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

NCT06111586 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: DRI17476U1111-1275-96182022-500531-36
• Study Type: interventional
• Target: 192
• Locations: 16 countries
• Sites: 80

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 Optional Open Label Extension: 104 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.

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change from baseline to W52 in mean 2h mixed meal tolerance test (MMTT) stimulated C-peptide concentration

  mixed meal tolerance test (MMTT) stimulated C-peptide concentration is to be calculated from AUC

  Baseline to Week 52

Secondary Outcomes (26)

• 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

• 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

• 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

Study Arms (4)

Frexalimab Dose 1

EXPERIMENTAL

Drug: Frexalimab; Drug: Insulin

Frexalimab Dose 2

EXPERIMENTAL

Drug: Frexalimab; Drug: Insulin

Frexalimab Dose 3

EXPERIMENTAL

Drug: Frexalimab; Drug: Insulin

Placebo

PLACEBO COMPARATOR

Matching Placebo

Drug: Placebo; Drug: Insulin

Interventions

Frexalimab DRUG

Intravenous (IV) Infusion at Day 1 and subcutaneous (SC) Injection from W2 to W102

Frexalimab Dose 1; Frexalimab Dose 2; Frexalimab Dose 3

Placebo DRUG

IV Infusion at Day 1 and SC Injection from W2 to W102

Placebo

Insulin DRUG

SC injection, dose and frequency will be established and/or adjusted by investigator

Frexalimab Dose 1; Frexalimab Dose 2; Frexalimab Dose 3; Placebo

Eligibility Criteria

• Age: 12 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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), that require treatment with biologic drugs (mono or polyclonal antibodies) or systemic corticosteroid therapy (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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (80)

University of California San Francisco - Mission Bay- Site Number : 8400012

San Francisco, California, 94158, United States

RECRUITING

University of Colorado - Anschutz Medical Campus- Site Number : 8400003

Aurora, Colorado, 80045, United States

RECRUITING

University of Florida College of Medicine- Site Number : 8400010

Gainesville, Florida, 32610, United States

RECRUITING

University of Miami Hospital- Site Number : 8400013

Miami, Florida, 33136, United States

RECRUITING

AdventHealth Orlando- Site Number : 8400002

Orlando, Florida, 32803, United States

RECRUITING

Rocky Mountain Diabetes and Osteoporosis Center- Site Number : 8400009

Idaho Falls, Idaho, 83404, United States

RECRUITING

NorthShore University Health System - Endeavor Health Medical Group - Skokie - Woods Drive- Site Number : 8400007

Skokie, Illinois, 60077, United States

RECRUITING

Joslin Diabetes Center - Boston- Site Number : 8400015

Boston, Massachusetts, 02215, United States

RECRUITING

University at Buffalo - Downtown Campus- Site Number : 8400004

Buffalo, New York, 14203, United States

RECRUITING

University of North Carolina at Chapel Hill- Site Number : 8400001

Chapel Hill, North Carolina, 27514, United States

RECRUITING

Cincinnati Children's Hospital Medical Center- Site Number : 8400019

Cincinnati, Ohio, 45229, United States

RECRUITING

The Children's Hospital of Philadelphia Site Number : 8400005

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Texas - Southwestern Medical Center- Site Number : 8400011

Dallas, Texas, 75390, United States

RECRUITING

Benaroya Research Institute at Virginia Mason- Site Number : 8400016

Seattle, Washington, 98101, United States

RECRUITING

Investigational Site Number : 0400002

Graz, 8036, Austria

RECRUITING

Investigational Site Number : 0400004

Linz, 4020, Austria

RECRUITING

Investigational Site Number : 0400001

Vienna, 1090, Austria

RECRUITING

Investigational Site Number : 0560002

Brussels, 1090, Belgium

RECRUITING

Investigational Site Number : 0560001

Leuven, 3000, Belgium

RECRUITING

Investigational Site Number : 1240001

Vancouver, British Columbia, V5Y 3W2, Canada

RECRUITING

Investigational Site Number : 1240007

London, Ontario, N6A 5W9, Canada

RECRUITING

Investigational Site Number : 1240005

Montreal, Quebec, H3T 1C5, Canada

RECRUITING

Investigational Site Number : 1240004

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Investigational Site Number : 1240003

