FrexalimAB in Preservation of Endogenous insULIN Secretion Compared to Placebo in adUlts and Adolescents on Top of inSulin Therapy (FABULINUS)
- Conditions
- Type 1 Diabetes Mellitus
- Interventions
- Registration Number
- NCT06111586
- Lead Sponsor
- Sanofi
- Brief Summary
This is a randomized, parallel group, double-blind Phase 2 study with a 52-week blinded extension evaluating the safety and efficacy of 3 dose levels of frexalimab in comparison with placebo in participants with newly diagnosed T1D on insulin treatment.
Study details include:
Screening period: at least 3 weeks and up to 5 weeks
Double-blind treatment period (104 weeks):
* Main treatment period: 52 weeks
* Blinded extension: 52 weeks Safety follow-up: up to 26 weeks The treatment duration will be up to 104 weeks, the total study duration will be up to 135 weeks.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 192
-
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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Frexalimab Dose 1 Frexalimab - Frexalimab Dose 2 Frexalimab - Frexalimab Dose 2 Insulin - Frexalimab Dose 3 Frexalimab - Frexalimab Dose 3 Insulin - Placebo Placebo Matching Placebo Placebo Insulin Matching Placebo Frexalimab Dose 1 Insulin -
- Primary Outcome Measures
Name Time Method Change from baseline to W52 in mean 2h mixed meal tolerance test (MMTT) stimulated C-peptide concentration Baseline to Week 52 mixed meal tolerance test (MMTT) stimulated C-peptide concentration is to be calculated from AUC
- Secondary Outcome Measures
Name Time Method Time in range (70-180 mg/dL), assessed by CGM at W52 and W104 At Week 52 and Week 104 Proportion of participants who remain C-peptide positive (mean 2h MMTT stimulated C-peptide concentration ≥0.2 nmol/L) at W52 and W104 At Week 52 and Week 104 mixed meal tolerance test (MMTT) stimulated C-peptide concentration is to be calculated from AUC
Proportion of participants with reduction from baseline to W52 and W104 of less than 10% in mean 2h MMTT stimulated C-peptide concentration From baseline to Week 52 and Week 104 mixed meal tolerance test (MMTT) stimulated C-peptide concentration is to be calculated from AUC
Proportion of participants with partial remission at W52 and W104 (defined as IDAA1c score ≤9.0, where it is calculated as HbA1c [%] + 4x insulin dose [IU/kg/day]) At Week 52 and Week 104 Change from baseline to W52 and W104 in insulin dose [IU/kg/day] From baseline to Week 52 and Week 104 HbA1c level and its change from baseline at W52 and W104 From baseline to Week 52 and Week 104 Proportion of participants with HbA1c ≤6.5% and requiring no injections of exogenous insulin at W52 and W104 At Week 52 and Week 104 Proportion of participants with HbA1c ≤6.5% and requiring ≤0.25 IU of insulin at W52 and W104 At Week 52 and Week 104 Proportion of participants with HbA1c <7% at W52 and W104 At Week 52 and Week 104 Incidence of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs) and TEAEs leading to treatment discontinuation Until Week 130 Number of participants with at least one hypoglycemic event Until Week 130 Number of participants with at least one hyperglycemic episode Until Week 130 Number of participants with at least one diabetic ketoacidosis (DKA) event Until Week 130 Number of participants with clinically significant changes in vital signs, electrocardiogram (ECG), and/or laboratory evaluation Until Week 130 Height and growth rate over time (for participants <18 y.o. at screening) Until Week 130 Frexalimab plasma concentrations over time Until Week 104 Change from baseline to W52 and W104 in Pediatric Quality of Life (PedsQL) Diabetes Management domain score (all participants) From baseline to Week 52 and Week 104 Incidence of anti-drug antibodies (ADAs) over time Until Week 130 Change from baseline to W52 and W104 in PedsQL Diabetes Symptoms domain score (all participants) From baseline to Week 52 and Week 104 Change from baseline to W52 and W104 in Problem Areas In Diabetes (PAID) total score (all participants) From baseline to Week 52 and Week 104 Change from baseline to W52 and W104 in Diabetes Treatment Satisfaction Questionnaires (DTSQs) total and item scores (all participants) From baseline to Week 52 and Week 104 Change from baseline to W52 and W104 in PAID immediate and theoretical domain scores (caregivers of all participants 12-17 y.o.) From baseline to Week 52 and Week 104 Change from baseline to W52 and W104 in DTSQs Total and item scores (caregivers of all participants 12-17 y.o.) From baseline to Week 52 and Week 104 Time in tight range (TITR, 70 - 140 mg/dL), assessed by CGM at W52 and W104 Time in tight range (TITR, 70 - 140 mg/dL), assessed by CGM at W52 and W104 Change from baseline to W52 in IDAA1c score From baseline to Week 52 Change from baseline to W104 in mean 2h mixed meal tolerance test (MMTT) stimulated C-peptide concentration, calculated from AUC From baseline to Week 104
