FrexalimAB in Preservation of Endogenous insULIN Secretion Compared to Placebo in adUlts and Adolescents on Top of inSulin Therapy (FABULINUS)

Launched by SANOFI · Oct 31, 2023

Keywords

ClinConnect Summary

The FABULINUS trial is studying a new treatment called frexalimab for people with Type 1 Diabetes Mellitus (T1D) who are already using insulin. The goal of the trial is to see if frexalimab can help protect the body's ability to produce insulin. This study will last up to 135 weeks and includes a main treatment period of 52 weeks followed by an additional 52 weeks for safety monitoring. Participants will be randomly assigned to receive either frexalimab or a placebo (an inactive substance) without knowing which treatment they are receiving.

To be eligible for the trial, participants must be diagnosed with T1D and have started insulin therapy within the last 90 days. They should also have certain antibodies related to T1D and be vaccinated according to local guidelines. The trial is open to individuals aged 4 to 127, and both males and females can participate. Throughout the study, participants can expect regular check-ups and assessments to monitor their health and the effectiveness of the treatment. It’s important to note that there are specific health conditions and treatments that may exclude someone from participating, which will be assessed during the screening process.

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Eligibility criteria

• 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 visit.
• • 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, acquired or inherited bone/skeletal disorders including repeated bone fractures for unknown reason, juvenile osteoporosis, osteogenesis imperfecta, osteochondropathies, 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 drugs that may be used for treatment of T1D and type 2 diabetes other than insulin including but not limited to metformin, 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.