Siplizumab in T1DM (DESIGNATE)

A T Cell Phenotype Signature Driven Dose Finding Study With Siplizumab in Type 1 Diabetes Mellitus (ITN095AI)

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.

Study Overview

• Status: Terminated
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: Siplizumab

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado School of Medicine: Barbara Davis Center for Diabetes
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Children's Hospital: Department of Pediatrics, Pediatric Endocrinology and Diabetes
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center: Naomi Berrie Diabetes Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center: Department of Internal Medicine, Division of Endocrinology
  • Washington
    • Seattle, Washington, United States, 98101
      • Benaroya Research Institute at Virginia Mason: Diabetes Research Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 45 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Ability to provide informed consent (parental permission and informed assent of minor, if applicable).
2. Male or female between 8 to 45 years of age.
3. Diagnosis of T1DM within 18 months (550 days) of enrollment (V0).

4. Positive for at least one diabetes-related autoantibody, including:

   1. Glutamate decarboxylase (GAD-65),
   2. Insulin, if obtained within 10 days of the onset of exogenous insulin therapy,
   3. Insulinoma antigen-2 (IA-2), or
   4. Zinc transporter-8 (ZnT8).
5. Peak stimulated C-peptide level > 0.15 nmol/L following a MMTT conducted ≥ 21 days from diagnosis and within 37 days of enrollment (V0).
6. 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).

Exclusion Criteria:

1. 1. 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.
2. Severe reaction or anaphylaxis to humanized monoclonal antibodies.

3. Inability to complete a mixed meal tolerance test:

   1. History of significant allergy (e.g., anaphylaxis) to milk or soy proteins.
   2. Inability to disable hybrid closed loop system.

4. History of recent (within 180 days of V0) or ongoing uncontrolled bacterial, viral, fungal or other opportunistic infections, including:

   1. Human immunodeficiency virus (HIV),
   2. Current or prior infection with hepatitis B (HBV), as indicated by positive HBsAg or positive HBcAb,
   3. 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),
   4. 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,
   5. Active infection with EBV as detected by PCR or serology at the screening visit (V-1),
   6. Active infection with cytomegalovirus (CMV) as detected by PCR or serology at the screening visit (V-1),
5. Positive molecular testing of SARS-CoV-2 within 30 days of V-1.

6. Any of the following laboratory abnormalities confirmed by repeat tests at least 1 week apart:

   1. White blood count (WBC) < 3 x 103/μL;,
   2. CD 3+ CD4+, T cell count below the lower limit of normal,
   3. Platelet count < 150,000 /μL,
   4. Hemoglobin < 10 g/dL,
   5. ALT ≥ 2x upper limit of normal (ULN) or
   6. AST ≥ 2x ULN
   7. Serum creatinine >1.5x ULN in adults or >ULN in pediatrics.
   8. Absolute lymphocyte count (ALC) below the LLN.
7. Prior or current treatment that is known to alter the natural history of T1DM or immunologic status, including high dose inhaled, extensive topical or systemic glucocorticoids.
8. Current or prior (within last 14 days of the V-1 MMTT) use of any medication known to influence glucose tolerance (e.g., atypical antipsychotics, diphenylhydantoin, thiazide, or other potassium-depleting diuretics, β-adrenergic blockers, niacin).
9. Current or prior (within the last 30 days of the V-1 MMTT) use of non-insulin medications to treat insulin resistance or elevated glucose levels.
10. Previous or current diagnosis of malignancy.
11. History of bone marrow transplantation, solid organ transplantation, or primary immunodeficiencies.
12. History or diagnoses of other autoimmune diseases with the exception of stable thyroid or celiac disease.
13. History of significant cardiovascular disease.
14. Vaccination with a live attenuated vaccine (e.g., varicella, measles, mumps, rubella, cold-attenuated intranasal influenza vaccine, bacillus Calmette- Guérin, and smallpox) within 30 days of V0.
15. Women of child-bearing potential who are unwilling to use a medically acceptable form of contraception from 14 days prior to V0 until study Week 52.
16. Women who are pregnant, lactating, or planning on pregnancy during the study.
17. Current, diagnosed mental illness (e.g., severe depression), current diagnosed or self-reported drug, or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.
18. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adults with T1D 0.08 mg/kg SQ dose; Cohort 1 Group1: 0.08 mg/kg SQ dose for a total of 12 weeks	Drug: Siplizumab; Weekly siplizumab doses for a total of 12 weeks; Other Names: TCD 601
Experimental: Adults with T1D 0.12 mg/kg SQ dose; Cohort 1 Group 2: 0.12 mg/kg SQ dose for a total of 12 weeks	Drug: Siplizumab; Weekly siplizumab doses for a total of 12 weeks; Other Names: TCD 601
Experimental: Adults with T1D 0.18 mg/kg SQ dose; Cohort 1 Group 3:0.18 mg/kg SQ dose for a total of 12 weeks	Drug: Siplizumab; Weekly siplizumab doses for a total of 12 weeks; Other Names: TCD 601
Experimental: Adults with T1D 0.22 mg/kg SQ dose; Cohort 1 Group 4: 0.22 mg/kg SQ dose for a total of 12 weeks	Drug: Siplizumab; Weekly siplizumab doses for a total of 12 weeks; Other Names: TCD 601
Experimental: Children with T1D 0.08 mg/kg SQ dose; Cohort 2 Group 1:0.08 mg/kg SQ dose for a total of 12 weeks	Drug: Siplizumab; Weekly siplizumab doses for a total of 12 weeks; Other Names: TCD 601
Experimental: Children with T1D 0.12 mg/kg SQ dose; Cohort 2 Group 2:0.12 mg/kg SQ dose for a total of 12 weeks	Drug: Siplizumab; Weekly siplizumab doses for a total of 12 weeks; Other Names: TCD 601
Experimental: Children with T1D 0.18 mg/kg SQ dose; Cohort 2 Group 3: 0.18 mg/kg SQ dose for a total of 12 weeks	Drug: Siplizumab; Weekly siplizumab doses for a total of 12 weeks; Other Names: TCD 601
Experimental: Children with T1D 0.22 mg/kg SQ dose; Cohort 2 Group 4: 0.22 mg/kg SQ dose for a total of 12 weeks	Drug: Siplizumab; Weekly siplizumab doses for a total of 12 weeks; Other Names: TCD 601

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Adverse Events (AEs) in all siplizumab dosing arms	AE will include any untoward medical occurrence associated with siplizumab administration or any study-mandated procedure	From week 0 to week 52
Mixed Meal Tolerance Test (MMTT)-stimulated mean 2-hour C-peptide AUC	The mean 2-hour C-peptide AUC, measured in nmol/L, is computed by dividing the total AUC by 120 minutes	At Week 12, 24, 36, 52
Insulin use (U/kg/day)	Measured as U/kg body weight/day; participants should record the type and amount of insulin they have used during the 5-day period immediately preceding the beginning of treatment, middle of treatment, end of treatment, and at all follow-up visits	At Weeks 12, 24, 36 and 52.

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Stephen Gitelman, M.D., University of California San Francisco, School of Medicine: Diabetes Center

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2023
• Primary Completion (Actual): May 14, 2025
• Study Completion (Actual): October 20, 2025

Study Registration Dates

• First Submitted: September 19, 2022
• First Submitted That Met QC Criteria: October 6, 2022
• First Posted (Actual): October 10, 2022

Study Record Updates

• Last Update Posted (Actual): February 11, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Type 1 diabetes; T1DM; diabetic; siplizumab
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 1; siplizumab
• Other Study ID Numbers: DAIT ITN095AI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
• IPD Sharing Time Frame: On average, within 24 months after database lock for the trial.
• IPD Sharing Access Criteria: Open access.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No