Siplizumab in T1DM

NCT05574335 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: DAIT ITN095AI
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 5

Brief Summary

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. 1.Assess the safety profile of siplizumab in recently diagnosed T1DM.
2. 2.Assess the effects of siplizumab on residual beta cell function in recently diagnosed T1DM participants.

Conditions

Type 1 Diabetes Mellitus

Keywords

diabetic; Type 1 diabetes; T1DM; siplizumab

Outcome Measures

Primary Outcomes (1)

• Number of Participants with a T cell phenotype signature response

  Evaluating four siplizumab dosing regimens for induction of a T cell phenotype signature is based on a 20% increase or greater from baseline in PD1+TIGIT+ frequency within circulating CD4 Tem and a 75% increase or greater from baseline in the CD4 Treg/Tem ratio in blood. The two criteria will be evaluated at weeks 2, 4, 8, and 12. An individual who achieves both signature criteria at any time point on or before week 12 is counted as having the signature response. Both criteria do not need to be achieved at the same time point.

  From week 0 (baseline) to week 12

Secondary Outcomes (3)

• Frequency of Adverse Events (AEs) in all siplizumab dosing arms

  From week 0 to week 52

• Mixed Meal Tolerance Test (MMTT)-stimulated mean 2-hour C-peptide AUC

  At Week 12, 24, 36, 52

• Insulin use (U/kg/day)

  At Weeks 12, 24, 36 and 52.

Study Arms (8)

Adults with T1D 0.08 mg/kg SQ dose

EXPERIMENTAL

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

Drug: Siplizumab

Adults with T1D 0.12 mg/kg SQ dose

EXPERIMENTAL

Cohort 1 Group 2: 0.12 mg/kg SQ dose for a total of 12 weeks

Drug: Siplizumab

Adults with T1D 0.18 mg/kg SQ dose

EXPERIMENTAL

Cohort 1 Group 3:0.18 mg/kg SQ dose for a total of 12 weeks

Drug: Siplizumab

Adults with T1D 0.22 mg/kg SQ dose

EXPERIMENTAL

Cohort 1 Group 4: 0.22 mg/kg SQ dose for a total of 12 weeks

Drug: Siplizumab

Children with T1D 0.08 mg/kg SQ dose

EXPERIMENTAL

Cohort 2 Group 1:0.08 mg/kg SQ dose for a total of 12 weeks

Drug: Siplizumab

Children with T1D 0.12 mg/kg SQ dose

EXPERIMENTAL

Cohort 2 Group 2:0.12 mg/kg SQ dose for a total of 12 weeks

Drug: Siplizumab

Children with T1D 0.18 mg/kg SQ dose

EXPERIMENTAL

Cohort 2 Group 3: 0.18 mg/kg SQ dose for a total of 12 weeks

Drug: Siplizumab

Children with T1D 0.22 mg/kg SQ dose

EXPERIMENTAL

Cohort 2 Group 4: 0.22 mg/kg SQ dose for a total of 12 weeks

Drug: Siplizumab

Interventions

Siplizumab DRUG

Weekly siplizumab doses for a total of 12 weeks

Also known as: TCD 601

Adults with T1D 0.08 mg/kg SQ dose; Adults with T1D 0.12 mg/kg SQ dose; Adults with T1D 0.18 mg/kg SQ dose; Adults with T1D 0.22 mg/kg SQ dose; Children with T1D 0.08 mg/kg SQ dose; Children with T1D 0.12 mg/kg SQ dose; Children with T1D 0.18 mg/kg SQ dose; Children with T1D 0.22 mg/kg SQ dose

Eligibility Criteria

• Age: 8 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Ability to provide informed consent (parental permission and informed assent of minor, if applicable).
• Male or female between 8 to 45 years of age.
• Diagnosis of T1DM within 18 months (550 days) of enrollment (V0).
• Positive for at least one diabetes-related autoantibody, including:
• Glutamate decarboxylase (GAD-65),
• Insulin, if obtained within 10 days of the onset of exogenous insulin therapy,
• Insulinoma antigen-2 (IA-2), or
• Zinc transporter-8 (ZnT8).
• Peak stimulated C-peptide level \> 0.15 nmol/L following a MMTT conducted ≥ 21 days from diagnosis and within 37 days of enrollment (V0).
• Completion of a SARS-CoV-2 vaccination, according to current CDC recommendations and FDA approval(s) or emergency use authorization(s). If the participant requires administration of vaccine(s) to meet eligibility requirements, they must complete the vaccination series at least 2 weeks prior to enrollment (V0).

You may not qualify if:

• \. Use of investigational drugs within 24 weeks of participation with the exception of any vaccine for the prevention of SARS-CoV-2 infection and emergency use authorization medications for treating SARS-CoV-2.
• Severe reaction or anaphylaxis to humanized monoclonal antibodies.
• Inability to complete a mixed meal tolerance test:
• History of significant allergy (e.g., anaphylaxis) to milk or soy proteins.
• Inability to disable hybrid closed loop system.
• History of recent (within 180 days of V0) or ongoing uncontrolled bacterial, viral, fungal or other opportunistic infections, including:
• Human immunodeficiency virus (HIV),
• Current or prior infection with hepatitis B (HBV), as indicated by positive HBsAg or positive HBcAb,
• Current or prior hepatitis C (HCV), unless treated with anti-viral therapy with achievement of a sustained virologic response (undetectable viral load 12 weeks after cessation of therapy),
• Positive QuantiFERON-TB Gold or QuantiFERON-TB Gold Plus tests. PPD or T-SPOT®.TB may be substituted for the QuantiFERON-TB Gold or QuantiFERON-TB Gold Plus tests,
• Active infection with EBV as detected by PCR or serology at the screening visit (V-1),
• Active infection with cytomegalovirus (CMV) as detected by PCR or serology at the screening visit (V-1),
• Positive molecular testing of SARS-CoV-2 within 30 days of V-1.
• Any of the following laboratory abnormalities confirmed by repeat tests at least 1 week apart:
• White blood count (WBC) \< 3 x 103/μL;,

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (5)

University of Colorado School of Medicine: Barbara Davis Center for Diabetes

Aurora, Colorado, 80045, United States

Location

University of Iowa Children's Hospital: Department of Pediatrics, Pediatric Endocrinology and Diabetes

Iowa City, Iowa, 52242, United States

Location

Columbia University Medical Center: Naomi Berrie Diabetes Center

New York, New York, 10032, United States

Location

University of Texas Southwestern Medical Center: Department of Internal Medicine, Division of Endocrinology

Dallas, Texas, 75390, United States

Location

Benaroya Research Institute at Virginia Mason: Diabetes Research Program

Seattle, Washington, 98101, United States

Location

Related Links

• Immune Tolerance Network (ITN)
• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

siplizumab

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Stephen Gitelman, M.D.

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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2022
• First Posted: October 10, 2022
• Study Start: April 26, 2023
• Primary Completion: May 14, 2025
• Study Completion: October 20, 2025
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: On average, within 24 months after database lock for the trial.
• Access Criteria: Open access.

Locations

US (5)