A Study of GNTI-122 in Adults Recently Diagnosed With T1D (POLARIS)
POLARIS: A Phase 1, Single Dose, Open-label Study of GNTI-122 in Adults With Recently Diagnosed Type 1 Diabetes (T1D)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is a 78-week single arm, multi center, Phase 1 study to evaluate the safety, tolerability, cellular kinetics, and biomarker changes in C-peptide over time of GNTI-122 in adult participants with recently (within 180 days of Screening) diagnosed T1D. GNTI-122 is an investigational cell therapy manufactured from a participant's own blood cells and is intended to help correct an imbalance of certain types of cells found in patients with Type 1 Diabetes (T1D).
After assessment of eligibility, participants who qualify for the study will be enrolled sequentially in 1 of 3 cohorts. Cohorts 1 and 2 are safety run-in cohorts (n=3 participants per cohort) in which each participant receives a single dose of GNTI 122 alone; Cohort 1 receives a low dose 1 of GNTI-122 and Cohort 2 receives a high dose of GNTI-122. Cohort 3 includes 10 participants that will receive a single high dose of GNTI-122 in combination with rapamycin (with a target trough concentration [Ctrough] of 3 to 6 ng/mL), which may extend the survival of GNTI-122. Participants will remain at the clinical site for observation for at least 4 hours after administration of GNTI-122.
Safety and tolerability assessments over the 78-week study include: vital signs, 12-lead electrocardiograms, physical examinations, clinical laboratory evaluations, monitoring of adverse events and concomitant medications. Risks to participants will be minimized by the incorporation of sentinel dosing (i.e., at least 28 days of safety assessments between first and second participant and at least 14 days between the second and third participant in Cohorts 1 and 2, and at least 14 days between the first and second participant and the second and third participant in Cohort 3) and the evaluation of safety and tolerability by a Safety Review Committee with at least 14 days of safety assessments (i.e., laboratory values and adverse event reporting) after 3 participants are dosed in Cohort 1 and Cohort 2. Disease markers (e.g., MMTT-stimulated C-peptide, HbA1c) and pharmacodynamic activity (e.g., lymphocyte subsets and phenotypes, effector T cell responses to islet antigens ex vivo, T1D autoantibodies) will be monitored serially throughout the study.
In Cohort 3, rapamycin concentrations will be measured periodically to ensure levels are in the target range of Ctrough level between 3 and 6 ng/mL.
Per Health Authority guidelines (Food and Drug Administration) for gene therapy products or advanced medicinal products, all participants treated with GNTI-122 who complete or discontinue from this study must be monitored for specific toxicities for a total of 15 years (semi-annually or annually), irrespective of their response to GNTI-122. This will be addressed in a separate protocol of a long-term follow-up study of these participants.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Kristin M Neff
- Phone Number: 857-327-5483
- Email: clinical_ops@GentiBio.com
Study Locations
-
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California
-
Duarte, California, United States, 91010
- Recruiting
- City of Hope Medical Center
-
Principal Investigator:
- Fouad Kandeel, MD, PhD
-
Contact:
- Fouad Kandeel, MD, PhD
- Phone Number: 866-444-7538
- Email: islets@coh.org
-
San Diego, California, United States, 92093-0990
- Recruiting
- University of California - San Diego
-
Principal Investigator:
- Jeremy Pettus, MD
-
Contact:
- Mateo Santizo
- Phone Number: 858-249-4020
- Email: alphastemcellclinic@health.ucsd.edu
-
Contact:
- Miguel Alvendia
-
San Francisco, California, United States, 94158
- Recruiting
- University of California - San Francisco
-
Principal Investigator:
- Stephen Gitelman, MD
-
Contact:
- Rebecca Wesch (Recruitment Coordinator)
- Phone Number: 844-813-8273
- Email: clinicalresearch@diabetes.ucsf.edu
-
-
Florida
-
Gainesville, Florida, United States, 32610
- Recruiting
- University of Florida - Gainesville
-
Principal Investigator:
- Brittany Bruggeman, MD
-
Contact:
- Jennifer Hosford
- Phone Number: 352-294-5759
- Email: jennifer.hosford@peds.ufl.edu
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Miami, Florida, United States, 33136
- Recruiting
- University of Miami, Diabetes Research Institute
-
Principal Investigator:
- David Baidal, MD
-
Contact:
- Carlos Blaschke, MD
- Phone Number: 305-243-4485
- Email: cblaschke@miami.edu
-
Contact:
- Julia Oliveira
- Phone Number: 305-243-3466
- Email: jmd636@med.miami.edu
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Massachusetts
-
Boston, Massachusetts, United States, 02215
