Clinical trial NCT06919354: A Study of GNTI-122 in Adults Recently Diagnosed With T1D
Official title: POLARIS: A Phase 1, Single Dose, Open-label Study of GNTI-122 in Adults With Recently Diagnosed Type 1 Diabetes (T1D)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Type 1 Diabetes (T1D)
Type 1 Diabetes Mellitus
Lead sponsor: GentiBio, Inc
Sponsor class: INDUSTRY
First posted: 2025-04-09
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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, an investigational cell therapy manufactured from a participant's own blood cells in adult participants with recently diagnosed T1D. After assessment of eligibility, participants who qualify for the study will be enrolled sequentially in 1 of 3 cohorts. Cohort 1 participants (n=3) receive a low dose of GNTI-122 . Cohort 2 participants (n=3) receive a high dose of GNTI-122. Cohort 3 participants (n=10) receive a high dose of GNTI-122 in combination with rapamycin. Participants are followed for 78 weeks after the administration of GNTI-122 during which safety and efficacy assessments are made, including vital signs, ECG, physical exam, clinical labs, and monitoring of adverse events and concomitant medications. 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. The study will include sentinel dosing and a Safety Review Committee to ensure participant safety.

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 120 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 28 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.

Eligibility criteria: Inclusion Criteria:

1. Male and female participants aged ≥18 to ≤45 years with recently diagnosed (within 120 days of Screening) T1D according to American Diabetes Association criteria.
2. Participant has residual β-cell function during Screening, defined as random C-peptide ≥ 0.2 nmol/L.
3. Positive for at least one T1D-associated autoantibody.
4. Able and willing to provide written, informed consent as approved by the IRB.
5. Requires and is on insulin therapy.
6. Is confirmed positive for the HLA-DRB1\*04:01 allele.
7. 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:

1. Type 2 diabetes.
2. Experienced DKA within 4 weeks prior to or during Screening.
3. Unwilling or unable to comply with study procedures or schedule.
4. Chronic or uncontrolled medical condition.
5. Has another active or autoimmune or inflammatory disease with the exception of well-controlled Hashimoto's thyroiditis, celiac disease, or vitiligo.
6. Participation in another clinical study or active follow-up in a prior study.

Primary outcomes:
measure: Safety and tolerability of GNTI-122 with and without rapamycin in adult participants with recently diagnosed T1D
timeFrame: Week 78
Secondary outcomes:
measure: Cellular kinetics of GNTI-122 with and without rapamycin in adult participants with recently diagnosed T1D
timeFrame: Week 78
measure: Cellular kinetics of GNTI-122 with and without rapamycin in adult participants with recently diagnosed T1D
timeFrame: Week 78
measure: Cellular kinetics of GNTI-122 with and without rapamycin in adult participants with recently diagnosed T1D
timeFrame: Week 78
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California - San Diego
state: California
city: San Francisco
country: United States
facility: University of California - San Francisco
state: California
city: Gainesville
country: United States
facility: University of Florida - Gainesville
state: Florida
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: New York City
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: GentiBio, Inc
name: Mark Bach, MD
role: STUDY_DIRECTOR
References: