FrexalimAB in Preservation of Endogenous insULIN Secretion Compared to Placebo in adUlts and Adolescents on Top of inSulin Therapy (FABULINUS)
Research Study on Investigational Medication for Type 1 Diabetes

Study Overview
This is a randomized, parallel group, double-blind Phase 2 study that consists of 2 parts. In Part A the safety of the highest dose-level of frexalimab in adults (age range 18-35 y.o.) will be established. In Part B, a dose-finding study (adolescents and young adults, 12-21 y.o.) evaluating the safety and efficacy of 3 age-adjusted dose-levels of frexalimab in comparison with placebo in participants with newly diagnosed T1D on insulin treatment. The purpose of this study is to determine safety and efficacy of different dose-levels of frexalimab, by assessment of preservation of endogenous insulin secretion in participants with newly diagnosed T1D aged 12 to 21 years compared with placebo on top of standard insulin therapy, and to determine the dose-response relationship and minimal efficacious dose in Part B. Study details include: - Screening period: at least 3 weeks and up to 5 weeks (Up to 11 days may be required to get investigational medicinal product [IMP] on site. Enrollment date of the participant must take into consideration this constraint.) - Double-blind treatment period (104 weeks): -- Main treatment period: 52 weeks -- Blinded extension: 52 weeks - Safety follow-up: 26 weeks (not applicable for participants entering the open-label study) The treatment duration will be up to 104 weeks, the total study duration will be up to 135 weeks.
Eligibility Criteria
You may be eligible for this study if you meet the following criteria:
- Conditions: Type 1 Diabetes Mellitus
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Age: 12 years - 35 years
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Gender: All
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
- one or multiple daily injections (MDI) of basal insulin, prandial insulin and/or premixed insulin, or
- continuous 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:
- Glutamic acid decarboxylase (GAD-65)
- Insulinoma Antigen-2 (IA-2)
- Zinc-transporter 8 (ZnT8) or
- Insulin (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.
- 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 participants requiring antithrombotic treatment.
- Diabetes of forms other than autoimmune T1D that include but is not limited to genetic forms of diabetes, maturity-onset diabetes of the young (MODY), latent autoimmune diabetes of the adult (LADA), secondary to medications or surgery, type 2 diabetes by judgement of the investigator.
- 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 co-transporter-2 and 1 (SGLT2/1) inhibitor and verapamil within 2 weeks prior to screening.
- Abnormal laboratory test(s) at screening.
The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
This study investigates the safety and efficacy of different doses of an investigational medication in people with newly diagnosed Type 1 Diabetes (T1D). Type 1 diabetes is a chronic disease where the body's defense system mistakenly attacks specific cells within the pancreas, which make insulin. Insulin helps control sugar in the blood. When these cells are damaged, they cannot make enough insulin. This means people with Type 1 diabetes need to take insulin every day to keep their blood sugar at safe levels. The study includes two parts: Part A focuses on adults aged 18-35 years to establish the safety of the highest dose, while Part B involves adolescents and young adults aged 12-21 years to find the best dose compared to a placebo.
Participants will undergo a screening period lasting between 3 to 5 weeks. Following this, there is a double-blind treatment period of 104 weeks, which includes a main treatment period of 52 weeks and a blinded extension of another 52 weeks. There is also a safety follow-up period lasting 26 weeks for those not entering an open-label study. A placebo is an inactive substance that looks like the investigational medicine but does not contain any medicine.
- Who can participate: Participants aged 12 to 21 years with newly diagnosed Type 1 Diabetes who have started insulin therapy within the last 90 days are eligible. They must use contraception, test positive for specific T1D autoantibodies, and have certain levels of C-peptide. Exclusion criteria include active infections and other specified conditions. Vaccination according to local schedules is also required.
- Study details: Participants will receive either the investigational medication or a placebo, in addition to their standard insulin therapy. A placebo is an inactive substance that looks like the investigational medicine but does not contain any medicine. The study aims to assess how well the investigational medication helps preserve the body's ability to produce insulin naturally.
- Study Timelines: The study will last up to 135 weeks.