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

Type1diabetes Clinical Trial

Official title:

An Open Label, Parallel Single Center Trial of Wharton's Jelly Derived Allogeneic Mesenchymal Stromal Cells Repeatedly Treated to Preserve Endogenous Insulin Production in Adult Patients Diagnosed With Type 1 Diabetes

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03973827
• Other study ID #: ProTrans-Repeat
• Secondary ID: 2018-004158-11
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: May 17, 2019
• Est. completion date: October 30, 2024

Study information

• Verified date: March 2023
• Source: NextCell Pharma Ab
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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 18 adult male patients, 18-41 years of age (inclusive at both ends) diagnosed (<3,5 years) with type 1 diabetes mellitus.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 15
• Est. completion date: October 30, 2024
• Est. primary completion date: December 10, 2020
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 41 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type1diabetes

Intervention

Drug:
• ProTrans
Single infusion of 25, 100 or 200 million cells per patient.
• Placebo
Placebo Comparator: Sham transplantation (placebo) Single infusion with albumin and dmso in sodium chloride (identical concentrations as active treatment)

Locations

Country	Name	City	State
Sweden	Karolinska Trial Alliance, Fas 1 enheten, Karolinska Universitetssjukhuset Huddinge	Huddinge

Sponsors (1)

Lead Sponsor	Collaborator
NextCell Pharma Ab

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary safety endpoint in this study is; safety parameters include adverse events, hypoglycemia and allergic reactions	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.	372 days
Primary	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.	To study changes in insulin requirements during one year following treatment .	372 days
Secondary	Number of patients insulin independent (ADA criteria) at day 372.	To study changes in insulin requirements during one year following treatment .	372 days
Secondary	Number of patients with daily insulin needs <0.25U/kg at day 372.	To study changes in insulin requirements during one year following treatment .	372 days
Secondary	HbA1c at day 372	To study changes in HbA1c during one year following treatment.	372 days
Secondary	Glucose variability (mean amplitude of glycaemic excursions and glycaemic lability index) duration derived from the continuous glucose monitoring system® at day 372	To study changes in glucose levels during one year following treatment.	372 days
Secondary	Delta change of levels of fasting C-peptide at day 372 when compared to test before start of treatment	To study changes in fasting C-peptide levels during one year following treatment.	372 days
Secondary	Numbers of patients with peak C-peptide >0.20 nmol/l, in response to the MMTT, at day 372.	To study changes in C-peptide levels during one year following treatment.	372 days