Treatment of Type 1 Diabetes With Anti-OX40L Bispecific With Anti-TNF Activity In a Single Nanobody® Molecule

NCT06812988 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: ACT18368U1111-1307-7268
• Study Type: interventional
• Target: 84
• Locations: 8 countries
• Sites: 24

Brief Summary

This is a randomized, placebo-controlled, parallel group, multicenter, double-blind Phase 2a, 2-arm study. The goal of this Phase 2a study is to assess safety and efficacy of brivekimig in comparison to placebo to preserve β-cell function in participants with recently diagnosed Stage 3 type 1 diabetes (T1D) on insulin therapy. The study design comprises 2 parts: in Part A adult participants (18 to 35 years of age at screening) and in Part B adolescent and young adult participants (age range 12 to 21 years) will be randomized into brivekimig and placebo groups. Approximately 84 participants will be included with randomization ratio 3:1 (active:placebo). The study includes a screening period (3 to 5 weeks), a double-blind treatment period of 52 weeks and a safety follow-up of 26 weeks.

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change from baseline to Week 26 in mean 2-hour mixed meal tolerance test (MMTT) stimulated C-peptide concentration

  Mixed meal tolerance test MMTT stimulated C-peptide concentration is to be calculated from area under the concentration-time curve (AUC)

  From Baseline to Week 26

Secondary Outcomes (15)

• Change from baseline to Week 52 in mean 2-hour MMTT stimulated Cpeptide concentration

  From Baseline to Week 52

• Participant remaining C-peptide positive at Week 26 and Week 52

  Week 26 and Week 52

• Time in range (TIR) (70-180 mg/dL) at Week 26 and Week 52

  Week 26 and Week 52

• Change from baseline to Week 26 and Week 52 in insulin dose

  From Baseline to Week 26 and Week 52

• Change from baseline to Week 26 and Week 52 in glycated hemoglobin A1c (HbA1c) level

  From Baseline to Week 26 and Week 52

Study Arms (2)

Brivekimig

EXPERIMENTAL

Participants will receive subcutaneous injection of brivekimig.

Drug: Brivekimig

Placebo

PLACEBO COMPARATOR

Participants will receive subcutaneous injection of matching placebo.

Drug: Placebo

Interventions

Placebo DRUG

Pharmaceutical form: Solution Route of administration: Subcutaneous injection

Placebo

Brivekimig DRUG

Pharmaceutical form: Solution Route of administration: Subcutaneous injection

Brivekimig

Eligibility Criteria

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

You may qualify if:

• Participant must be 18 to 35 y.o. inclusive, at the time of signing the informed consent in order to be enrolled in Part A. Participant must be 12 to 21 y.o. inclusive, at the time of signing the informed consent in order to be enrolled in Part B.
• Participants who meet the criteria of T1D according to American Diabetes Association (ADA 2024).
• Initiated exogenous insulin replacement therapy not longer than 90 days prior to Screening visit at which random C-peptide will be assessed.
• Receiving insulin hormone replacement therapy:
• 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.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Serious systemic viral, bacterial or fungal infection (eg, pneumonia, pyelonephritis), infection requiring hospitalization or intravenous (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.
• 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.
• 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 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).
• History of moderate to severe congestive heart failure (New York Health Association \[NYHA\] Class III or IV), or recent cerebrovascular accident, or any other condition which, in the opinion of the Investigator, would put the participant at risk by participation in the protocol.
• History of demyelinating disease (including myelitis) or neurologic symptoms suggestive of demyelinating disease.
• Has other autoimmune or inflammatory conditions
• Diabetes of forms other than autoimmune T1D that include but are 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 judgment of the investigator.
• History of malignancy or lymphoproliferative disease other than adequately treated localized carcinoma in situ of the cervix or nonmetastatic squamous cell carcinoma, or nonmetastatic basal cell carcinoma of the skin that was excised and completely cured or any family history in two or more relatives (immediate family) of same cancer (ie, rare cancers, those manifesting at a young age in a parent or sibling, certain genetic-based inheritable cancers).
• Systemic corticosteroids (duration \>7 days), adrenocorticotropic hormone 1 month prior to Screening.
• Any IV, intramuscular (IM) or SC administered biologic treatments (mono- or polyclonal antibodies affecting function of immune system), \<3 months or \<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 or is scheduled in expected period of study (78 weeks after randomization) if this vaccination cannot be safely postponed.
• Any non-live (inactivated, mRNA, recombinant, conjugate, toxoid) vaccine administered less than 14 days prior to randomization.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (24)

Atlanta Diabetes Associates- Site Number : 8400006

Atlanta, Georgia, 30318, United States

Location

IACT Health - Columbus - Talbotton Road- Site Number : 8400012

Columbus, Georgia, 31904, United States

Location

Profound Research - MHP - TriAtria- Site Number : 8400015

Farmington Hills, Michigan, 48334, United States

Location

Tekton Research - McKinney- Site Number : 8400017

McKinney, Texas, 75069, United States

Location

Advanced Research Institute - Odgen- Site Number : 8400007

Ogden, Utah, 84405, United States

Location

Investigational Site Number : 0320001

Buenos Aires, 1119, Argentina

Location

Investigational Site Number : 0320002

Buenos Aires, 1178, Argentina

Location

Investigational Site Number : 0320005

Buenos Aires, 1180, Argentina

Location

Investigational Site Number : 0320004

Buenos Aires, 1419, Argentina

Location

Investigational Site Number : 0320003

Salta, 4400, Argentina

Location

Investigational Site Number : 0360003

Saint Leonards, New South Wales, 2065, Australia

Location

Investigational Site Number : 0360002

Brisbane, Queensland, 4029, Australia

Location

Investigational Site Number : 0360001

Parkville, Victoria, 3050, Australia

Location

Centro de Diabetes Curitiba- Site Number : 0760005

Curitiba, Paraná, 80810-040, Brazil

Location

Centro de Pesquisas Clínicas - São Paulo- Site Number : 0760002

São Paulo, 01228-200, Brazil

Location

Investigational Site Number : 1240006

Surrey, British Columbia, V3T 2V6, Canada

Location

Investigational Site Number : 1240001

Vancouver, British Columbia, V5Y 3W2, Canada

Location

Investigational Site Number : 1520003

Providencia, Reg Metropolitana de Santiago, 7500000, Chile

Location

Investigational Site Number : 1520001

Santiago, Reg Metropolitana de Santiago, 7500505, Chile

Location

Investigational Site Number : 1520004

Concepción, Región del Biobío, 4070566, Chile

Location

Investigational Site Number : 3760001

Jerusalem, 9112001, Israel

Location

Investigational Site Number : 3760003

Kefar Sava, 4428164, Israel

Location

Investigational Site Number : 3760002

Ramat Gan, 5262100, Israel

Location

Investigational Site Number : 6820002

Riyadh, 12713, Saudi Arabia

Location

Related Links

• ACT18368 Plain Language Results Summary

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: January 31, 2025
• First Posted: February 6, 2025
• Study Start: February 28, 2025
• Primary Completion (Estimated): April 29, 2027
• Study Completion (Estimated): April 29, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

CL (3); BR (2); AU (3); CA (2); IL (3); SA (1); US (5); AR (5)