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
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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,
Show all 10Show fewer
- 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:
Show all 34Show fewer
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A T Cell Phenotype Signature Driven Dose Finding Study With Siplizumab in Type 1 Diabetes Mellitus (ITN095AI)
- ClinicalTrials.gov ID
- NCT05574335
- Acronym / sponsor ID
- DESIGNATE / DAIT ITN095AI
- Conditions
- Type 1 Diabetes Mellitus
- Keywords
- diabetic, Type 1 diabetes, T1DM, siplizumab
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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.
- Enrolment
- 8 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 18 May 2023 (actual)
- Primary completion
- 14 May 2025 (actual)
- Study completion
- 20 Oct 2025 (actual)
- First posted
- 10 Oct 2022 (actual)
- Results
- Posted 28 Jul 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Adults with T1D 0.08 mg/kg SQ dose | Experimental | Drug: SiplizumabCohort 1 Group1: 0.08 mg/kg SQ dose for a total of 12 weeks |
| Adults with T1D 0.12 mg/kg SQ dose | Experimental | Drug: SiplizumabCohort 1 Group 2: 0.12 mg/kg SQ dose for a total of 12 weeks |
| Adults with T1D 0.18 mg/kg SQ dose | Experimental | Drug: SiplizumabCohort 1 Group 3:0.18 mg/kg SQ dose for a total of 12 weeks |
| Adults with T1D 0.22 mg/kg SQ dose | Experimental | Drug: SiplizumabCohort 1 Group 4: 0.22 mg/kg SQ dose for a total of 12 weeks |
| Children with T1D 0.08 mg/kg SQ dose | Experimental | Drug: SiplizumabCohort 2 Group 1:0.08 mg/kg SQ dose for a total of 12 weeks |
| Children with T1D 0.12 mg/kg SQ dose | Experimental | Drug: SiplizumabCohort 2 Group 2:0.12 mg/kg SQ dose for a total of 12 weeks |
| Children with T1D 0.18 mg/kg SQ dose | Experimental | Drug: SiplizumabCohort 2 Group 3: 0.18 mg/kg SQ dose for a total of 12 weeks |
| Children with T1D 0.22 mg/kg SQ dose | Experimental | Drug: SiplizumabCohort 2 Group 4: 0.22 mg/kg SQ dose for a total of 12 weeks |
Who may qualify
- Ages
- 8 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (10 listed)
- 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:
- Peak stimulated C-peptide level > 0.15 nmol/L following a MMTT conducted ≥ 21 days from diagnosis and within 37 days of enrollment (V0).
Key exclusion criteria (34 listed)
- 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 recent (within 180 days of V0) or ongoing uncontrolled bacterial, viral, fungal or other opportunistic infections, including:
- Positive molecular testing of SARS-CoV-2 within 30 days of V-1.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SiplizumabAlso: TCD 601Weekly siplizumab doses for a total of 12 weeks | Drug | 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 |
Primary outcome
Number of Participants With a T Cell Phenotype Signature Response
Time frame: Week 0 to Week 12
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.
3 secondary outcomes
Frequency of Adverse Events (AEs) in All Siplizumab Dosing Arms
Time frame: From week 0 to week 52
Mixed Meal Tolerance Test (MMTT)-Stimulated Mean 2-hour C-peptide AUC
Time frame: At Week 12, 24, 36, 52
Insulin Use (U/kg/Day)
Time frame: At Weeks 12, 24, 36 and 52.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Immune Tolerance Network (ITN)Link provided by the sponsor.
- National Institute of Allergy and Infectious Diseases (NIAID)Link provided by the sponsor.
- Division of Allergy, Immunology, and Transplantation (DAIT)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen Gitelman, M.D. study chair
University of California San Francisco, School of Medicine: Diabetes Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With a T Cell Phenotype Signature Response (time frame: Week 0 to Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2026.