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

Launched by SANOFI · Jan 31, 2025

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment called SAR442970 for people with recently diagnosed Type 1 Diabetes (T1D), a condition where the body doesn’t produce enough insulin. The goal is to see if this treatment can help preserve the function of insulin-producing cells in the pancreas, which is important for managing diabetes. The trial will involve about 84 participants aged 12 to 35, who will be randomly assigned to receive either the new treatment or a placebo (a harmless substance with no active medication) for one year. This means that some participants will receive the actual treatment while others will receive a dummy treatment, and neither the participants nor the researchers will know who is receiving what during the study.

To be eligible, participants must be diagnosed with Type 1 Diabetes according to specific guidelines and must have started insulin therapy within the last 90 days. They should also have certain markers in their blood that indicate they have T1D. Participants will go through a screening process lasting about 3 to 5 weeks before beginning the treatment, which will last for 52 weeks, followed by a 26-week safety follow-up. It’s important to know that individuals with certain health conditions or histories, such as serious infections or other autoimmune diseases, will not be able to participate. This trial is currently recruiting participants, and anyone interested should consult with their healthcare provider to see if they meet the criteria.

Gender

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Eligibility criteria

• Inclusion Criteria:
• • 1. 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.
• • 2. Participants who meet the criteria of T1D according to American Diabetes Association (ADA 2024).
• • 3. Initiated exogenous insulin replacement therapy not longer than 90 days prior to Screening visit at which random C-peptide will be assessed.
• 4. Receiving insulin hormone replacement therapy:
• 5. 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)
• • 6. Have random C-peptide levels ≥0.2 nmol/L determined at Screening.
• Exclusion Criteria:
• Participants are excluded from the study if any of the following criteria apply:
• • 1. 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.
• • 2. History of invasive opportunistic infections, such as, but not limited to histoplasmosis, listeriosis, coccidioidomycosis, candidiasis, pneumocystis jirovecii, and aspergillosis, regardless of resolution.
• • 3. 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.
• • 4. 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).
• • 5. 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).
• • 6. 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.
• • 7. History of demyelinating disease (including myelitis) or neurologic symptoms suggestive of demyelinating disease.
• • 8. Has other autoimmune or inflammatory conditions
• • 9. 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.
• • 10. 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).
• • 11. Systemic corticosteroids (duration \>7 days), adrenocorticotropic hormone 1 month prior to Screening.
• • 12. 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.
• • 13. 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.
• • 14. Any non-live (inactivated, mRNA, recombinant, conjugate, toxoid) vaccine administered less than 14 days prior to randomization.
• • 15. Any immunosuppressive therapy within 12 weeks prior to randomization and through 78 weeks after randomization
• • 16. Course of Thymoglobulin®, teplizumab or other immunomodulatory treatments at any time
• • 17. 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, sodium-glucose co-transporter-2 and 1 (SGLT2/1) inhibitor, and verapamil within 2 weeks prior to Screening.
• • 18. Abnormal laboratory test(s) at Screening
• • 19. Participants who have impaired renal function with estimated glomerular filtration rate (eGFR) (using the Modification of Diet in Renal Disease \[MDRD\] formula) \<60 mL/min/1.73 m2, or using the bedside Schwartz equation in the participants under the age of 18 y.o.