- Recruiting
- Joslin Diabetes Center
-
Principal Investigator:
- Jason Gaglia, MD, MMSc
-
Contact:
- Michelle Zhang, Study Coordinator
- Phone Number: 888-813-8669
- Email: T1DTrials@joslin.harvard.edu
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-
New York
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New York, New York, United States, 10029
- Recruiting
- Icahn School of Medicine at Mount Sinai
-
Principal Investigator:
- Carol Levy, MD
-
Contact:
- Carol Levy, MD
- Phone Number: 212-241-0068
- Email: carol.levy@mssm.edu
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Contact:
- Camilla Levister, NP
- Phone Number: 212-241-5177
- Email: Camilla.levister@mssm.edu
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New York, New York, United States, 10032
- Not yet recruiting
- Columbia University
-
Principal Investigator:
- Jacqueline Lonier, MD
-
Contact:
- Amy Doytchinov
- Phone Number: 646-581-2532
- Email: berrietrials@cumc.columbia.edu
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North Carolina
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Chapel Hill, North Carolina, United States, 27514
- Recruiting
- University of North Carolina at Chapel Hill
-
Principal Investigator:
- John Buse, MD
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Contact:
- Rachael Unger
- Phone Number: 984-974-3004
- Email: uncdiabetes@med.unc.edu
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Durham, North Carolina, United States, 27710
- Recruiting
- Duke University
-
Contact:
- Megan Reaves
- Phone Number: 919-660-2272
- Email: megan.reaves@duke.edu
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Principal Investigator:
- Jennifer Green, MD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Male and female participants aged ≥18 to ≤55 years with recently diagnosed (within 180 days of Screening) T1D according to American Diabetes Association criteria.
- Participant has residual β-cell function during Screening, defined as random C-peptide ≥ 0.2 nmol/L.
- Positive for at least one T1D-associated autoantibody.
- Able and willing to provide written, informed consent as approved by the IRB.
- Is confirmed positive for the HLA-DRB1*04:01 allele.
- Has adequate vascular access to undergo leukapheresis with no known contraindications.
8. Female participants of childbearing potential must have a negative serum pregnancy test at Screening, must be not lactating, and must agree to protocol-specified contraception.
9. Male participants of childbearing potential must agree to protocol specified contraception.
10. Other than T1D, participant is in good general health.
Exclusion Criteria:
- Type 2 diabetes.
- Experienced DKA within 4 weeks prior to or during Screening.
- Unwilling or unable to comply with study procedures or schedule.
- Chronic or uncontrolled medical condition.
- Has another active or autoimmune or inflammatory disease with the exception of well-controlled Hashimoto's thyroiditis, celiac disease, or vitiligo.
- Participation in another clinical study or active follow-up in a prior study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: GNTI-122
|
GNTI-122 is an investigational cell therapy manufactured from a participant's own blood cells and is intended to help correct an imbalance of certain types of cells found in participants with Type 1 Diabetes.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Safety and tolerability of GNTI-122 with and without rapamycin in adult participants with recently diagnosed T1D
Time Frame: Week 78
|
Cumulative AEs/SAEs and clinically significant abnormalities in physical exams, vital signs, clinical laboratory measures, and other clinical assessments
|
Week 78
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Cellular kinetics of GNTI-122 with and without rapamycin in adult participants with recently diagnosed T1D
Time Frame: Week 78
|
Measurement of maximum concentration of circulating engineered regulatory T cells as measured by droplet digital polymerase chain reaction
|
Week 78
|
|
Cellular kinetics of GNTI-122 with and without rapamycin in adult participants with recently diagnosed T1D
Time Frame: Week 78
|
Measurement of area under the concentration-time curve [AUC] of circulating engineered regulatory T cells
|
Week 78
|
|
Cellular kinetics of GNTI-122 with and without rapamycin in adult participants with recently diagnosed T1D
Time Frame: Week 78
|
Measurement of half-life of circulating engineered regulatory T cells
|
Week 78
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Mark Bach, MD, GentiBio, Inc
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- GNTI-122-T1D-1001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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