PROTRANS (synonym: Navicorcel) for Type 1 diabetes

Stratification factors

• Age stratum (12-21 vs 7-11 years)

Inclusion criteria

• {"criterion_text":"- 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"}
• {"criterion_text":"- Clinical history compatible with type 1 diabetes diagnosed less than 6 months before enrolment"}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Mentally stable and, in the opinion of the investigator, able to comply with the procedures of the study protocol."}
• {"criterion_text":"- Fasting plasma C-peptide concentration >0.12 nmol/L."}
• {"criterion_text":"- 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)"}

Exclusion criteria

• {"criterion_text":"- Subjects with bodyweight >100 kg"}
• {"criterion_text":"- Subjects with known, or previous, malignancy."}
• {"criterion_text":"- Taking oral anti-diabetic therapies or any other concomitant medication which may interfere with glucose regulation other than insulin."}
• {"criterion_text":"- Subjects with GFR <60 ml/min/1.73 m2 body surface."}
• {"criterion_text":"- Subject with any condition or any circumstance that, in the opinion of the investigator, would make it unsafe to undergo treatment with MSC."}
• {"criterion_text":"- Known hypersensitivity against any excipients, i.e., dimethyl sulfoxide (DMSO)."}
• {"criterion_text":"- Subjects with unstable cardiovascular status incl. NYHA class III/IV or symptoms of angina pectoris."}
• {"criterion_text":"- Subjects with uncontrolled hypertension (≥160/105 mmHg)."}
• {"criterion_text":"- Subjects with active on-going infections."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Subjects with any systemic immune suppressive treatment"}
• {"criterion_text":"- Subjects with a known demyelinating disease or with symptoms or physical examination findings consistent with possible demyelinating disease."}
• {"criterion_text":"- 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."}

Primary endpoints

• {"endpoint_text":"- Safety 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. Efficacy 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).","definition_or_measurement_approach":"Safety: evaluated at each study visit and recorded as adverse events (AEs); any grade 3 or higher event will be evaluated by DSMB. Efficacy: Change in C-peptide Area Under the Curve (AUC) (0-120 min) measured by Mixed Meal Tolerance Test (MMTT) at 12 months compared to baseline."}

Secondary endpoints

• {"endpoint_text":"- The proportion of study participants independent of insulin (ADA criteria) at 6 and 12 months.","definition_or_measurement_approach":"Proportion meeting ADA criteria for insulin independence at 6 and 12 months."}
• {"endpoint_text":"- The proportion of participants with daily insulin needs <0.25U/kg at 6 and 12 months.","definition_or_measurement_approach":"Proportion with daily insulin requirement <0.25 U/kg at 6 and 12 months."}
• {"endpoint_text":"- Insulin requirement/kg body weight at 6 and 12 months.","definition_or_measurement_approach":"Measured insulin dose per kg body weight at 6 and 12 months."}
• {"endpoint_text":"- Glycosylated Hb (HbA1c) and insulin-dose adjusted HbA1c (IDAA1c) at 6 and 12 months.","definition_or_measurement_approach":"HbA1c and IDAA1c measured at 6 and 12 months."}
• {"endpoint_text":"- \tTime-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.","definition_or_measurement_approach":"Flash glucose monitoring over 14 days to calculate time-in-target (4-8 mmol/L) and time-in-range (3.9-10 mmol/L) at 6 and 12 months."}
• {"endpoint_text":"- \tChange 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).","definition_or_measurement_approach":"Change in C-peptide AUC (0-120 min) measured by MMTT at 6 months vs baseline."}
• {"endpoint_text":"- Change in peak C-peptide concentration during the first 6 months or the first year after treatment","definition_or_measurement_approach":"Change in peak C-peptide concentration measured during first 6 months or first year post-treatment."}

Sweden

Earliest CTIS Part Ii Submission Date

24-09-2024

Latest Decision Or Authorization Date

12-11-2024

Processing Time Days

49

Number Of Sites

2

Number Of Participants

66

Primary sponsor

Full Name

Region Uppsala

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Sweden