Type 1 Diabetes MellitusPhase 1/2DESIGNATENCT05574335
Siplizumab in T1DM
A Phase 1/2 study testing Siplizumab in people with Type 1 Diabetes Mellitus, run by National Institute of Allergy and Infectious Diseases (NIAID) at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 8 to 45 years
- Conditions the study is for
- Type 1 Diabetes Mellitus
- What is being tested?
- Siplizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 5 sitesUnited States
- Study dates
- 18 May 2023to 20 Oct 2025
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 45 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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,
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- 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).
Who cannot join
- 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.
- 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:
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- 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;,
- CD 3+ CD4+, T cell count below the lower limit of normal,
- Platelet count < 150,000 /μL,
- Hemoglobin < 10 g/dL,
- ALT ≥ 2x upper limit of normal (ULN) or
- AST ≥ 2x ULN
- Serum creatinine >1.5x ULN in adults or >ULN in pediatrics.
- Absolute lymphocyte count (ALC) below the LLN.
- 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.
- 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).
- 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.
- Previous or current diagnosis of malignancy.
- History of bone marrow transplantation, solid organ transplantation, or primary immunodeficiencies.
- History or diagnoses of other autoimmune diseases with the exception of stable thyroid or celiac disease.
- History of significant cardiovascular disease.
- 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.
- 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.
- Women who are pregnant, lactating, or planning on pregnancy during the study.
- 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.
- 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.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Colorado School of Medicine: Barbara Davis Center for Diabetes
Aurora, Colorado, 80045
University of Texas Southwestern Medical Center: Department of Internal Medicine, Division of Endocrinology
Dallas, Texas, 75390
University of Iowa Children's Hospital: Department of Pediatrics, Pediatric Endocrinology and Diabetes
Iowa City, Iowa, 52242
Columbia University Medical Center: Naomi Berrie Diabetes Center
New York, New York, 10032
Benaroya Research Institute at Virginia Mason: Diabetes Research Program
Seattle, Washington, 98101
About this study
Official title: 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.
Read more
The secondary objectives are to:
- Assess the safety profile of siplizumab in recently diagnosed T1DM.
- Assess the effects of siplizumab on residual beta cell function in recently diagnosed T1DM participants.
- Conditions
- Type 1 Diabetes Mellitus
- Being tested
- Siplizumab
- Keywords
- diabetic, Type 1 diabetes, T1DM, siplizumab
- Medical subject headings
- Diabetes Mellitus, Type 1
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SiplizumabDrug
Also called TCD 601
Weekly siplizumab doses for a total of 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: Drug: Siplizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a T Cell Phenotype Signature Response
A participant is defined as achieving a T Cell phenotype signature response if the participant experiences both a 75% increase or greater from baseline in the CD4 Treg/Tem ratio in blood and a 20% increase or greater from baseline in PD1+TIGIT+ frequency within circulating CD4 Tem. The two criteria will be evaluated at weeks 2, 4, 8, and 12. Both criteria do not need to be achieved at the same time point.
Measured: Week 0 to Week 12
Secondary outcomes (3)
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
Measured: 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
Measured: 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
Measured: At Weeks 12, 24, 36 and 52.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2022
- Study start18 May 2023
- Primary completion14 May 2025
- Study completion20 Oct 2025
Why it stopped: Prior to termination the DESIGNATE study was an on enrollment hold due to greater than anticipated lymphodepletion. The pharmaceutical partner decided not to reopen its own T1D trial and ceased development of siplizumab in autoimmunity.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Stephen Gitelman, M.D., Study chair, University of California San Francisco, School of Medicine: Diabetes Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05574335
- Sponsor's protocol ID
- DAIT ITN095AI
- Acronym
- DESIGNATE
- Status last verified
- Jun 2026
- First submitted
- 19 Sep 2022
- Last updated
- 28 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.