Diabetes Mellitus, Type 1Phase 2NCT00806572
Treatment With hOKT3gamma1(Ala-Ala) in T1DM
A Phase 2 study testing hOKT3gamma1(Ala-Ala) in people with Diabetes Mellitus, Type 1, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 sites in United States.
Trial summary
This is a phase II study to examine the clinical and immunological effects of humanized FcR non-binding anti-CD3 mAb in participants with Type 1 diabetes mellitus (T1DM), and to develop this therapy to prevent the immune destruction leading to β cell loss. Read more about this study
- Who is it for?
- Ages 7 to 30 years
- Conditions the study is for
- Diabetes Mellitus, Type 1
- What is being tested?
- hOKT3gamma1(Ala-Ala)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 3 sitesUnited States
- Study dates
- May 2002to Aug 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 7 to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- diagnosed with T1DM within the past 6 weeks
- have a body weight ≥26 kg at the time of enrollment
- have detectable anti-GAD, anti-ICA512/IA-2, or insulin autoantibodies (if the participant has been on insulin ≤10 days).
Who cannot join
- Pregnant or lactating females;
- Prior OKT3 treatment;
- Known hypersensitivity to murine products;
- Uncompensated heart failure or fluid overload, recent myocardial infarction;
- History of epilepsy, cancer, active infection, atopic disease, active Grave's disease, cystic fibrosis, sickle cell anemia, neuropathy, peripheral vascular disease, cerebrovascular disease, any concurrent autoimmune diseases, asthma;
- Any medical condition that in the opinion of the investigator will interfere with safe completion of the trial;
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- Inability to give informed consent;
- Prior participation in a clinical trial that could potentially affect diabetes or immunologic status;
- Participation in a clinical trial within the last 6 weeks;
- HIV positive;
- Positive for Hepatitis B surface antigen or Anti-Hepatitis C antibody;
- Seropositivity for Toxoplasmosis (IgG);
- Lymphopenia (<1000 lymphocytes/microliter);
- Thrombocytopenia (<150,000/mm3 platelets);
- Anemia (Hgb < 10g/dL);
- Vaccination with a live virus within the past 6 weeks;
- Positive PPD skin test;
- Any infectious mononucleosis-like illness within the 3 months prior to enrollment;
- Serologic evidence of acute infection with EBV or CMV based on tests listed and as defined by the protocol.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Naomie Berrie Diabetes Center, Columbia University
New York, New York, 10032
University of California San Francisco
San Francisco, California, 94143
Benaroya Research Institute
Seattle, Washington, 98101
About this study
Official title: Phase II Multiple Dose Treatment of Type 1 Diabetes Mellitus With hOKT3gamma1(Ala-Ala)
This is a phase II study to examine the clinical and immunological effects of humanized FcR non-binding anti-CD3 mAb in participants with Type 1 diabetes mellitus (T1DM), and to develop this therapy to prevent the immune destruction leading to β cell loss.
Read the detailed description
This is a 2-arm, open-label phase II trial involving 0 or 3 cycles of treatment 6 months apart with hOKT3γ1 (Ala-Ala), over the first year of disease in participants with new onset T1DM. Each cycle consists of 12 daily doses of hOKT3γ1 (Ala-Ala).
Participants will be randomized in a ratio of 2:1 to either the experimental arm or the control arm and will be stratified by study site.
To be eligible, participants must be: male or female between 7-30 years of age, diagnosed with T1DM within the past 6 weeks, have a body weight ≥26 kg at the time of enrollment and have detectable anti-GAD, anti-ICA512/IA-2, or insulin autoantibodies (if the participant has been on insulin ≤10 days).
Participants randomized to the experimental group will start the first cycle of hOKT3γ1 (Ala-Ala) within 4-8 weeks of T1DM diagnosis. Each participant randomized to the experimental group will receive 3 cycles of drug treatment, separated by 6 months each. Each cycle consists of 12 days of drug treatment.
Both groups will undergo the Mixed Meal Stimulated C-Peptide Test and receive blood draws for mechanistic studies on the same schedule.
- Conditions
- Diabetes Mellitus, Type 1
- Being tested
- hOKT3gamma1(Ala-Ala)
- Keywords
- Diabetes, juvenile diabetes, teplizumab
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
hOKT3gamma1(Ala-Ala)Drug
Also called teplizumab
3 cycles, six months apart, each consisting of 12 daily infusions with 455-1818ug/m2 hOKT3g1(Ala-Ala)
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Not described Receives: Drug: hOKT3gamma1(Ala-Ala) |
| Control | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
4-hour C-peptide AUC
Measured: 24 months
Secondary outcomes (1)
Insulin usage
Measured: throughout study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2008 (estimated)
- Study startMay 2002
- Primary completionJul 2004
- Study completionAug 2007
Why it stopped: Adverse events related to drug lot
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 1Studies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN)
- Responsible party
- Sponsor
- Investigators
- Kevan C Herold, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00806572
- Sponsor's protocol ID
- DAIT ITN007AI
- Other IDs
- NDB01
- Status last verified
- Feb 2017
- First submitted
- 9 Dec 2008
- Last updated
- 8 Feb 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Data access is provided to the public in Participant level data and additional relevant materials are available to the public in : 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools available to researchers; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal that makes data from the consortium's clinical trials publicly available.