Montreal, Quebec, H4A 3T2, Canada

RECRUITING

Investigational Site Number : 2030003

Ostrava, 708 52, Czechia

RECRUITING

Investigational Site Number : 2030002

Prague, 100 34, Czechia

RECRUITING

Investigational Site Number : 2030001

Prague, 150 06, Czechia

RECRUITING

Investigational Site Number : 2080005

Herlev, 2730, Denmark

RECRUITING

Investigational Site Number : 2460001

Helsinki, 00290, Finland

RECRUITING

Investigational Site Number : 2460004

Oulu, 90220, Finland

RECRUITING

Investigational Site Number : 2460003

Tampere, 33520, Finland

RECRUITING

Investigational Site Number : 2460002

Turku, 20521, Finland

RECRUITING

Investigational Site Number : 2500004

Corbeil-Essonnes, 91106, France

RECRUITING

Investigational Site Number : 2500005

Mont-de-Marsan, 40024, France

RECRUITING

Investigational Site Number : 2500006

Paris, 75679, France

RECRUITING

Investigational Site Number : 2500007

Pontoise, 95300, France

RECRUITING

Investigational Site Number : 2500003

Saint-Herblain, 44800, France

RECRUITING

Investigational Site Number : 2760003

Dresden, 01307, Germany

RECRUITING

Investigational Site Number : 2760001

Hanover, 30173, Germany

RECRUITING

Investigational Site Number : 2760002

Oldenburg in Holstein, 23758, Germany

RECRUITING

Investigational Site Number : 2760004

Ulm, 89081, Germany

RECRUITING

Investigational Site Number : 3480001

Balatonfüred, 8230, Hungary

RECRUITING

Investigational Site Number : 3480004

Budapest, 1089, Hungary

RECRUITING

Investigational Site Number : 3480002

Nyíregyháza, 4400, Hungary

RECRUITING

Investigational Site Number : 3480003

Nyíregyháza, 4400, Hungary

RECRUITING

Investigational Site Number : 3480006

Székesfehérvár, 8000, Hungary

RECRUITING

AOU delle Marche - Ospedale G. Salesi-Site Number : 3800008

Torette, Ancona, 60020, Italy

RECRUITING

Azienda Ospedaliera Universitaria Meyer IRCCS-Site Number : 3800003

Florence, Firenze, 50139, Italy

ACTIVE NOT RECRUITING

IRCCS Ospedale San Raffaele-Site Number : 3800006

Milan, Milano, 20132, Italy

RECRUITING

Azienda Ospedaliera Universitaria 'Federico II'-Site Number : 3800009

Naples, Napoli, 80131, Italy

ACTIVE NOT RECRUITING

Ospedale Pediatrico Bambin Gesu IRCCS-Site Number : 3800007

Rome, Roma, 00165, Italy

ACTIVE NOT RECRUITING

Azienda Ospedaliero-Universitaria Maggiore Della Carità-Site Number : 3800001

Novara, 28100, Italy

RECRUITING

Azienda Socio Sanitaria Territoriale Dei Sette Laghi - Ospedale Filippo del Ponte-Site Number : 3800002

Varese, 21100, Italy

COMPLETED

Azienda Ospedaliera Universitaria Integrata Verona - Centro regionale di Diabetologia Pediatrica-Site Number : 3800004

Verona, 37126, Italy

RECRUITING

Investigational Site Number : 6160005

Lodz, Lódzkie, 92-213, Poland

RECRUITING

Investigational Site Number : 6160006

Warsaw, Masovian Voivodeship, 02-097, Poland

RECRUITING

Investigational Site Number : 6160004

Warsaw, Masovian Voivodeship, 02-117, Poland

RECRUITING

Investigational Site Number : 6160001

Warsaw, Masovian Voivodeship, 02-507, Poland

RECRUITING

Investigational Site Number : 6160007

Warsaw, Masovian Voivodeship, 04-746, Poland

RECRUITING

Investigational Site Number : 6160008

Bialystok, Podlaskie Voivodeship, 15-274, Poland

RECRUITING

Investigational Site Number : 6160002

Katowice, Silesian Voivodeship, 40-752, Poland

RECRUITING

Investigational Site Number : 6160009

Szczecin, West Pomeranian Voivodeship, 71-252, Poland

RECRUITING

Investigational Site Number : 7050001

Ljubljana, 1000, Slovenia

RECRUITING

Investigational Site Number : 7240001

Barcelona, Barcelona [Barcelona], 08035, Spain

RECRUITING

Investigational Site Number : 7240002

Esplugues de Llobregat, Barcelona [Barcelona], 08950, Spain

RECRUITING

Investigational Site Number : 7240005

Oviedo, Principality of Asturias, 33011, Spain

RECRUITING

Investigational Site Number : 7240003

Seville, Sevilla, 41009, Spain

RECRUITING

Investigational Site Number : 7240004

Málaga, 29010, Spain

RECRUITING

Investigational Site Number : 7240006

Valencia, 46010, Spain

RECRUITING

Investigational Site Number : 7240007

Vitoria-Gasteiz, Álava, 01009, Spain

RECRUITING

Investigational Site Number : 7520002

Solna, 171 64, Sweden

RECRUITING

Investigational Site Number : 7520001

Stockholm, 113 65, Sweden

RECRUITING

Investigational Site Number : 7520003

Stockholm, 118 83, Sweden

RECRUITING

Investigational Site Number : 8260001

Cambridge, Cambridgeshire, CB2 2QQ, United Kingdom

ACTIVE NOT RECRUITING

Investigational Site Number : 8260009

Dundee, Dundee City, DD1 9SY, United Kingdom

RECRUITING

Investigational Site Number : 8260003

Birmingham, England, B15 2TH, United Kingdom

RECRUITING

Investigational Site Number : 8260007

Birmingham, England, B4 6NH, United Kingdom

ACTIVE NOT RECRUITING

Investigational Site Number : 8260010

Glasgow, Glasgow City, G51 4TF, United Kingdom

ACTIVE NOT RECRUITING

Investigational Site Number : 8260004

Leicester, Leicestershire, LE5 4PW, United Kingdom

RECRUITING

Investigational Site Number : 8260006

Harrow, London, City of, HA1 3UJ, United Kingdom

ACTIVE NOT RECRUITING

Related Links

• DRI17476 Plain Language Results Summary

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Insulin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Central Study Contacts

Trial Transparency email recommended (Toll free number for US & Canada)

CONTACT

800-633-1610; contact-us@sanofi.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2023
• First Posted: November 1, 2023
• Study Start: December 11, 2023
• Primary Completion (Estimated): April 28, 2027
• Study Completion (Estimated): October 29, 2030
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

CA (5); SE (3); GB (7); ES (7); PL (8); DE (4); CZ (3); DK (1); BE (2); FR (5); AU (3); US (14); IT (8); SL (1); FI (4); HU (5)