Type 1 Diabetes MellitusPhase 2NCT00378508

Anti-CD3 mAb Treatment of Recent Onset Type 1 Diabetes

A Phase 2 study testing mAb hOKT3gamma1(Ala-Ala), Teplizumab in people with Type 1 Diabetes Mellitus, run by Yale University at 4 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This is a randomized placebo controlled study to test whether a single 14 course of treatment with the anti-CD3 monoclonal antibody, hOKT3gamma1(Ala-Ala),Teplizumab will prevent the loss of insulin secretory capacity in individuals with Type 1 diabetes of 4 - 12 months duration since diagnosis. Read more about this study

Who is it for?: Ages 8 to 30 years
Conditions the study is for: Type 1 Diabetes Mellitus
What is being tested?: mAb hOKT3gamma1(Ala-Ala), Teplizumab
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 63 participants
Where: 4 sitesUnited States
Study dates: Sep 2006to Aug 2013
Phase: Phase 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 30 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

age 8 - 30,
duration of diabetes 4 - 12 months,
weight greater than 27.5 kg,
stimulated C-peptide >= 0.2 pmol/ml

Who cannot join

asthma,
history of hepatitis C, hepatitis B, HIV

Trial locations and contacts

4 sites in 1 country.

United States4 sites

Barbara Davis Diabetes Center
Aurora, Colorado, 80045
Yale University
New Haven, Connecticut, 06520
Children's Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania, 10194
University of California at San Francisco
San Francisco, California, 94143

Other trials in United States

About this study

Official title: Phase II Trial of hOKT3gamma1(Ala-Ala) Teplizumab for Treatment of Patients With Recent Onset Type 1 Diabetes

Read the detailed description

The study design is a double blind placebo controlled trial that will enroll subjects between the ages of 8 - 30 who have had the diagnosis of Type 1 diabetes made 4 - 12 months prior to enrollment. A single 14 course of treatment with mAb hOKT3gamma1(Ala-Ala), Teplizumab will be given. The primary endpoint is the C-peptide response to a mixed meal at 12 months. A total of 60 subjects will be enrolled (30 in the drug treatment and 30 in the placebo groups) at 4 study sites: Yale University,the University of California at San Francisco, Children's Hospital of Philadelphia, and the Barbara Davis Diabetes Center.

Conditions: Type 1 Diabetes Mellitus
Being tested: mAb hOKT3gamma1(Ala-Ala), Teplizumab, Placebo Arm
Keywords: immune therapy, autoimmunity, insulin secretion, diabetes mellitus
Medical subject headings: Diabetes Mellitus, Type 1, Autoimmune Diseases, Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

mAb hOKT3gamma1(Ala-Ala), TeplizumabDrug
Also called mAb hOKT3gamma1(Ala-Ala), MGA031, Teplizumab
This is a randomized, two-arm, double blind placebo controlled phase II trial in which 60 participants with recent-onset T1DM are randomized at a 1:1 ratio to receive Teplizumab or placebo over a 14 day treatment period. The course of Teplizumab comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2.
Placebo ArmDrug

Study groups in NCT00378508
Study group	Role	What they receive
1	Experimental	The course of Teplizumab comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period. Receives: Drug: mAb hOKT3gamma1(Ala-Ala), Teplizumab
2	Placebo comparator	Normal saline infusion Receives: Drug: Placebo Arm

What is being measured

The primary outcome is the main question the study is designed to answer.

C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months
C-peptide secretory response was calculated as ln[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1]
For presentation, the C-peptide data were converted to the AUC as pmol/ml. This is adjusted for baseline.
Measured: At month 12 post-treatment
C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline
C-peptide secretory response was calculated as ln[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1]
For presentation, the C-peptide data were converted to the AUC as pmol/ml. This baseline data was used to adjust for the C-peptide AUC primary endpoint measure at 12 months.
Measured: At Baseline (before treatment)

Secondary outcomes (4)

Hemoglobin A1c
Measured: At 12 months post-treatment
Average Insulin Use Over 12 Months
Measured: After 12 months post-treatment
Baseline Insulin Use
Measured: At baseline (before treatment)
Baseline Hemoglobin A1c
Measured: At baseline (before treatment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2006Aug 2013

First posted20 Sep 2006 (estimated)
Study startSep 2006
Primary completionAug 2011
Study completionAug 2013

