Diabetes Mellitus
Conditions
Keywords
T1DM, Type 1 Diabetes Mellitus, T regulatory cell, Immunotherapy, Cell therapy, T-Reg
Brief summary
This clinical trial will explore the safety and effect of autologous ex vivo expanded polyclonal regulatory T-cells on beta cell function in patients, aged 8 to 17, with recent onset T1DM. Other measures of diabetes severity and the autoimmune response underlying T1DM will also be explored. Eligible subjects will receive a single infusion of CLBS03 (high or low dose) or placebo.
Interventions
BIOLOGICALCLBS03 Low Dose
BIOLOGICALCLBS03 High Dose
BIOLOGICALPlacebo
Sponsors
Sanford Health
California Institute for Regenerative Medicine (CIRM)
Lisata Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
8 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male and females aged 8 to 17 years of age * Diagnosis of T1DM within 100 days of receipt of study drug * Positive for at least one islet cell autoantibody * Peak MMTT-stimulated C-peptide level \> 0.2 pmol/mL (at the screening visit) * Weight of ≥30 kg * Must agree to use a reliable and acceptable method of contraception for the duration of participation * Willing and medically acceptable to postpone live vaccine immunizations for one year after infusion * Written informed consent and written assent
Exclusion criteria
* Hemoglobin less than the lower limit of normal * Leukocytes \<3,000/μL; neutrophils \<1,500/μL; lymphocytes \<800/μL; platelets \<100,000/μL * Regulatory T-cells present in peripheral blood at \<20 cells per μL * Current or ongoing use of non-insulin pharmaceuticals (that may affect glycemic control) * Current or anticipated use of systemic corticosteroids or other immunomodulatory drugs * Recent serious bacterial, viral, fungal, or other opportunistic infections * History of malignancy or serious uncontrolled cardiovascular, nervous system, pulmonary, renal, or gastrointestinal disease * Serologic evidence of current or past viral infection: human immunodeficiency virus (HIV), Hepatitis B, Hepatitis C, and human T-lymphotropic virus (HTLV) 1/2 * Positive QuantiFERON® tuberculosis (TB) test, purified protein derivative (PPD) skin test, history of tuberculosis, or active TB infection * Active infection with Epstein-Barr Virus or Cytomegalovirus * Liver disease * Pregnant or breast-feeding * Vaccination with a live virus within 8 weeks of receipt of study drug * Vaccination with a killed virus within 2 weeks of receipt of study drug * Participation in an investigational drug study within 90 days prior to screening * Previously treated with a T-Reg based cell therapy * History of allergy to gentamicin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 52 | Week 52 | The area-under-curve of sequential C-peptide concentrations (AUC-Cpep) during the mixed-meal tolerance test (MMTT) is the gold-standard method to assess residual beta-cell (ie, insulin) secretion in type 1 diabetes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 104 | Week 104 | The area-under-curve of sequential C-peptide concentrations (AUC-Cpep) during the mixed-meal tolerance test (MMTT) is the gold-standard method to assess residual beta-cell (ie, insulin) secretion in type 1 diabetes. |
| Change in Hemoglobin A1c (HbA1c) | Week 104 | — |
| Change From Baseline in Mean Daily Dose of Insulin | Week 104 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CLBS03 Low Dose A single infusion of CLBS03 Low Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP (United States Pharmacopoeia) infusion solution.
CLBS03 Low Dose | 40 |
| CLBS03 High Dose A single infusion of CLBS03 High Dose, a cell product comprised of autologous, ex vivo expanded regulatory T-cells resuspended in sterile USP infusion solution.
CLBS03 High Dose | 24 |
| Placebo A single infusion of placebo, consisting of the infusion solution only
Placebo | 46 |
| Total | 110 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 2 |
Baseline characteristics
| Characteristic | CLBS03 Low Dose | CLBS03 High Dose | Placebo | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 40 Participants | 24 Participants | 46 Participants | 110 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 2 Participants | 2 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 22 Participants | 44 Participants | 100 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 36 Participants | 23 Participants | 42 Participants | 101 Participants |
| Region of Enrollment United States | 40 participants | 24 participants | 46 participants | 110 participants |
| Sex: Female, Male Female | 10 Participants | 5 Participants | 13 Participants | 28 Participants |
| Sex: Female, Male Male | 30 Participants | 19 Participants | 33 Participants | 82 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 24 | 0 / 46 |
| other Total, other adverse events | 38 / 40 | 24 / 24 | 46 / 46 |
| serious Total, serious adverse events | 4 / 40 | 2 / 24 | 3 / 46 |
Outcome results
Primary
Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 52
The area-under-curve of sequential C-peptide concentrations (AUC-Cpep) during the mixed-meal tolerance test (MMTT) is the gold-standard method to assess residual beta-cell (ie, insulin) secretion in type 1 diabetes.
Time frame: Week 52
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CLBS03 Low Dose | Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 52 | -0.2863 pmol*hr/mL | Standard Deviation 0.25988 |
| CLBS03 High Dose | Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 52 | -0.3895 pmol*hr/mL | Standard Deviation 0.31425 |
| Placebo | Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 52 | -0.2670 pmol*hr/mL | Standard Deviation 0.25745 |
Secondary
Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 104
The area-under-curve of sequential C-peptide concentrations (AUC-Cpep) during the mixed-meal tolerance test (MMTT) is the gold-standard method to assess residual beta-cell (ie, insulin) secretion in type 1 diabetes.
Time frame: Week 104
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CLBS03 Low Dose | Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 104 | -0.4492 pmol*hr/mL | Standard Deviation 0.33135 |
| CLBS03 High Dose | Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 104 | -0.5224 pmol*hr/mL | Standard Deviation 0.33903 |
| Placebo | Change From Baseline in 4-hour Mixed Meal Tolerance Test (MMTT)-Stimulated C-peptide Area Under the Curve (AUC) at Week 104 | -0.4412 pmol*hr/mL | Standard Deviation 0.28923 |
Secondary
Change From Baseline in Mean Daily Dose of Insulin
Time frame: Week 104
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CLBS03 Low Dose | Change From Baseline in Mean Daily Dose of Insulin | 0.3840 U/kg body weight | Standard Deviation 0.39727 |
| CLBS03 High Dose | Change From Baseline in Mean Daily Dose of Insulin | 0.4619 U/kg body weight | Standard Deviation 0.4022 |
| Placebo | Change From Baseline in Mean Daily Dose of Insulin | 0.2874 U/kg body weight | Standard Deviation 0.33602 |
Secondary
Change in Hemoglobin A1c (HbA1c)
Time frame: Week 104
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CLBS03 Low Dose | Change in Hemoglobin A1c (HbA1c) | 1.56 HbA1c % | Standard Deviation 1.66 |
| CLBS03 High Dose | Change in Hemoglobin A1c (HbA1c) | 1.05 HbA1c % | Standard Deviation 1.474 |
| Placebo | Change in Hemoglobin A1c (HbA1c) | 1.77 HbA1c % | Standard Deviation 2.162 |