WJMSC-P01

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Uppsala

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

12 Nov 2024 → ongoing

Decision date (initial)

2024-11-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-518270-14-00

EudraCT number

2020-004520-42

ClinicalTrials.gov

NCT05061030

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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 objectives 1

1. Study changes in beta-cell function, metabolic control and Diabetes Treatment Satisfaction during the first year following treatment.

Conditions and MedDRA coding

Type 1 diabetes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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)

Exclusion criteria 14

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).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 7

1. The proportion of study participants independent of insulin (ADA criteria) at 6 and 12 months.
2. The proportion of participants with daily insulin needs <0.25U/kg at 6 and 12 months.
3. Insulin requirement/kg body weight at 6 and 12 months.
4. Glycosylated Hb (HbA1c) and insulin-dose adjusted HbA1c (IDAA1c) at 6 and 12 months.
5. · 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.
6. · 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).
7. Change in peak C-peptide concentration during the first 6 months or the first year after treatment

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Uppsala

Sponsor organisation

Region Uppsala

Address

Storgatan 27, Uppsala Domkyrkofors. Uppsala Domkyrkofors.

City

Uppsala

Postcode

753 31

Country

Sweden

Scientific contact point

Organisation

Region Uppsala

Contact name

Department of Endocrin and Diabetes

Public contact point

Organisation

Region Uppsala

Contact name

Department of Endocrin and Diabetes

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications