Wharton´s Jelly Derived Mesenchymal Stromal Cell Repeated Treatment of Adult Patients Diagnosed with Type I Diabetes

Phase 1

Completed

• Conditions: Type1diabetes
• Interventions: Drug: ProTrans; Other: Control

• Registration Number: NCT03973827
• Lead Sponsor: NextCell Pharma Ab

Brief Summary

An open label, parallel single centre trial of Wharton's Jelly derived allogenic mesenchymal stromal cells repeated treatment to preserve endogenous insulin production in adult patients diagnosed with type 1 diabetes

Detailed Description

This is a phase (I)/II study, and the purpose of this study is to determine whether, in adult patients diagnosed for type 1 diabetes, a repeated allogeneic infusion of WJMSCs is safe and to study changes in beta-cell function, metabolic control and Diabetes Treatment Satisfaction. The study population will consist of 15 adult male patients, 18-41 years of age (inclusive at both ends) diagnosed (\<3,5 years) with type 1 diabetes mellitus.

Study Timeline

• Study First Submitted: 2019-05-16
• Study Start: 2019-05-17
• Study First Submitted QC: 2019-06-03
• Study First Posted: 2019-06-04
• Primary Completion: 2020-12-10
• Study Completion: 2024-11-20
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-04
• Last Update Posted: 2025-03-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 15

Inclusion Criteria

1. A new written informed consent for participation of the study is required to be given before undergoing any study-specific procedures.
2. Only patients that have previously been dosed by the IMP according to protocol Protrans-1 are eligible for a second dose of Protrans.
3. No identified IMP related on-going adverse event, neither history of any adverse event that is evaluated potentially to be related to the previous IMP dosing in Protrans I.
4. Clinical history compatible with type 1 diabetes diagnosed less than 3 years before enrolment. This also includes control patients not receiving IMP.
5. Only male patients between 18-41 years of age will be included.
6. Mentally stable and, in the opinion of the investigator, able to comply with the procedures of the study protocol.

Exclusion Criteria

1. Inability to provide informed consent
2. Patients with body mass index (BMI) > 30, or weight >100 kg
3. Patients with weight <50 kg
4. Patients with unstable cardiovascular status incl. NYHA class III/IV or symptoms of angina pectoris.
5. Patients with uncontrolled hypertension (≥160/105 mmHg).
6. Patients with active on-going infections.
7. Patients with latent or previous as well as on-going therapy against tuberculosis, or exposed to tuberculosis or has travelled in areas with high risk of tuberculosis or mycosis within the last 3 months.
8. Patients with serological evidence of infection with HIV, Treponema pallidum, hepatitis B antigen (patients with serology consistent with previous vaccination and a history of vaccination are acceptable) or hepatitis C.
9. Patients with any immune suppressive treatment
10. Patients with known demyelinating disease or with symptoms or physical examination findings consistent with possible demyelinating disease.
11. Patients with known, or previous, malignancy.
12. Taking oral anti-diabetic therapies or any other concomitant medication which may interfere with glucose regulation other than insulin
13. Patients with GFR <80 ml/min/1.73 m2 body surface
14. Patients with proliferative retinopathy
15. Patient with any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo treatment with MSC.
16. Known hypersensitivity against any excipients, i.e. dimethyl sulfoxide (DMSO).- This criterion is only applicable to patients which receive study drug.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Low dose	ProTrans	3 patients receiving low dose
Medium dose	ProTrans	3 patients receiving medium dose
High dose	ProTrans	3 patients receiving high dose
Control	Control	6 patients

Primary Outcome Measures

Name	Time	Method
The primary endpoint in this study is; safety parameters include adverse events and hypoglycemia, allergic reactions, ophthalmologic examination, ECG, vital signs, laboratory assessments.	372 days	To investigate the safety and tolerance after a repeated allogeneic infusion of Whartons Jelly Mesenchymal Stromal Cells (WJMSCs) intravenously in adult patients diagnosed with type 1 diabetes after one year following the repeated treatment.
Delta-change of C-peptide AreaUnder the Curve (AUC) (0-120 min) for Mixed Meal Tolerance Test (MMTT) at day 372 following WJMSC infusion when compared to test performed before start of treatment when compared to control patients.	372 days	To study changes in insulin requirements during one year following treatment .

Secondary Outcome Measures

Name	Time	Method
Insulin requirement/kg BW at day 372. HbA1c at day 372.	372 days	To study changes in insulin requirements during one year following treatment .
HbA1c at day 372	372 days	To study changes in HbA1c during one year following treatment.
Number of patients with daily insulin needs <0.25U/kg at day 372.	372 days	To study changes in insulin requirements during one year following treatment .
Number of patients insulin independent (ADA criteria) at day 372.	372 days	To study changes in insulin requirements during one year following treatment .
Glucose variability (mean amplitude of glycaemic excursions and glycaemic lability index) duration derived from the continuous glucose monitoring system® at day 372	372 days	To study changes in glucose levels during one year following treatment.
Delta change of levels of fasting C-peptide at day 372 when compared to test before start of treatment	372 days	To study changes in fasting C-peptide levels during one year following treatment.
Numbers of patients with peak C-peptide >0.20 nmol/l, in response to the MMTT, at day 372.	372 days	To study changes in C-peptide levels during one year following treatment.
To study changes during one year following treatment in: -Insulin doses -HbA1c -Glucose variability -Diabetes Treatment Satisfaction	372 days	To study changes in C-peptide levels during one year following treatment.
To study changes in insulin requirements during one year following treatment	372 days	2. Delta-change of C-peptide AreaUnder the Curve (AUC) (0-120 min) for Mixed Meal Tolerance Test (MMTT) at day 372 following WJMSC infusion when compared to test performed before start of treatment when compared to control patients.; Description:

Trial Locations

Locations (1)

Karolinska Trial Alliance, Fas 1 enheten, Karolinska Universitetssjukhuset Huddinge; 🇸🇪 Huddinge, Sweden