Type I diabetes MedDRA version: 21.1 Level: PT Classification code 10067584 Term: Type 1 diabetes mellitus System Organ Class: 10027433 - Metabolism and nutrition disorders
Conditions
Interventions
Product Name: ProTrans
Product Code: WJMSC
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: Wharton´s jelly-derived mesenchymal stromal cells
Current Sponsor code: WJMSC
Other descri
Sponsors
Uppsala University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.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 2.Clinical history compatible with type 1 diabetes diagnosed less than 6 months before enrolment 3.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. 4.Mentally stable and, in the opinion of the investigator, able to comply with the procedures of the study protocol 5.Fasting plasma C-peptide concentration >0.12 nmol/L. 6.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: a)oral (except low-dose gestagen (lynestrenol and noretisteron), injectable or implanted hormonal contraceptives. b)intrauterine device c)intrauterine system (for example progestin-releasing coil) d)vasectomized male (with appropriate postvasectomy documentation of the absence of sperm in the ejaculate) Are the trial subjects under 18? yes Number of subjects for this age range: 60 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 6 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Subjects with bodyweight >100 kg 2.Subjects with unstable cardiovascular status incl. NYHA class III/IV or symptoms of angina pectoris. 3.Subjects with uncontrolled hypertension (=160/105 mmHg). 4.Subjects with active on-going infections. 5.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. 6.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. 7.Subjects with any systemic immune suppressive treatment 8.Subjects with a known demyelinating disease or with symptoms or physical examination findings consistent with possible demyelinating disease. 9.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. 10.Subjects with known, or previous, malignancy. 11.Taking oral anti-diabetic therapies or any other concomitant medication which may interfere with glucose regulation other than insulin. 12.Subjects with GFR <60 ml/min/1.73 m2 body surface. 13.Subject with any condition or any circumstance that, in the opinion of the investigator, would make it unsafe to undergo treatment with MSC. 14.Known hypersensitivity against any excipients, i.e., dimethyl sulfoxide (DMSO).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety, tolerance and efficacy after allogeneic infusion of WJMSCs intravenously in children and adolescents recently (<6 months) diagnosed with type 1 diabetes. ;Secondary Objective: Study changes in beta-cell function, metabolic control and Diabetes Treatment Satisfaction during the first year following treatment. ;Primary end point(s): Primary Safety Endpoint: Safety parameters will be evaluated in the intervention trial at each study visit and recorded as adverse events (AEs). Any grade 3 event (or higher) will be evaluated by DSMB. Primary Efficacy Endpoint: Change in C-peptide Area Under the Curve (AUC) (0-120 min) for Mixed Meal Tolerance Test (MMTT) at 12 months following WJMSC/Placebo infusion when compared to test performed before the start of treatment (baseline). ;Timepoint(s) of evaluation of this end point: Safety: Continuously from infusion of study medication until study end. Followed-up at each study visit. Efficacy: At baseline and 12 month visits. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •The proportion of study participants independent of insulin (ADA criteria) at 6 and 12 months. •The proportion of participants with daily insulin needs <0.25U/kg at 6 and 12 months. •Insulin requirement/kg body weight at 6 and 12 months. •Glycosylated Hb (HbA1c) and insulin-dose adjusted HbA1c (IDAA1c) at 6 and 12 months. •Time-in-target (4-8 mmol/l) and Time-in-range (3.9-10 mmol/l) as measured by flash glucose monitoring for 14 days at 6 and 12 months. •Change in C-peptide Area Under the Curve (AUC) (0-120 min) for Mixed Meal Tolerance Test (MMTT) at 6 months following WJMSC/Placebo infusion when compared to test performed before the start of treatment (baseline). •Change in peak C-peptide concentration during the first 6 months or the first year after treatment. ;Timepoint(s) of evaluation of this end point: At 6 and 12 month visits. | — |
Countries
Sweden
Contacts
Public ContactDpt of Endocrin and Diabet, entr 40
Uppsala University Hospital
Outcome results
None listed