Overview

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

Status:
Recruiting
Trial end date:
2028-10-27
Target enrollment:
0
Participant gender:
All
Summary
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.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Sanofi
Treatments:
Insulin
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.

- 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.