Publications
Herold KC, Gitelman S, Greenbaum C, Puck J, Hagopian W, Gottlieb P, Sayre P, Bianchine P, Wong E, Seyfert-Margolis V, Bourcier K, Bluestone JA; Immune Tolerance Network ITN007AI Study Group. Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb Teplizumab preserves insulin production for up to 5 years. Clin Immunol. 2009 Aug;132(2):166-73. doi: 10.1016/j.clim.2009.04.007. Epub 2009 May 14.
PubMed 19443276
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Multiple Dose Treatment of Type 1 Diabetes Mellitus With hOKT3gamma1(Ala-Ala)
- ClinicalTrials.gov ID
- NCT00806572
- Acronym / sponsor ID
- DAIT ITN007AI
- Conditions
- Diabetes Mellitus, Type 1
- Keywords
- Diabetes, juvenile diabetes, teplizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Adverse events related to drug lot
- Enrolment
- 10 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Immune Tolerance Network (ITN)
- Study start
- May 2002
- Primary completion
- Jul 2004 (actual)
- Study completion
- Aug 2007 (actual)
- First posted
- 11 Dec 2008 (estimated)
- Results
- Not posted in the source record
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 phase II study to examine the clinical and immunological effects of humanized FcR non-binding anti-CD3 mAb in participants with Type 1 diabetes mellitus (T1DM), and to develop this therapy to prevent the immune destruction leading to β cell loss.
Detailed description
This is a 2-arm, open-label phase II trial involving 0 or 3 cycles of treatment 6 months apart with hOKT3γ1 (Ala-Ala), over the first year of disease in participants with new onset T1DM. Each cycle consists of 12 daily doses of hOKT3γ1 (Ala-Ala).
Participants will be randomized in a ratio of 2:1 to either the experimental arm or the control arm and will be stratified by study site.
To be eligible, participants must be: male or female between 7-30 years of age, diagnosed with T1DM within the past 6 weeks, have a body weight ≥26 kg at the time of enrollment and have detectable anti-GAD, anti-ICA512/IA-2, or insulin autoantibodies (if the participant has been on insulin ≤10 days).
Participants randomized to the experimental group will start the first cycle of hOKT3γ1 (Ala-Ala) within 4-8 weeks of T1DM diagnosis. Each participant randomized to the experimental group will receive 3 cycles of drug treatment, separated by 6 months each. Each cycle consists of 12 days of drug treatment.
Both groups will undergo the Mixed Meal Stimulated C-Peptide Test and receive blood draws for mechanistic studies on the same schedule.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: hOKT3gamma1(Ala-Ala) |
| Control | No intervention | – |
Who may qualify
- Ages
- 7 to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (3 listed)
- diagnosed with T1DM within the past 6 weeks
- have a body weight ≥26 kg at the time of enrollment
- have detectable anti-GAD, anti-ICA512/IA-2, or insulin autoantibodies (if the participant has been on insulin ≤10 days).
Key exclusion criteria (19 listed)
- Pregnant or lactating females;
- Prior OKT3 treatment;
- Known hypersensitivity to murine products;
- Uncompensated heart failure or fluid overload, recent myocardial infarction;
- History of epilepsy, cancer, active infection, atopic disease, active Grave's disease, cystic fibrosis, sickle cell anemia, neuropathy, peripheral vascular disease, cerebrovascular disease, any concurrent autoimmune diseases, asthma;
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 |
|---|---|---|
| hOKT3gamma1(Ala-Ala)Also: teplizumab3 cycles, six months apart, each consisting of 12 daily infusions with 455-1818ug/m2 hOKT3g1(Ala-Ala) | Drug | Treatment |
Primary outcome
4-hour C-peptide AUC
Time frame: 24 months
1 secondary outcome
Insulin usage
Time frame: throughout study
Results and safety
The study was stopped early (reason given: Adverse events related to drug lot). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2017.
- Results publication: PubMed 19443276Herold KC, Gitelman S, Greenbaum C, Puck J, Hagopian W, Gottlieb P, Sayre P, Bianchine P, Wong E, Seyfert-Margolis V, Bourcier K, Bluestone JA; Immune Tolerance Network ITN007AI Study Group. Treatment of patients with new onset Type 1 diabetes with a single course of anti-CD3 mAb Teplizumab preserves insulin production for up to 5 years. Clin Immunol. 2009 Aug;132(2):166-73. doi: 10.1016/j.clim.2009.04.007. Epub 2009 May 14.
- National Institute of Allergy and Infectious Diseases (NIAID) websiteLink provided by the sponsor.
- Division of Allergy, Immunology, and Transplantation (DAIT) websiteLink provided by the sponsor.
- Immune Tolerance Network (ITN) websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Data access is provided to the public in Participant level data and additional relevant materials are available to the public in : 1.) the Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools available to researchers; and 2.) TrialShare, the Immune Tolerance Network (ITN) Clinical Trials Research Portal that makes data from the consortium's clinical trials publicly available.
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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.
Kevan C Herold, MD principal investigator
Yale University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing hOKT3gamma1(Ala-Ala) in people with Diabetes Mellitus, Type 1, run by National Institute of Allergy and Infectious Diseases (NIAID) at 3 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 3 inclusion and 19 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 8 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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 phase mean?
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?
The study was stopped early (reason given: Adverse events related to drug lot). Results are not available in the source record.
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?
4-hour C-peptide AUC (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00806572, which also lists 1 linked publication.
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 8 Feb 2017.