Study to Evaluate Safety and Efficacy of IBsolvMIR in Islet Transplantation

NCT03867851 | Terminated Phase 2 DMC

• 1 other identifier: NNCIT-02
• Study Type: interventional
• Target: 7
• Locations: 3 countries
• Sites: 5

Brief Summary

This is a Phase II open, randomized, active comparator-controlled multi center study in patients with severe type-1 diabetes. This is a two-armed study where patients are randomized in a 2:1 ratio between IBsolvMIR and heparin. Eighteen patients are planned to be included. The study consists of up to 8 visits; screening, transplantation surgery with bolus administration of study drug or active comparator, IBsolvMIR doses on day 1, 3 and 6 after surgery, follow up visits on day 7 and 14, and follow-up phone call on day 44. The primary endpoint is to study AEs up to 44 days following study drug administration. The secondary endpoints are to evaluate changes in TAT, C-peptide, C3a and HGF at baseline and during the first 24 hours after study drug administration, as well as evaluate a change in levels of C-peptide-glucose-creatinine ratio on day 14 compared to baseline.

Conditions

Diabetes Mellitus, Type 1

Outcome Measures

Primary Outcomes (2)

• Bleeding events

  Bleeding events after islet transplantation with total dose of 27 mg/kg BW IBsolvMIR in comparison to active comparator Heparin

  Up to 44 days.

• Other AEs/SAEs after islet transplantation

  Other AEs/SAEs after islet transplantation with total dose of 27 mg/kg BW IBsolvMIR in comparison to active comparator Heparin

  Up to 44 days.

Secondary Outcomes (2)

• Difference between groups in levels of biomarkers

  Within 7 days.

• Change in C-peptide / (glucose x creatinine) ratio (CPGCR)

  Within 14 days.

Study Arms (2)

IBsolvMIR

EXPERIMENTAL

Study drug IBsolvMIR administered intravenously at 18 mg/kg on day of transplantation and 3 mg/kg on post-operative days 1, 3, 6.

Drug: IBsolvMIR

Heparin

ACTIVE COMPARATOR

Heparin treatment according to clinical praxis.

Drug: Heparin

Interventions

IBsolvMIR DRUG

Study drug IBsolvMIR

IBsolvMIR

Heparin DRUG

Clinical praxis

Heparin

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patient on a waiting list for islet transplantation
• Male and female patients age 18 to 60 years of age.
• Ability to understand and provide written informed consent.
• Mentally stable and able to comply with the procedures of the study protocol.
• Clinical history compatible with type 1 diabetes with onset of disease at \< 40 years of age and insulin-dependence for \> 5 years at the time of enrolment.
• Documented C-peptide \<0.1 nmol/L before first islet transplantation (stimulated in response to a MMTT or other confirmatory method).
• All subjects must have received medical treatment of their diabetes under the guidance from an experienced endocrinologist. If not previously transplanted the patient must also have;
• At least one episode of severe hypoglycemia in the past 1 year defined as an event with at least one of the following symptoms; memory loss, confusion, uncontrollable behavior, unusual difficulty in awakening, suspected seizure, loss of consciousness, or visual symptoms, in which the subject was unable to treat him/herself and which was associated with either a blood/plasma glucose level \< 54 mg/dl \[3.0 mmol/L\] or prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration OR
• Reduced awareness of hypoglycemia as defined by a Clarke score of 4 or more.

You may not qualify if:

• Patients with prior organ transplants other than a kidney graft and/or islets. A previous pancreas transplant can be accepted if it failed within the first week due to thrombosis and the graft was removed.
• Patients with body mass index (BMI) \> 30.
• Insulin requirement \> 0.7 Unit/kg/day at screening.
• Consistently abnormal liver function tests (\> 1.5 x ULN on two consecutive measurements \> 2 weeks apart) at screening.
• Proliferative untreated diabetic retinopathy
• Increased risk for thrombosis (ex. homozygous APC-resistance) or bleeding (INR\>1.5)
• Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin
• Patients with increased cardiac risk defined as;
• unstable coronary artery disease requiring hospitalization or revascularization within 6 months prior to baseline visit
• chronic heart failure which required hospitalization 30 days prior to baseline visit
• Patients with active infections, unless treatment is not judged necessary by the investigators
• Patients with serological evidence of infection with HIV, hepatitis B (patients with serology consistent with previous vaccination and a history of vaccination are acceptable) or hepatitis C.
• Patients with active peptic ulcer disease, symptomatic gallstones or portal hypertension.
• Patients who are pregnant or breastfeeding, or who intend to become pregnant.
• Patients of childbearing potential not willing to use adequate double contraception with \< 1% failure rate after the screening visit until the last visit.

Sponsors & Collaborators

• TikoMed AB: lead

Study Sites (5)

Leiden University Medical Center

Leiden, South Holland, 2300 RC, Netherlands

Location

Oslo Universitetssykehus HF

Oslo, Norway

Location

Sahlgrenska sjukhuset

Gothenburg, Sweden

Location

Karolinska Universitetssjukhuset Huddinge

Stockholm, Sweden

Location

Akademiska sjukhuset

Uppsala, Sweden

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Heparin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2019
• First Posted: March 8, 2019
• Study Start: February 8, 2021
• Primary Completion: May 13, 2024
• Study Completion: May 13, 2024
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); NO (1); SE (3)