120 Participants Needed

Siplizumab for Type 1 Diabetes

(DESIGNATE Trial)

Recruiting at 20 trial locations
JG
Overseen ByJason Gaglia, MD, MMSc
Age: < 65
Sex: Any
Trial Phase: Phase 1 & 2
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This is a multicenter, Phase Ib, open-label, siplizumab dose-finding study in individuals aged 8-45 years with a Type 1 diabetes mellitus (T1DM) diagnosis. within 18 months of V0. Participants will be randomized 1:1:1:1 to one of four possible siplizumab dosing arms. All dosing arms will receive weekly siplizumab doses for a total of 12 weeks. After the completion of treatment, participants will undergo follow-up visits at weeks 12, 24, 36 and 52 which include longitudinal MMTTs. If indicated, participants will enter into long-term safety monitoring for up to an additional 48 weeks. Blood samples for mechanistic analyses will be obtained during the treatment phase and thereafter. Adults aged 18- 45 will be enrolled initially at the study sites. The primary objective is to identify a safe, metabolically favorable, dosing regimen for siplizumab in patients with type 1 diabetes that induces changes in T cell phenotypes observed with alefacept therapy in new-onset T1DM. The secondary objectives are to: 1. Assess the safety profile of siplizumab in recently diagnosed T1DM. 2. Assess the effects of siplizumab on residual beta cell function in recently diagnosed T1DM participants.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it excludes those who have used certain medications that affect glucose tolerance or insulin resistance recently. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Siplizumab for Type 1 Diabetes?

There is no direct data on the effectiveness of Siplizumab for Type 1 Diabetes in the provided research. However, similar treatments like anti-CD3 monoclonal antibodies have shown promise in preserving beta-cell function in Type 1 Diabetes, suggesting potential for Siplizumab, which is also an anti-CD3 monoclonal antibody.12345

How is the drug Siplizumab unique for treating Type 1 Diabetes?

Siplizumab is unique because it targets the CD2 receptor on T cells, which is different from other treatments that focus on different immune pathways or cell types. This approach aims to modulate the immune system's attack on insulin-producing cells in the pancreas, offering a novel mechanism compared to existing therapies.13467

Research Team

SG

Stephen Gitelman, M.D.

Principal Investigator

University of California San Francisco, School of Medicine: Diabetes Center

Eligibility Criteria

This trial is for individuals aged 8-45 with Type 1 diabetes diagnosed within the last 18 months. They must have completed their primary COVID-19 vaccination series, not be on certain diabetes or immunosuppressive medications, and cannot have a history of severe reactions to monoclonal antibodies or significant cardiovascular disease.

Inclusion Criteria

I was diagnosed with Type 1 Diabetes less than 18 months ago.
Ability to provide informed consent (parental permission and informed assent of minor, if applicable)
I have diabetes-related antibodies such as GAD-65, Insulin, IA-2, or ZnT8.
See 4 more

Exclusion Criteria

I am not pregnant, breastfeeding, nor planning to become pregnant during the study.
You have had a serious allergic reaction to milk or soy proteins in the past.
I have a history of serious heart problems.
See 14 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly siplizumab doses for a total of 12 weeks

12 weeks
Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including longitudinal MMTTs

40 weeks
Visits at weeks 12, 24, 36, and 52 (in-person)

Long-term safety monitoring

Participants may enter into long-term safety monitoring for up to an additional 48 weeks if indicated

48 weeks

Treatment Details

Interventions

  • Siplizumab
Trial OverviewThe study tests different doses of Siplizumab in patients with Type 1 diabetes. Participants will receive weekly doses for 12 weeks and then be monitored up to one year. The goal is to find a safe dose that affects T cell behavior similar to another therapy (alefacept) and preserves insulin-producing cells.
Participant Groups
8Treatment groups
Experimental Treatment
Group I: Children with T1D 0.22 mg/kg SQ doseExperimental Treatment1 Intervention
Cohort 2 Group 4: 0.22 mg/kg SQ dose for a total of 12 weeks
Group II: Children with T1D 0.18 mg/kg SQ doseExperimental Treatment1 Intervention
Cohort 2 Group 3: 0.18 mg/kg SQ dose for a total of 12 weeks
Group III: Children with T1D 0.12 mg/kg SQ doseExperimental Treatment1 Intervention
Cohort 2 Group 2:0.12 mg/kg SQ dose for a total of 12 weeks
Group IV: Children with T1D 0.08 mg/kg SQ doseExperimental Treatment1 Intervention
Cohort 2 Group 1:0.08 mg/kg SQ dose for a total of 12 weeks
Group V: Adults with T1D 0.22 mg/kg SQ doseExperimental Treatment1 Intervention
Cohort 1 Group 4: 0.22 mg/kg SQ dose for a total of 12 weeks
Group VI: Adults with T1D 0.18 mg/kg SQ doseExperimental Treatment1 Intervention
Cohort 1 Group 3:0.18 mg/kg SQ dose for a total of 12 weeks
Group VII: Adults with T1D 0.12 mg/kg SQ doseExperimental Treatment1 Intervention
Cohort 1 Group 2: 0.12 mg/kg SQ dose for a total of 12 weeks
Group VIII: Adults with T1D 0.08 mg/kg SQ doseExperimental Treatment1 Intervention
Cohort 1 Group1: 0.08 mg/kg SQ dose for a total of 12 weeks

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials
3,361
Recruited
5,516,000+

Findings from Research

In the Phase III DEFEND-2 trial involving 179 patients (including 54 adolescents), otelixizumab did not significantly preserve C-peptide secretion in patients with new-onset Type 1 diabetes, showing a change from baseline that was not statistically significant (P=0.051).
The study found that the efficacy and tolerability of otelixizumab at a 3.1 mg dose were similar to previous results from DEFEND-1, indicating that this dose was ineffective for both adults and adolescents, and further research is needed to explore higher doses and their mechanisms.
Efficacy and safety of low-dose otelixizumab anti-CD3 monoclonal antibody in preserving C-peptide secretion in adolescent type 1 diabetes: DEFEND-2, a randomized, placebo-controlled, double-blind, multi-centre study.Ambery, P., Donner, TW., Biswas, N., et al.[2018]

References

Identification of Sorafenib as a Treatment for Type 1 Diabetes. [2022]
Anti-CD3 monoclonal antibodies in treatment of type 1 diabetes: a systematic review and meta-analysis. [2023]
IL-6 receptor blockade does not slow β cell loss in new-onset type 1 diabetes. [2022]
Efficacy and safety of low-dose otelixizumab anti-CD3 monoclonal antibody in preserving C-peptide secretion in adolescent type 1 diabetes: DEFEND-2, a randomized, placebo-controlled, double-blind, multi-centre study. [2018]
Immunotherapeutic agents in type 1 diabetes: a systematic review and meta-analysis of randomized trials. [2018]
Teplizumab: type 1 diabetes mellitus preventable? [2023]
Combination therapy with saxagliptin and vitamin D for the preservation of β-cell function in adult-onset type 1 diabetes: a multi-center, randomized, controlled trial. [2023]