Study to Evaluate Safety and Efficacy of IBsolvMIR in Islet Transplantation

Trial details

Who runs it

TikoMed AB

Trial code

NCT03867851

Record updated

16 May 2024

Original description

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.Read full original descriptionShow less

Open, Randomized, Active Comparator-controlled, Multi-Center Study to Evaluate Safety and Efficacy of IBsolvMIR® in Islet Transplantation

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.

Inclusion: 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.

Exclusion: 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 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 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 any condition or any circumstance that in the opinion of the investigator would make it unsafe to undergo treatment with IBsolvMIR; Patients participating in or having participated in any other clinical drug studies in the past four weeks; Previous known heparin-induced thrombocytopenia (HIT); Any history of malignancy except for completely resected squamous or basal cell carcinoma of the skin; Patients with active infections, unless treatment is not judged necessary by the investigators; Patients with active peptic ulcer disease, symptomatic gallstones or portal hypertension; Patients of childbearing potential not willing to use adequate double contraception with < 1% failure rate after the screening visit until the last visit; Patients with psychological conditions that make it unsafe to undergo islet transplantation or which preclude compliance with prescribed therapy; History of bleeding disorders; History of severe hypersensitivity; Patients with severe hepatic or renal impairment; Consistently abnormal liver function tests (> 1.5 x ULN on two consecutive measurements > 2 weeks apart) at screening; Increased risk for thrombosis (ex. homozygous APC-resistance) or bleeding (INR>1.5); HbA1c > IFCC 100 mmol/mol, at screening; Patients with body mass index (BMI) > 30; Insulin requirement > 0.7 Unit/kg/day at screening; Proliferative untreated diabetic retinopathy; Patients who are pregnant or breastfeeding, or who intend to become pregnant; Active alcohol or substance abuse; Patients with evidence of high-level sensitization (PRA> 50% with flow cytometry).

ClinicalTrials.gov NCT03867851