Siplizumab for Type 1 Diabetes

(DESIGNATE Trial)

No longer recruiting at 20 trial locations

Overseen By Jason Gaglia, MD, MMSc

Age: < 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Atypical antipsychotics, Glucocorticoids, others

Disqualifiers: Infections, Malignancy, Autoimmune diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 12

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, siplizumab (also known as MEDI-507 or TCD 601), for individuals diagnosed with Type 1 diabetes in the past 18 months. The goal is to identify a safe and effective dose that manages the immune system's attack on insulin-producing cells, a hallmark of this condition. Participants will join one of several dosing groups to determine the most effective option. This trial suits those recently diagnosed with Type 1 diabetes who have at least one diabetes-related antibody. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that siplizumab has been studied in adults recently diagnosed with type 1 diabetes to improve the function of beta cells, which are crucial for insulin production. Although detailed safety information for type 1 diabetes is limited, this treatment remains in the early testing stages. Consequently, information about its safety for people with type 1 diabetes is still scarce.

The current trial is a dose-finding study, aiming to determine the safe dosage of siplizumab. This study assesses how well participants tolerate the treatment and identifies potential side effects. As the trial is in an early stage, gathering more information is essential to fully understand the safety of siplizumab for individuals with type 1 diabetes. Researchers will closely monitor participants to ensure their safety during the study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Siplizumab is unique because it targets the CD2 receptor on T-cells, which plays a crucial role in the immune response that attacks insulin-producing cells in Type 1 Diabetes (T1D). Unlike standard treatments like insulin therapy, which manage blood sugar levels without addressing the underlying immune attack, Siplizumab offers a novel approach by potentially modifying the immune system's behavior. Researchers are excited about this treatment because it could not only improve blood sugar control but also preserve the body's ability to produce insulin, potentially reducing the long-term complications associated with T1D.

What evidence suggests that siplizumab might be an effective treatment for Type 1 diabetes?

Research shows that siplizumab might help people with Type 1 diabetes by improving the function of beta cells, which produce insulin. In earlier studies, siplizumab showed promise in protecting these cells in adults recently diagnosed with the condition. This protection is crucial because it helps the body continue producing insulin naturally. The treatment targets specific immune cells that mistakenly attack insulin-producing cells. Early findings suggest that siplizumab could slow the progression of Type 1 diabetes, offering hope for better disease management. Participants in this trial will receive different dosages of siplizumab to evaluate its effectiveness and safety across various groups. ^{1 2 3 6 7}

Who Is on the Research Team?

Stephen Gitelman, M.D.

Principal Investigator

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

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Siplizumab

Trial Overview The 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.

How Is the Trial Designed?

Group I: Children with T1D 0.22 mg/kg SQ dose Experimental Treatment 1 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 dose Experimental Treatment 1 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 dose Experimental Treatment 1 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 dose Experimental Treatment 1 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 dose Experimental Treatment 1 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 dose Experimental Treatment 1 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 dose Experimental Treatment 1 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 dose Experimental Treatment 1 Intervention

Cohort 1 Group1: 0.08 mg/kg SQ dose for a total of 12 weeks

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06025110

NCT06025110 | A Study of TCD601 (Siplizumab) in New ... The goal of this study is to determine if treatment with TCD601 improves beta-cell function in adults recently diagnosed with type 1 diabetes compared to ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05574335

Study Details | NCT05574335 | Siplizumab in T1DM 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.

3. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-effects-of-siplizumab-in-adults-with-new-onset-type-1-diabetes/

Study on the Effects of Siplizumab in Adults with New ... This study investigates the effects of siplizumab, an injectable medication, on insulin-producing cells in adults recently diagnosed with ...

4. ctv.veeva.com ctv.veeva.com/study/a-study-of-tcd601-siplizumab-in-new-onset-type-1-diabetes-patients

A Study of TCD601 (Siplizumab) in New Onset Type 1 ... The goal of this study is to determine if treatment with TCD601 improves beta-cell function in adults recently diagnosed with type 1 diabetes ...

5. trial.medpath.com trial.medpath.com/clinical-trial/55df84eb7543f545/ctis2023-506837-31-00-tcd601-siplizumab-type-1-diabetes

A 12-month, randomized, single-blind, placebo-controlled ... A 12-month, randomized, single-blind, placebo-controlled exposure-response study of TCD601 (siplizumab) in new onset type 1 diabetes patients (STRIDE).

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06025110?cond=diabetes

A Study of TCD601 (Siplizumab) in New Onset Type 1 ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the goal is to ...

7. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05574335

UCSF Diabetes Trial → Siplizumab in T1DM 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.