Ongoing Clinical Trials for Hyperinsulinaemic Hypoglycaemia
There are currently 3 ongoing clinical trials investigating treatments for hyperinsulinaemic hypoglycaemia, a condition where excessive insulin production leads to dangerously low blood sugar levels. These trials are testing medications including ersodetug, RZ358, and pasireotide across multiple European countries, focusing on different patient populations including those with tumor-related causes, congenital forms, and post-bariatric surgery complications.
Clinical trial locations
- Belgium
- Bulgaria
- Denmark
- France
- Germany
- Greece
- Italy
- Netherlands
- Spain
Study on Ersodetug for Patients with Uncontrolled Low Blood Sugar Due to Tumor-Related High Insulin Levels
This Phase 3 trial is investigating ersodetug (also known as RZ358), an anti-insulin receptor antibody, for adults with tumor-associated hyperinsulinism. This condition occurs when tumors cause excessive insulin production, leading to dangerously low blood sugar levels.
Main inclusion criteria: Eligible participants must be at least 18 years old with a confirmed diagnosis of tumor-associated hyperinsulinism. They must experience at least 3 episodes of low blood sugar per week with glucose levels below 54 mg/dL or episodes requiring assistance due to confusion or physical symptoms. The condition must be difficult to control despite standard treatments. Participants need a life expectancy of at least 3 months and an ECOG performance status of 2 or better, meaning they can care for themselves with limited work ability. A multidisciplinary team including an oncologist must evaluate eligibility.
Main exclusion criteria: Participants cannot join if their low blood sugar is not caused by tumor-associated hyperinsulinism or if it is adequately controlled with current treatment. Those with medical conditions that might interfere with study results, taking medications that could interact with ersodetug, or with known allergies to the medication are excluded. Pregnant or breastfeeding women, recent participants in other drug trials, and those unable to comply with study procedures are also ineligible.
Focus and goals: The study aims to evaluate whether ersodetug, when added to standard treatments, can reduce the frequency and severity of low blood sugar episodes. Researchers will monitor hypoglycemic events weekly and measure blood glucose levels continuously. For hospitalized patients requiring intravenous glucose, the study will track changes in glucose infusion rates and time to discontinue IV glucose.
Investigational drug: Ersodetug is administered through intravenous infusion over an 8-week treatment period, with the possibility of an open-label extension phase for long-term safety evaluation. The medication works as an add-on to existing standard care therapies.
Study on RZ358 for Treating Congenital Hyperinsulinism in Patients
This double-blind, placebo-controlled trial is studying RZ358, a human monoclonal antibody that blocks insulin receptors, for patients with congenital hyperinsulinism. This genetic disorder causes insulin-producing cells in the pancreas to release too much insulin even when blood sugar levels are low.
Main inclusion criteria: Participants must be between 3 months (corrected for gestational age if under 9 months) and 45 years old with a confirmed clinical diagnosis of congenital hyperinsulinism. They must have failed to achieve adequate blood sugar control despite trying standard medical treatments like diazoxide and somatostatin analogs. Participants need to experience at least 3 episodes of low blood sugar (below 70 mg/dL) per week with an average daily time in hypoglycemia of at least 8% during screening. A liver ultrasound must show no significant abnormalities. Women of childbearing potential must have a negative pregnancy test and agree to effective contraception during the study and for 3 months afterward.
Main exclusion criteria: The trial excludes patients with serious health conditions that might interfere with the study, pregnant or breastfeeding women, recent participants in other clinical trials, those with allergies to the study medication, and individuals unable to follow study procedures. Patients with a history of drug or alcohol abuse, certain heart conditions, severe kidney or liver problems, or taking medications that might interfere with the study drug are also excluded.
Focus and goals: The 24-week study will assess whether RZ358 can reduce the frequency of hypoglycemic events and help patients maintain stable blood sugar levels. Regular monitoring will include self-monitored blood glucose and continuous glucose monitoring devices, along with regular safety assessments including laboratory tests and physical exams.
Investigational drug: RZ358 is administered intravenously and works by blocking the effects of insulin on its receptor, helping to prevent dangerously low blood sugar levels. It is classified as an anti-hypoglycemic agent.
Study on the Effects of Pasireotide in Patients with Low Blood Sugar After Bariatric Surgery
This trial evaluates pasireotide diaspartate, a somatostatin analog, for managing post-bariatric hypoglycemia, a condition where blood sugar drops too low after eating in people who have had weight-loss surgery.
Main inclusion criteria: Participants must be adults 18 years or older who underwent bariatric surgery more than 6 months prior. They must have a documented diagnosis of post-bariatric hypoglycemia with symptoms that improve after eating carbohydrates. Eligible participants need to have experienced at least 4 episodes of post-meal low blood sugar during a 28-day period, defined as blood sugar below 54 mg/dL, symptoms of neuroglycopenia (brain not getting enough sugar), or severe hypoglycemic events. Dietary modifications alone must have been insufficient to control symptoms. A Karnofsky Performance Status of 60 or higher is required, meaning participants can take care of most personal needs with some help. Previous treatments for post-bariatric hypoglycemia must be stopped for specific periods before joining, and participants must be able to self-inject the medication after receiving training.
Main exclusion criteria: Patients without a post-bariatric hypoglycemia diagnosis, those outside the specified age range, those belonging to non-included clinical trial groups, and vulnerable populations requiring special protection cannot participate.
Focus and goals: The 12-week initial treatment phase aims to determine the most effective dose of pasireotide (50, 100, or 200 micrograms three times daily) for managing blood sugar levels. Blood glucose monitoring will track changes from baseline, and the frequency and severity of hypoglycemic events will be assessed. An optional extension phase allows continued treatment and monitoring for up to 48 weeks.
Investigational drug: Pasireotide is administered as a subcutaneous injection (under the skin) and works by mimicking somatostatin, a hormone that inhibits the release of several other hormones, thereby helping to regulate blood sugar levels after meals.
Summary
These three clinical trials address different forms of hyperinsulinaemic hypoglycaemia, reflecting the diverse causes of excessive insulin production. France emerges as the most active location, hosting all three trials, while Spain participates in two studies. The trials target distinct patient populations: adults with tumor-related causes, patients aged 3 months to 45 years with congenital forms, and adults experiencing complications following bariatric surgery.
Two of the trials are investigating medications that directly block insulin signaling—ersodetug and RZ358—both delivered intravenously, while the third evaluates pasireotide, a hormone analog given by injection under the skin. The studies employ different treatment durations ranging from 8 to 24 weeks for the main phases, with extension periods available in some cases for long-term safety evaluation. All trials use rigorous monitoring of blood glucose levels and hypoglycemic episodes to assess treatment effectiveness.
The diversity of approaches and patient populations in these trials highlights the complex nature of hyperinsulinaemic hypoglycaemia and the need for tailored treatments depending on the underlying cause. These studies may provide important new options for patients whose condition remains poorly controlled with existing therapies.
