Clinical trial NCT06111586: FrexalimAB in Preservation of Endogenous insULIN Secretion Compared to Placebo in adUlts and Adolescents on Top of inSulin Therapy (FABULINUS)
Official title: A 52-week Randomized, Double-blind, Placebo-controlled, Multi-center Phase 2b Study With a 52-week Blinded Extension Assessing Safety and Efficacy of Frexalimab, a CD40L-antagonist Monoclonal Antibody, for Preservation of Pancreatic β-cell Function in Adults and Adolescents With Newly Diagnosed Type 1 Diabetes on Insulin Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2023-11-01
Enrollment: 192
Sex: ALL
Minimum age (years): 12
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Change from baseline to W52 in mean 2h mixed meal tolerance test (MMTT) stimulated C-peptide concentration
timeFrame: Baseline to Week 52
Secondary outcomes:
measure: Time in range (70-180 mg/dL), assessed by CGM at W52 and W104
timeFrame: At Week 52 and Week 104
measure: Proportion of participants who remain C-peptide positive (mean 2h MMTT stimulated C-peptide concentration ≥0.2 nmol/L) at W52 and W104
timeFrame: At Week 52 and Week 104
measure: Proportion of participants with reduction from baseline to W52 and W104 of less than 10% in mean 2h MMTT stimulated C-peptide concentration
timeFrame: From baseline to Week 52 and Week 104
measure: 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])
timeFrame: At Week 52 and Week 104
measure: Change from baseline to W52 and W104 in insulin dose [IU/kg/day]
timeFrame: From baseline to Week 52 and Week 104
measure: HbA1c level and its change from baseline at W52 and W104
timeFrame: From baseline to Week 52 and Week 104
measure: Proportion of participants with HbA1c ≤6.5% and requiring no injections of exogenous insulin at W52 and W104
timeFrame: At Week 52 and Week 104
measure: Proportion of participants with HbA1c ≤6.5% and requiring ≤0.25 IU of insulin at W52 and W104
timeFrame: At Week 52 and Week 104
measure: Proportion of participants with HbA1c <7% at W52 and W104
timeFrame: At Week 52 and Week 104
measure: Incidence of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs) and TEAEs leading to treatment discontinuation
timeFrame: Until Week 130
measure: Number of participants with at least one hypoglycemic event
timeFrame: Until Week 130
measure: Number of participants with at least one hyperglycemic episode
timeFrame: Until Week 130
measure: Number of participants with at least one diabetic ketoacidosis (DKA) event
timeFrame: Until Week 130
measure: Number of participants with clinically significant changes in vital signs, electrocardiogram (ECG), and/or laboratory evaluation
timeFrame: Until Week 130
measure: Height and growth rate over time (for participants <18 y.o. at screening)
timeFrame: Until Week 130
measure: Frexalimab plasma concentrations over time
timeFrame: Until Week 104
measure: Incidence of anti-drug antibodies (ADAs) over time
timeFrame: Until Week 130
measure: Change from baseline to W52 and W104 in PedsQL Diabetes Symptoms domain score (all participants)
timeFrame: From baseline to Week 52 and Week 104
measure: Change from baseline to W52 and W104 in Pediatric Quality of Life (PedsQL) Diabetes Management domain score (all participants)
timeFrame: From baseline to Week 52 and Week 104
measure: Change from baseline to W52 and W104 in Problem Areas In Diabetes (PAID) total score (all participants)
timeFrame: From baseline to Week 52 and Week 104
measure: Change from baseline to W52 and W104 in Diabetes Treatment Satisfaction Questionnaires (DTSQs) total and item scores (all participants)
timeFrame: From baseline to Week 52 and Week 104
measure: Change from baseline to W52 and W104 in PAID immediate and theoretical domain scores (caregivers of all participants 12-17 y.o.)
timeFrame: From baseline to Week 52 and Week 104
measure: Change from baseline to W52 and W104 in DTSQs Total and item scores (caregivers of all participants 12-17 y.o.)
