Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a combined phase 1 and 2 study in 66 subjects, male or female, between 7-21 years of age that have recently (< 6 months) been diagnosed with type 1 diabetes. The first phase 1 part of the study includes six subjects openly receiving allogeneic Wharton's jelly derived mesenchymal stromal cells as the Advanced Therapy Medicinal Product (ATMP) Protrans, three each in the age ranges 7-11 and 12-18.The second part is a randomized, double-blinded placebo-controlled phase 2 study in parallel design comparing allogeneic Wharton's jelly derived mesenchymal stromal cells treatment (as Protrans) to placebo in children and adolescent subjects (7-21 years of age) diagnosed with type 1 diabetes, The primary objectives of this study will be to investigate the safety, tolerance and efficacy after an allogieneic infusion of Wharton's jelly derived mesenchymal stromal cells.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Wharton's jelly derived mesenchymal stromal cells (Protrans) | Active Comparator | Cells are dissolved in saline and given intravenously over a period of 20-40 min. 100 million cells to subjects < 50 kg and 200 million cells to subjects 50-100 kg (>100 kg is an exclusion criterion). |
|
| Placebo | Placebo Comparator | Placebo (saline) is given intravenously over a period of 20-40 min. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| the ATMP Protrans | Biological | Protrans consists of Wharton's jelly derived mesenchymal stromal cells |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety at one year evaluated as adverse events | Safety parameters will be evaluated at each study visit and recorded as adverse events. | One year |
| Safety at five years evaluated as adverse events | Safety parameters will be evaluated at each study visit and recorded as adverse events. | Five years |
| Efficacy measured as change in C-peptide Area under the curve to a mixed mealtolerance test. | Change in C-peptide Area under the curve (AUC) (0-120 min) for mixed meal tolerance test (MMTT) at 12 months following Protrans/Placebo infusion when compared to test performed before the start of treatment (baseline). | One year |
| Measure | Description | Time Frame |
|---|---|---|
| Insulin independency | The proportion of study participants independent of insulin at 6 months | One year |
| Insulin independency | The proportion of study participants independent of insulin at 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Gender differences | Differences in parameters of primary and secondary endpoints between genders | 6 months |
| Gender differences | Differences in parameters of primary and secondary endpoints between genders |
Inclusion Criteria:
Written informed consent for participation of the study (for subjects below 18 years of age also from both caregivers), given before undergoing any study-specific procedures
Clinical history compatible with type 1 diabetes diagnosed less than 6 months before enrolment
In the first part of the study, six subjects, three between 7-11 and three between 12-18 years of age (both groups inclusive at both ends), will be included. The sixty subjects in the second part of the study are stratified by age (12-21 and 7-11 years, respectively) and randomized to one of two treatment arms (active or placebo), with a 6-month safety delay for the younger stratum.
Mentally stable and, in the opinion of the investigator, able to comply with the procedures of the study protocol.
Fasting plasma C-peptide concentration >0.12 nmol/L.
Subjects of child-bearing potential must agree to using adequate contraception until one year after the administration of WJMSC/Placebo. Adequate contraception is as follows:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Per-Ola Carlsson, MD, PhD | Uppsala University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Uppsala University Hospital | Uppsala | 75185 | Sweden |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| One year |
| Low insulin needs | The proportion of study participants with daily insulin needs <0.25 U/kg at 6 months | 6 months |
| Low insulin needs | The proportion of study participants with daily insulin needs <0.25 U/kg at 12 months | 12 months |
| Insulin needs | Insulin requirement/kg body weigh at 6 months | 6 months |
| Insulin needs | Insulin requirement/kg body weigh at 12 months | 12 months |
| HbA1c | HbA1c at 6 months | 6 months |
| HbA1c | HbA1c at 12 months | 12 months |
| Time in target | Time in target (4-8 mmol/l) as measured by flash glucose monitoring for 14 days at 6 months | 6 months |
| Time in target | Time in target (4-8 mmol/l) as measured by flash glucose monitoring for 14 days at 12 months | 12 months |
| Time in range | Time in target (3.9-10 mmol/l) as measured by flash glucose monitoring for 14 days at 6 months | 6 months |
| Time in range | Time in target (3.9-10 mmol/l) as measured by flash glucose monitoring for 14 days at 12 months | 12 months |
| C-peptide | Change in C-peptide Area under the curve (AUC) (0-120 min) for mixed meal tolerance test (MMTT) at 6 months following Protrans/Placebo infusion when compared to test performed before the start of treatment (baseline). | 6 months |
| Change in peak C-peptide | Change in peak C-peptide concentration during the first 6 months | 6 months |
| Change in peak C-peptide | Change in peak C-peptide concentration during the first 12 months | 12 months |
| 12 months |
| HLA class 1 genotypes | Differences in parameters of primary and secondary endpoints between HLA class 1 genotypes | 6 months |
| HLA class 1 genotypes | Differences in parameters of primary and secondary endpoints between HLA class 1 genotypes | 12 months |
| age | Differences in parameters of primary and secondary endpoints between ages 7-11 and 12-21 | 6 months |
| age | Differences in parameters of primary and secondary endpoints between ages 7-11 and 12-21 | 12 months |
| Autoantibodies | Change of levels of diabetes-related autoantibodies when compared to test before the start of treatment (baseline) | 6 months |
| Autoantibodies | Change of levels of diabetes-related autoantibodies when compared to test before the start of treatment (baseline) | 12 months |
| Peripheral blood mononuclear cells | Change in reactivity and cytokine production of peripheral blood mononuclear cells when compared to test before the start of treatment (baseline) | 6 months |
| Peripheral blood mononuclear cells | Change in reactivity and cytokine production of peripheral blood mononuclear cells when compared to test before the start of treatment (baseline) | 12 months |