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.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
More trials run by Yale UniversityThe 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: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 63 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00378508
Sponsor's protocol ID: Delay-Study 5
Other IDs: R01DK057846
Status last verified: Aug 2021
First submitted: 18 Sep 2006
Last updated: 13 Aug 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, Donaldson D, Gitelman SE, Harlan DM, Xu D, Zivin RA, Bluestone JA. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med. 2002 May 30;346(22):1692-8. doi: 10.1056/NEJMoa012864.
PubMed 12037148
Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan DM, Bluestone JA. A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes. 2005 Jun;54(6):1763-9. doi: 10.2337/diabetes.54.6.1763.
PubMed 15919798
Sherr JL, Ghazi T, Wurtz A, Rink L, Herold KC. Characterization of residual beta cell function in long-standing type 1 diabetes. Diabetes Metab Res Rev. 2014 Feb;30(2):154-62. doi: 10.1002/dmrr.2478.
PubMed 24115337
Lebastchi J, Deng S, Lebastchi AH, Beshar I, Gitelman S, Willi S, Gottlieb P, Akirav EM, Bluestone JA, Herold KC. Immune therapy and beta-cell death in type 1 diabetes. Diabetes. 2013 May;62(5):1676-80. doi: 10.2337/db12-1207. Epub 2013 Feb 19.
PubMed 23423576
Herold KC, Gitelman SE, Willi SM, Gottlieb PA, Waldron-Lynch F, Devine L, Sherr J, Rosenthal SM, Adi S, Jalaludin MY, Michels AW, Dziura J, Bluestone JA. Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial. Diabetologia. 2013 Feb;56(2):391-400. doi: 10.1007/s00125-012-2753-4. Epub 2012 Oct 21.
PubMed 23086558

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 13 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase II Trial of hOKT3gamma1(Ala-Ala) Teplizumab for Treatment of Patients With Recent Onset Type 1 Diabetes
ClinicalTrials.gov ID: NCT00378508
Acronym / sponsor ID: Delay-Study 5
Conditions: Type 1 Diabetes Mellitus
Keywords: immune therapy, autoimmunity, insulin secretion, diabetes mellitus
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 63 participants (actual)
Lead sponsor: Yale UniversityUniversity, hospital or other
Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Juvenile Diabetes Research Foundation
Study start: Sep 2006
Primary completion: Aug 2011 (actual)
Study completion: Aug 2013 (actual)
First posted: 20 Sep 2006 (estimated)
Results: Posted 31 Oct 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
1	Experimental	Drug: mAb hOKT3gamma1(Ala-Ala), TeplizumabThe course of Teplizumab comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2 over a 14 day treatment period.
2	Placebo comparator	Drug: Placebo ArmNormal saline infusion

Who may qualify

Ages: 8 to 30 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (4 listed)

age 8 - 30,
duration of diabetes 4 - 12 months,
weight greater than 27.5 kg,
stimulated C-peptide >= 0.2 pmol/ml

Key exclusion criteria (2 listed)

asthma,
history of hepatitis C, hepatitis B, HIV

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
mAb hOKT3gamma1(Ala-Ala), TeplizumabAlso: mAb hOKT3gamma1(Ala-Ala), MGA031, TeplizumabThis is a randomized, two-arm, double blind placebo controlled phase II trial in which 60 participants with recent-onset T1DM are randomized at a 1:1 ratio to receive Teplizumab or placebo over a 14 day treatment period. The course of Teplizumab comprises daily doses of 51 µg/m2, 103 µg/m2, 207 µg/m2, 413 µg/m2, and 10 of 826 µg/m2.	Drug	1
Placebo Arm	Drug	2

Primary outcome

C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months
Time frame: At month 12 post-treatment
C-peptide secretory response was calculated as ln[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1] For presentation, the C-peptide data were converted to the AUC as pmol/ml. This is adjusted for baseline.
C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline
Time frame: At Baseline (before treatment)
C-peptide secretory response was calculated as ln[(Area Under the Curve of the C-peptide from the 240 minute MMTT/240 +1] For presentation, the C-peptide data were converted to the AUC as pmol/ml. This baseline data was used to adjust for the C-peptide AUC primary endpoint measure at 12 months.

