Frexalimab + Insulin for Type 1 Diabetes

(FABULINUS Trial)

Recruiting at76 trial locations

Age: < 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Sanofi

Must be taking: Insulin

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

Disqualifiers: Infections, Autoimmune diseases, Malignancy, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called frexalimab in young people with newly diagnosed Type 1 Diabetes. The goal is to see if it can help their bodies keep making insulin. The study will compare different doses of the drug to find the safest and most effective amount.

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.

What makes the drug Frexalimab unique for treating Type 1 Diabetes?

Frexalimab is unique because it combines with insulin to potentially offer a novel approach to managing Type 1 Diabetes, although specific details about its mechanism or benefits compared to existing treatments are not provided in the available research. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Frexalimab (Monoclonal Antibodies)

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

The effect of insulin antibodies on the metabolic action of inhaled and subcutaneous insulin: a prospective randomized pharmacodynamic study. [2019]

2. England 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. [2023]

3. England 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). [2022]

4. England 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. [2016]

5. United States pubmed.ncbi.nlm.nih.gov

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