Mesenchymal Stromal Cells to Treat Type 1 Diabetes in Children and Adolescents
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Active Comparator: Wharton's jelly derived mesenchymal stromal cells (Protrans) 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). |
Biological: the ATMP Protrans
Protrans consists of Wharton's jelly derived mesenchymal stromal cells
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Placebo Comparator: Placebo Placebo (saline) is given intravenously over a period of 20-40 min. |
Biological: the ATMP Protrans
Protrans consists of Wharton's jelly derived mesenchymal stromal cells
|
Outcome Measures
Primary Outcome Measures
- Safety at one year evaluated as adverse events [One year]
Safety parameters will be evaluated at each study visit and recorded as adverse events.
- Safety at five years evaluated as adverse events [Five years]
Safety parameters will be evaluated at each study visit and recorded as adverse events.
- Efficacy measured as change in C-peptide Area under the curve to a mixed mealtolerance test. [One year]
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).
Secondary Outcome Measures
- Insulin independency [One year]
The proportion of study participants independent of insulin at 6 months
- Insulin independency [One year]
The proportion of study participants independent of insulin at 12 months
- Low insulin needs [6 months]
The proportion of study participants with daily insulin needs <0.25 U/kg at 6 months
- Low insulin needs [12 months]
The proportion of study participants with daily insulin needs <0.25 U/kg at 12 months
- Insulin needs [6 months]
Insulin requirement/kg body weigh at 6 months
- Insulin needs [12 months]
Insulin requirement/kg body weigh at 12 months
- HbA1c [6 months]
HbA1c at 6 months
- HbA1c [12 months]
HbA1c at 12 months
- Time in target [6 months]
Time in target (4-8 mmol/l) as measured by flash glucose monitoring for 14 days at 6 months
- Time in target [12 months]
Time in target (4-8 mmol/l) as measured by flash glucose monitoring for 14 days at 12 months
- Time in range [6 months]
Time in target (3.9-10 mmol/l) as measured by flash glucose monitoring for 14 days at 6 months
- Time in range [12 months]
Time in target (3.9-10 mmol/l) as measured by flash glucose monitoring for 14 days at 12 months
- C-peptide [6 months]
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).
- Change in peak C-peptide [6 months]
Change in peak C-peptide concentration during the first 6 months
- Change in peak C-peptide [12 months]
Change in peak C-peptide concentration during the first 12 months
Other Outcome Measures
- Gender differences [6 months]
Differences in parameters of primary and secondary endpoints between genders
- Gender differences [12 months]
Differences in parameters of primary and secondary endpoints between genders
- HLA class 1 genotypes [6 months]
Differences in parameters of primary and secondary endpoints between HLA class 1 genotypes
- HLA class 1 genotypes [12 months]
Differences in parameters of primary and secondary endpoints between HLA class 1 genotypes
- age [6 months]
Differences in parameters of primary and secondary endpoints between ages 7-11 and 12-21
- age [12 months]
Differences in parameters of primary and secondary endpoints between ages 7-11 and 12-21
- Autoantibodies [6 months]
Change of levels of diabetes-related autoantibodies when compared to test before the start of treatment (baseline)
- Autoantibodies [12 months]
Change of levels of diabetes-related autoantibodies when compared to test before the start of treatment (baseline)
- Peripheral blood mononuclear cells [6 months]
Change in reactivity and cytokine production of peripheral blood mononuclear cells when compared to test before the start of treatment (baseline)
- Peripheral blood mononuclear cells [12 months]
Change in reactivity and cytokine production of peripheral blood mononuclear cells when compared to test before the start of treatment (baseline)
Eligibility Criteria
Criteria
Inclusion Criteria:
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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
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Clinical history compatible with type 1 diabetes diagnosed less than 6 months before enrolment
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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.
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Mentally stable and, in the opinion of the investigator, able to comply with the procedures of the study protocol.
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Fasting plasma C-peptide concentration >0.12 nmol/L.
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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:
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oral (except low-dose gestagen (lynestrenol and noretisteron), injectable or implanted hormonal contraceptives.
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intrauterine device
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intrauterine system (for example progestin-releasing coil)
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vasectomized male (with appropriate postvasectomy documentation of the absence of sperm in the ejaculate)
Exclusion Criteria:
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Subjects with body weight >100 kg
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Subjects with unstable cardiovascular status incl. NYHA class III/IV or symptoms of angina pectoris.
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Subjects with uncontrolled hypertension (≥160/105 mmHg).
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Subjects with active on-going infections.
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Subjects with latent or previous as well as on-going therapy against tuberculosis, or exposed to tuberculosis or has traveled in areas with a high risk of tuberculosis or mycosis within the last 3 months.
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Subjects with serological evidence of infection with HIV, Treponema pallidum, hepatitis B antigen (subjects with serology consistent with previous vaccination and a history of vaccination are acceptable), or hepatitis C.
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Subjects with any systemic immune suppressive treatment
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Subjects with a known demyelinating disease or with symptoms or physical examination findings consistent with possible demyelinating disease.
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Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test.
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Subjects with known, or previous, malignancy.
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Taking oral anti-diabetic therapies or any other concomitant medication which may interfere with glucose regulation other than insulin.
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Subjects with GFR <60 ml/min/1.73 m2 body surface.
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Subject with any condition or any circumstance that, in the opinion of the investigator, would make it unsafe to undergo treatment with MSC.
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Known hypersensitivity against any excipients, i.e., dimethyl sulfoxide (DMSO).
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Uppsala University Hospital | Uppsala | Sweden | 75185 |
Sponsors and Collaborators
- Uppsala University Hospital
Investigators
- Principal Investigator: Per-Ola Carlsson, MD, PhD, Uppsala University Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- WJMSC-P01