timeFrame: From baseline to Week 52 and Week 104
measure: Time in tight range (TITR, 70 - 140 mg/dL), assessed by CGM at W52 and W104
timeFrame: Time in tight range (TITR, 70 - 140 mg/dL), assessed by CGM at W52 and W104
measure: Change from baseline to W104 in mean 2h mixed meal tolerance test (MMTT) stimulated C-peptide concentration, calculated from AUC
timeFrame: From baseline to Week 104
measure: Change from baseline to W52 in IDAA1c score
timeFrame: From baseline to Week 52
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco - Mission Bay- Site Number : 8400012
state: California
city: Aurora
country: United States
facility: University of Colorado - Anschutz Medical Campus- Site Number : 8400003
state: Colorado
city: Gainesville
country: United States
facility: University of Florida College of Medicine- Site Number : 8400010
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital- Site Number : 8400013
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando- Site Number : 8400002
state: Florida
city: Idaho Falls
country: United States
facility: Rocky Mountain Diabetes and Osteoporosis Center- Site Number : 8400009
state: Idaho
city: Skokie
country: United States
facility: NorthShore University HealthSystem - Skokie- Site Number : 8400007
state: Illinois
city: Boston
country: United States
facility: Joslin Diabetes Center - Boston- Site Number : 8400015
state: Massachusetts
city: Buffalo
country: United States
facility: University at Buffalo-Jacobs School of Medicine and Biomedical Sciences - Jacobs Multiple Sclerosis Center for Treatment and Research- Site Number : 8400004
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill- Site Number : 8400001
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center- Site Number : 8400019
state: Ohio
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia Site Number : 8400005
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas - Southwestern Medical Center- Site Number : 8400011
state: Texas
city: Seattle
country: United States
facility: Benaroya Research Institute at Virginia Mason- Site Number : 8400016
state: Washington
city: Brussels
country: Belgium
facility: Investigational Site Number : 0560002
city: Leuven
country: Belgium
facility: Investigational Site Number : 0560001
city: Vancouver
country: Canada
facility: Investigational Site Number : 1240001
state: British Columbia
city: London
country: Canada
facility: Investigational Site Number : 1240007
state: Ontario
city: Montreal
country: Canada
facility: Investigational Site Number : 1240005
state: Quebec
city: Montreal
country: Canada
facility: Investigational Site Number : 1240004
state: Quebec
city: Montreal
country: Canada
facility: Investigational Site Number : 1240003
state: Quebec
city: Ostrava
country: Czechia
facility: Investigational Site Number : 2030003
city: Prague
country: Czechia
facility: Investigational Site Number : 2030002
city: Prague
country: Czechia
facility: Investigational Site Number : 2030001
city: Corbeil-essonnes
country: France
facility: Investigational Site Number : 2500004
city: Mont-de-marsan
country: France
facility: Investigational Site Number : 2500005
city: Paris
country: France
facility: Investigational Site Number : 2500006
city: Pontoise
country: France
facility: Investigational Site Number : 2500007
city: Saint-herblain
country: France
facility: Investigational Site Number : 2500003
city: Hannover
country: Germany
facility: Investigational Site Number : 2760001
city: Oldenburg in Holstein
country: Germany
facility: Investigational Site Number : 2760002
city: Ulm
country: Germany
facility: Investigational Site Number : 2760004
city: Balatonfüred
country: Hungary
facility: Investigational Site Number : 3480001
city: Nyíregyháza
country: Hungary
facility: Investigational Site Number : 3480002
city: Székesfehérvár
country: Hungary
facility: Investigational Site Number : 3480006
city: Torette
country: Italy
facility: Investigational Site Number : 3800008
state: Ancona
city: Florence
country: Italy
facility: Azienda Ospedaliera Universitaria Meyer IRCCS-Site Number : 3800003
state: Firenze
city: Milan
country: Italy
facility: IRCCS Ospedale San Raffaele-Site Number : 3800006
state: Milano
city: Caserta
country: Italy
facility: Azienda Ospedaliera Universitaria 'Federico II'-Site Number : 3800009
city: Novara
country: Italy
facility: Azienda Ospedaliero-Universitaria Maggiore Della Carità-Site Number : 3800001
city: Varese
country: Italy
facility: Azienda Socio Sanitaria Territoriale Dei Sette Laghi - Ospedale Filippo del Ponte-Site Number : 3800002
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona - Centro regionale di Diabetologia Pediatrica-Site Number : 3800004
city: Warsaw
country: Poland
facility: Investigational Site Number : 6160004
state: Mazowieckie
city: Warsaw
country: Poland
facility: Investigational Site Number : 6160001
state: Mazowieckie
city: Warsaw
country: Poland
facility: Investigational Site Number : 6160007
state: Mazowieckie
city: Bialystok
country: Poland
facility: Investigational Site Number : 6160008
city: Lodz
country: Poland
facility: Investigational Site Number : 6160005
city: Szczecin
country: Poland
facility: Investigational Site Number : 6160009
city: Warszawa
country: Poland
facility: Investigational Site Number : 6160006
city: Oviedo
country: Spain
facility: Investigational Site Number : 7240005
state: Asturias
city: Barcelona
country: Spain
facility: Investigational Site Number : 7240001
state: Barcelona [Barcelona]
city: Esplugues de Llobregat
country: Spain
facility: Investigational Site Number : 7240002
state: Barcelona [Barcelona]
city: Seville
country: Spain
facility: Investigational Site Number : 7240003
state: Sevilla
city: Málaga
country: Spain
facility: Investigational Site Number : 7240004
city: Valencia
country: Spain
facility: Investigational Site Number : 7240006
city: Vitoria-gasteiz
country: Spain
facility: Investigational Site Number : 7240007
state: Álava
city: Solna
country: Sweden
facility: Investigational Site Number : 7520002
city: Stockholm
country: Sweden
facility: Investigational Site Number : 7520001
city: Stockholm
country: Sweden
facility: Investigational Site Number : 7520003
city: Cambridge
country: United Kingdom
facility: Investigational Site Number : 8260001
state: Cambridgeshire
city: Birmingham
country: United Kingdom
facility: Investigational Site Number : 8260003
state: England
city: Birmingham
country: United Kingdom
facility: Investigational Site Number : 8260007
state: England
city: Glasgow
country: United Kingdom
facility: Investigational Site Number : 8260010
state: Glasgow City
city: Leicester
country: United Kingdom
facility: Investigational Site Number : 8260004
state: Leicestershire
city: Harrow
country: United Kingdom
facility: Investigational Site Number : 8260006
state: London, City Of
city: Dundee
country: United Kingdom
facility: Investigational Site Number : 8260009
state: Scotland
Study officials:
References: