Mesenchymal Stromal Cells to Treat Type 1 Diabetes in Children and Adolescents

A Double-blinded, Randomized, Parallel, Placebo-controlled Trial of Wharton's Jelly-derived Allogeneic Mesenchymal Stromal Cells to Treat Type 1 Diabetes in Children and Adolescents

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Type1diabetes
• Intervention / Treatment: Biological: the ATMP Protrans

• Study Type: Interventional
• Enrollment (Estimated): 66
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Uppsala, Sweden, 75185
    • Uppsala University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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:

   1. oral (except low-dose gestagen (lynestrenol and noretisteron), injectable or implanted hormonal contraceptives.
   2. intrauterine device
   3. intrauterine system (for example progestin-releasing coil)
   4. vasectomized male (with appropriate postvasectomy documentation of the absence of sperm in the ejaculate)

Exclusion Criteria:

1. Subjects with body weight >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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	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

Other Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Uppsala University Hospital
• Investigators: Principal Investigator: Per-Ola Carlsson, MD, PhD, Uppsala University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2022
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: September 20, 2021
• First Submitted That Met QC Criteria: September 20, 2021
• First Posted (Actual): September 29, 2021

Study Record Updates

• Last Update Posted (Actual): April 28, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Autoimmune Diseases; Immune System Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: WJMSC-P01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No