Trial Locations
- Locations (60)
Investigational Site Number : 3480002
🇭🇺Nyíregyháza, Hungary
Investigational Site Number : 3480006
🇭🇺Székesfehérvár, Hungary
Azienda Ospedaliera Universitaria Meyer IRCCS-Site Number : 3800003
🇮🇹Florence, Firenze, Italy
Azienda Ospedaliera Universitaria 'Federico II'-Site Number : 3800009
🇮🇹Napoli, Italy
Azienda Ospedaliero-Universitaria Maggiore Della Carità-Site Number : 3800001
🇮🇹Novara, Italy
Investigational Site Number : 3800005
🇮🇹Novara, Italy
University of North Carolina at Chapel Hill- Site Number : 8400001
🇺🇸Chapel Hill, North Carolina, United States
Investigational Site Number : 2500007
🇫🇷Pontoise, France
Investigational Site Number : 3800008
🇮🇹Torette, Ancona, Italy
Investigational Site Number : 6160008
🇵🇱Bialystok, Poland
Investigational Site Number : 6160005
🇵🇱Lodz, Poland
Investigational Site Number : 6160009
🇵🇱Szczecin, Poland
Investigational Site Number : 8260001
🇬🇧Cambridge, Cambridgeshire, United Kingdom
Investigational Site Number : 8260010
🇬🇧Glasgow, Glasgow City, United Kingdom
Investigational Site Number : 8260006
🇬🇧Harrow, London, City Of, United Kingdom
Investigational Site Number : 8260009
🇬🇧Dundee, Scotland, United Kingdom
University of California San Francisco - Mission Bay- Site Number : 8400012
🇺🇸San Francisco, California, United States
University of Colorado - Anschutz Medical Campus- Site Number : 8400003
🇺🇸Aurora, Colorado, United States
University of Florida College of Medicine- Site Number : 8400010
🇺🇸Gainesville, Florida, United States
University of Miami Hospital- Site Number : 8400013
🇺🇸Miami, Florida, United States
AdventHealth Orlando- Site Number : 8400002
🇺🇸Orlando, Florida, United States
Rocky Mountain Diabetes and Osteoporosis Center- Site Number : 8400009
🇺🇸Idaho Falls, Idaho, United States
NorthShore University HealthSystem - Skokie- Site Number : 8400007
🇺🇸Skokie, Illinois, United States
Joslin Diabetes Center - Boston- Site Number : 8400015
🇺🇸Boston, Massachusetts, United States
University at Buffalo-Jacobs School of Medicine and Biomedical Sciences - Jacobs Multiple Sclerosis Center for Treatment and Research- Site Number : 8400004
🇺🇸Buffalo, New York, United States
Cincinnati Children's Hospital Medical Center- Site Number : 8400019
🇺🇸Cincinnati, Ohio, United States
The Children's Hospital of Philadelphia Site Number : 8400005
🇺🇸Philadelphia, Pennsylvania, United States
University of Texas - Southwestern Medical Center- Site Number : 8400011
🇺🇸Dallas, Texas, United States
Benaroya Research Institute at Virginia Mason- Site Number : 8400016
🇺🇸Seattle, Washington, United States
Investigational Site Number : 0560002
🇧🇪Brussels, Belgium
Investigational Site Number : 0560001
🇧🇪Leuven, Belgium
Investigational Site Number : 1240001
🇨🇦Vancouver, British Columbia, Canada
Investigational Site Number : 1240007
🇨🇦London, Ontario, Canada
Investigational Site Number : 1240005
🇨🇦Montreal, Quebec, Canada
Investigational Site Number : 1240004
🇨🇦Montreal, Quebec, Canada
Investigational Site Number : 1240003
🇨🇦Montreal, Quebec, Canada
Investigational Site Number : 2030001
🇨🇿Prague, Czechia
Investigational Site Number : 2500004
🇫🇷Corbeil-essonnes, France
Investigational Site Number : 2500005
🇫🇷Mont-de-marsan, France
Investigational Site Number : 2500006
🇫🇷Paris, France
Investigational Site Number : 2500003
🇫🇷Saint-herblain, France
Investigational Site Number : 2760001
🇩🇪Hannover, Germany
Investigational Site Number : 2760002
🇩🇪Oldenburg in Holstein, Germany
Investigational Site Number : 3480001
🇭🇺Balatonfüred, Hungary
Azienda Socio Sanitaria Territoriale Dei Sette Laghi - Ospedale Filippo del Ponte-Site Number : 3800002
🇮🇹Varese, Italy
Azienda Ospedaliera Universitaria Integrata Verona - Centro regionale di Diabetologia Pediatrica-Site Number : 3800004
🇮🇹Verona, Italy
Investigational Site Number : 6160004
🇵🇱Warsaw, Mazowieckie, Poland
Investigational Site Number : 6160001
🇵🇱Warsaw, Mazowieckie, Poland
Investigational Site Number : 6160007
🇵🇱Warsaw, Mazowieckie, Poland
Investigational Site Number : 7240005
🇪🇸Oviedo, Asturias, Spain
Investigational Site Number : 7240001
🇪🇸Barcelona, Barcelona [Barcelona], Spain
Investigational Site Number : 7240002
🇪🇸Esplugues de Llobregat, Barcelona [Barcelona], Spain
Investigational Site Number : 7240003
🇪🇸Seville, Sevilla, Spain
Investigational Site Number : 7240004
🇪🇸Málaga, Spain
Investigational Site Number : 7240006
🇪🇸Valencia, Spain
Investigational Site Number : 7240007
🇪🇸Vitoria-gasteiz, Álava, Spain
Investigational Site Number : 7520001
🇸🇪Stockholm, Sweden
Investigational Site Number : 7520003
🇸🇪Stockholm, Sweden
Investigational Site Number : 8260003
🇬🇧Birmingham, England, United Kingdom
Investigational Site Number : 8260004
🇬🇧Leicester, Leicestershire, United Kingdom