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

Type1diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05061030
• Other study ID #: WJMSC-P01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 14, 2022
• Est. completion date: December 2028

Study information

• Verified date: November 2023
• Source: Uppsala University Hospital
• Contact: Per-Ola Carlsson, MD, PhD
• Phone: +46186110000
• Email: per-ola.carlsson[@]mcb.uu.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: December 2028
• Est. primary completion date: September 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 7 Years to 21 Years

Eligibility

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).

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type1diabetes

Intervention

Biological:
• the ATMP Protrans
Protrans consists of Wharton's jelly derived mesenchymal stromal cells

Locations

Country	Name	City	State
Sweden	Uppsala University Hospital	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Uppsala University Hospital

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Gender differences	Differences in parameters of primary and secondary endpoints between genders	6 months
Other	Gender differences	Differences in parameters of primary and secondary endpoints between genders	12 months
Other	HLA class 1 genotypes	Differences in parameters of primary and secondary endpoints between HLA class 1 genotypes	6 months
Other	HLA class 1 genotypes	Differences in parameters of primary and secondary endpoints between HLA class 1 genotypes	12 months
Other	age	Differences in parameters of primary and secondary endpoints between ages 7-11 and 12-21	6 months
Other	age	Differences in parameters of primary and secondary endpoints between ages 7-11 and 12-21	12 months
Other	Autoantibodies	Change of levels of diabetes-related autoantibodies when compared to test before the start of treatment (baseline)	6 months
Other	Autoantibodies	Change of levels of diabetes-related autoantibodies when compared to test before the start of treatment (baseline)	12 months
Other	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
Other	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
Primary	Safety at one year evaluated as adverse events	Safety parameters will be evaluated at each study visit and recorded as adverse events.	One year
Primary	Safety at five years evaluated as adverse events	Safety parameters will be evaluated at each study visit and recorded as adverse events.	Five years
Primary	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	Insulin independency	The proportion of study participants independent of insulin at 6 months	One year
Secondary	Insulin independency	The proportion of study participants independent of insulin at 12 months	One year
Secondary	Low insulin needs	The proportion of study participants with daily insulin needs <0.25 U/kg at 6 months	6 months
Secondary	Low insulin needs	The proportion of study participants with daily insulin needs <0.25 U/kg at 12 months	12 months
Secondary	Insulin needs	Insulin requirement/kg body weigh at 6 months	6 months
Secondary	Insulin needs	Insulin requirement/kg body weigh at 12 months	12 months
Secondary	HbA1c	HbA1c at 6 months	6 months
Secondary	HbA1c	HbA1c at 12 months	12 months
Secondary	Time in target	Time in target (4-8 mmol/l) as measured by flash glucose monitoring for 14 days at 6 months	6 months
Secondary	Time in target	Time in target (4-8 mmol/l) as measured by flash glucose monitoring for 14 days at 12 months	12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in peak C-peptide	Change in peak C-peptide concentration during the first 6 months	6 months
Secondary	Change in peak C-peptide	Change in peak C-peptide concentration during the first 12 months	12 months