Frexalimab + Insulin for Type 1 Diabetes

(FABULINUS Trial)

Recruiting at 124 trial locations

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

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Sanofi

Must be taking: Insulin

Must not be taking: Corticosteroids, Immunosuppressives, Biologics, others

Disqualifiers: Infections, Autoimmune diseases, Malignancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

192 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, frexalimab, for individuals with newly diagnosed Type 1 Diabetes (T1D) who are already on insulin. The goal is to determine if frexalimab is safe and effective in managing T1D. Participants will receive one of three doses of frexalimab or a placebo (inactive treatment) while continuing their insulin therapy. This study suits those who have started insulin treatment within the last 90 days and have been diagnosed with T1D. As a Phase 2 trial, this research measures how well the treatment works in an initial, smaller group, offering participants a chance to contribute to important advancements in T1D management.

Do I need to stop taking my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you must be on insulin treatment and cannot take certain diabetes medications like metformin or GLP-1 agonists within 2 weeks before screening. Other medications may be excluded at the investigator's discretion.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that frexalimab, the treatment under study, was safe in earlier trials. A press release about a study lasting almost a year reported that frexalimab was generally well-tolerated, with most participants not experiencing serious side effects. Specifically, participants in that study experienced a lasting decrease in their disease symptoms, suggesting the treatment was both effective and safe. Although further research is ongoing, these early results offer promise for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Type 1 Diabetes?

Researchers are excited about Frexalimab for Type 1 Diabetes because it offers a novel approach compared to traditional insulin therapies. Unlike standard treatments that primarily focus on managing blood sugar levels, Frexalimab targets the immune system, potentially addressing the root cause of Type 1 Diabetes by modulating immune responses. This mechanism could help preserve insulin-producing cells in the pancreas, offering a more comprehensive solution to managing the disease. Additionally, Frexalimab's unique action might lead to fewer side effects and a more sustainable way to control diabetes over time.

What evidence suggests that frexalimab might be an effective treatment for Type 1 Diabetes?

Research has shown that frexalimab might help treat type 1 diabetes. In this trial, participants will receive different doses of frexalimab or a placebo. Earlier trial results suggest frexalimab could be a good option for those newly diagnosed. Early findings indicate that it lowers disease activity and is generally well-tolerated, meaning patients don't experience severe side effects. This treatment targets a protein called CD40L, part of the immune system, which might help stop the body from attacking its own insulin-producing cells. While more information is needed, these early results are promising for those considering this treatment. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

The FABULINUS trial is for young individuals with newly diagnosed Type 1 Diabetes. Participants must be between 12-21 years old, vaccinated according to local schedules, and have started insulin therapy within the last 90 days. They should test positive for certain diabetes-related autoantibodies and agree to use contraception.

Inclusion Criteria

I started using insulin less than 90 days ago.

I have at least one type 1 diabetes autoantibody (GAD-65, IA-2, ZnT8, or Insulin).

I am vaccinated as per my local schedule and followed the required waiting period before joining the trial.

Exclusion Criteria

I haven't had serious infections or been hospitalized for infections in the last 30 days.

I have had serious infections like histoplasmosis or candidiasis.

I have been tested for TB using blood tests or other methods.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

3-5 weeks

Treatment

Participants receive frexalimab or placebo for 52 weeks in a double-blind manner

52 weeks

Blinded Extension

Participants continue to receive frexalimab or placebo for an additional 52 weeks

52 weeks

Safety Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 26 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Frexalimab

Trial Overview This study tests Frexalimab's safety and effectiveness in preserving natural insulin production compared to a placebo in youths on standard insulin treatment. It's a double-blind Phase 2 trial with two parts: initial dose safety assessment followed by dose-finding over up to 104 weeks of treatment.

How Is the Trial Designed?

Group I: Frexalimab Dose 3 Experimental Treatment 2 Interventions

Group II: Frexalimab Dose 2 Experimental Treatment 2 Interventions

Group III: Frexalimab Dose 1 Experimental Treatment 2 Interventions

Group IV: Placebo Placebo Group 2 Interventions

Matching Placebo

Who Is Running the Clinical Trial?

Sanofi

Lead Sponsor

Trials

2,246

Recruited

4,085,000+

Paul Hudson

Sanofi

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Christopher Corsico

Sanofi

Chief Medical Officer

MD from Cornell University, MPH in Chronic Disease Epidemiology from Yale University

Published Research Related to This Trial

In a study of 23 patients with type 1 diabetes, high levels of insulin antibodies were associated with a threefold increase in total insulin aspart levels, indicating that insulin antibodies can significantly affect insulin pharmacokinetics.

