis with controlled function of thyroid gland and celiac disease (at discretion of investigator)., History, clinical evidence, suspicion or significant risk for thromboembolic events, as well as myocardial infarction, stroke, antiphospholipid syndrome, other prothrombotic disorders and/or partici

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate the efficacy of different doses of frexalimab in comparison with placebo and in addition to standard of care (SOC) on endogenous insulin secretion in participants (12-21 y.o.) with newly diagnosed T1D over a 52-week period.;Secondary Objective: To evaluate the efficacy of frexalimab in comparison to placebo and on top of SOC on glycemic control and endogenous insulin secretion in participants (12-21 y.o.) with newly diagnosed T1D, To evaluate the safety and tolerability of frexalimab versus placebo in all participants, To characterize pharmacokinetics (PK) of frexalimab in all participants, To evaluate the potential for immunogenicity of frexalimab in all participants, To assess the impact of frexalimab treatment on caregiver- and/or patient-reported clinical outcome measurements in all participants;Primary end point(s): Change from baseline to W52 in mean 2h mixed meal tolerance test (MMTT) stimulated C-peptide concentration

Secondary Outcome Measures