4 secondary outcomes

Hemoglobin A1c
Time frame: At 12 months post-treatment
Average Insulin Use Over 12 Months
Time frame: After 12 months post-treatment
Baseline Insulin Use
Time frame: At baseline (before treatment)
Baseline Hemoglobin A1c
Time frame: At baseline (before treatment)

Results and safety

Results posted to the registry on 31 Oct 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Saline Infusions (Placebo)	29	27
Teplizumab Infusion (Active)	34	31

Primary outcome: C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months

Time frame: At month 12 post-treatment. Least squares mean (95% Confidence Interval). Unit: pmol/ml

Measure	Teplizumab Infusions (Active) n = 31	Saline Infusions (Placebo) n = 27
Value	0.451 (0.4 to 0.505)	0.371 (0.319 to 0.424)

Population analysed: This endpoint was compared in the modified intent to treat population which included all subjects with at least one post-randomization mixed meal tolerance test (MMTT)

Primary outcome: C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at Baseline

Time frame: At Baseline (before treatment). Least squares mean (95% Confidence Interval). Unit: pmol/ml

Measure	Teplizumab Infusions (Active) n = 31	Saline Infusions (Placebo) n = 27
Value	0.593 (0.493 to 0.699)	0.554 (0.417 to 0.705)

Population analysed: This endpoint was compared in the modified intent to treat population which included all subjects with at least one post-randomization mixed meal tolerance test (MMTT)

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: The adverse event data was collected throughout the duration of the study which was approximately 6 years.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Saline Infusions (Placebo)	0 of 29 (0%)	29 of 29 (100%)	Not reported
Teplizumab Infusion (Active)	1 of 34 (2.9%)	25 of 34 (73.5%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 12037148Herold KC, Hagopian W, Auger JA, Poumian-Ruiz E, Taylor L, Donaldson D, Gitelman SE, Harlan DM, Xu D, Zivin RA, Bluestone JA. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med. 2002 May 30;346(22):1692-8. doi: 10.1056/NEJMoa012864.
Background: PubMed 15919798Herold KC, Gitelman SE, Masharani U, Hagopian W, Bisikirska B, Donaldson D, Rother K, Diamond B, Harlan DM, Bluestone JA. A single course of anti-CD3 monoclonal antibody hOKT3gamma1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes. 2005 Jun;54(6):1763-9. doi: 10.2337/diabetes.54.6.1763.
Derived from this study: PubMed 24115337Sherr JL, Ghazi T, Wurtz A, Rink L, Herold KC. Characterization of residual beta cell function in long-standing type 1 diabetes. Diabetes Metab Res Rev. 2014 Feb;30(2):154-62. doi: 10.1002/dmrr.2478.
Derived from this study: PubMed 23423576Lebastchi J, Deng S, Lebastchi AH, Beshar I, Gitelman S, Willi S, Gottlieb P, Akirav EM, Bluestone JA, Herold KC. Immune therapy and beta-cell death in type 1 diabetes. Diabetes. 2013 May;62(5):1676-80. doi: 10.2337/db12-1207. Epub 2013 Feb 19.
Derived from this study: PubMed 23086558Herold KC, Gitelman SE, Willi SM, Gottlieb PA, Waldron-Lynch F, Devine L, Sherr J, Rosenthal SM, Adi S, Jalaludin MY, Michels AW, Dziura J, Bluestone JA. Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial. Diabetologia. 2013 Feb;56(2):391-400. doi: 10.1007/s00125-012-2753-4. Epub 2012 Oct 21.

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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 principal investigator

Yale University

Jeffrey A Bluestone, PhD principal investigator

University of California at San Francisco

4 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 mAb hOKT3gamma1(Ala-Ala), Teplizumab in people with Type 1 Diabetes Mellitus, run by Yale University at 4 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 4 inclusion and 2 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: finished, as of the sponsor's last update on 13 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 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. Some participants in this study may receive a placebo. 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?

Yes. Results are posted in the registry (first posted 31 Oct 2012). 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?

C-peptide Area Under the Curve (AUC) Response to a Mixed Meal Tolerance Test (MMTT) at 12 Months (time frame: At month 12 post-treatment). The study lists 2 primary outcomes in all. 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 NCT00378508, which also lists 5 linked publications.

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 13 Aug 2021.