Despite the increased total insulin levels in patients with high insulin antibodies, there were no significant differences in insulin pharmacodynamics or long-term glycemic control (HbA1C levels) between patients with moderate and high antibody levels, suggesting that the presence of insulin antibodies does not adversely impact overall diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of insulin antibodies on insulin aspart pharmacokinetics and pharmacodynamics after 12-week treatment with multiple daily injections of biphasic insulin aspart 30 in patients with type 1 diabetes. Chen, JW., Frystyk, J., Lauritzen, T., et al.[2016]

Basal insulin Fc (BIF) demonstrated a long half-life of approximately 17 days, allowing for once-weekly dosing while effectively reducing fasting blood glucose levels for at least 5 days without severe hypoglycemia.

In a 6-week study involving 33 participants with type 2 diabetes, BIF showed a consistent glucose control profile similar to insulin glargine, indicating it is well tolerated and has a favorable pharmacokinetic and pharmacodynamic profile for further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic and pharmacodynamic properties of the novel basal insulin Fc (insulin efsitora alfa), an insulin fusion protein in development for once-weekly dosing for the treatment of patients with diabetes. Heise, T., Chien, J., Beals, JM., et al.[2023]

In an open-label study of 298 people with Type 1 diabetes, switching to insulin glargine 300 units/ml (U300) resulted in a significant reduction in HbA1c levels by an average of 4 mmol/mol (-0.4%) after 6 months, indicating improved blood sugar control.

The study found no significant increase in severe hypoglycaemic episodes or diabetic ketoacidosis events after starting U300, suggesting that it is a safe option for managing Type 1 diabetes without increasing the risk of serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicentre, UK, retrospective, observational study to assess the effectiveness of insulin glargine 300 units/ml in treating people with Type 1 diabetes mellitus in routine clinical practice (SPARTA). Pang, T., Bain, SC., Black, RNA., et al.[2022]

In a study of 47 patients with type 1 diabetes, the development of insulin antibodies (IABs) from using inhaled insulin did not negatively affect postprandial glucose tolerance or the duration of insulin action over 24 weeks.

Both inhaled insulin and subcutaneous insulin showed similar effectiveness in managing blood glucose levels, and no adverse events were linked to the presence of IABs, indicating that inhaled insulin is a safe alternative for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of insulin antibodies on the metabolic action of inhaled and subcutaneous insulin: a prospective randomized pharmacodynamic study. Heise, T., Bott, S., Tusek, C., et al.[2019]

Insulin glargine 300 U/mL (Gla-300) provides glycemic control similar to that of the standard Gla-100, with a mean reduction in glycated hemoglobin A1c of -1.02% in a meta-analysis of over 2400 patients with type 1 and type 2 diabetes.

Gla-300 is associated with a lower risk of nocturnal hypoglycemia (relative risk of 0.75) and potentially less weight gain compared to Gla-100, making it a promising alternative for long-acting insulin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Insulin Glargine 300 U/mL for the Treatment of Type 1 and Type 2 Diabetes Mellitus. Goldman, J., White, JR.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04879628

NCT04879628 | Proof-of-concept Study for SAR441344 ... Primary Objective: To determine the efficacy of SAR441344 as measured by reduction of the number of new active brain lesions. Secondary Objective:.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11623868/

Frexalimab (SAR441344) as a potential multiautoimmune ... Trial results have shown that frexalimab is a better treatment choice for newly diagnosed type 1 diabetes mellitus (DM) patients. Amongst first-generation and ...

3. go.drugbank.com go.drugbank.com/drugs/DB18926

Frexalimab: Uses, Interactions, Mechanism of Action Frexalimab is under investigation in clinical trial NCT06141486 (Efficacy and Safety Study of Frexalimab (SAR441344) in Adults With Nonrelapsing ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06141473

NCT06141473 | Efficacy and Safety Studies of Frexalimab ... The purpose of each study is to independently measure the annualized relapse rate (ARR) with administration of frexalimab compared to a daily oral dose of ...

5. sanofi.com sanofi.com/en/media-room/press-releases/2024/2024-04-17-05-00-00-2864225

Press Release: New 48-week frexalimab phase 2 data ... Sanofi's CD40L antibody, frexalimab, demonstrated sustained reduction of disease activity and favorable tolerability after nearly one year in participants with ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06141486

NCT06141486 | Efficacy and Safety Study of Frexalimab ... The purpose of this randomized, double-blind, placebo-controlled, parallel group study is to determine the efficacy of frexalimab in delaying the disability ...