Clinical Trial: OGT 918-006: A Phase I/II Randomized, Controlled Study of OGT 918 in Patients With Neuronopathic Gaucher Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I/II Randomized, Controlled Study of OGT 918 in Patients With Neuronopathic Gaucher Disease

Brief Summary:

Gaucher disease is an inherited functional deficiency of glucocerebrosidase. This enzyme breaks down a fatty substance (lipid) called glucocerebroside, which is present in all cells of the body. When cells renew themselves, the lipids must be broken down and discarded. Because the enzyme does not function well, the lipid builds up in certain tissues, such as the liver and spleen. The nervous system is involved as well; memory is impaired and it is difficult to move the eyes from side to side. It has been shown that repeated infusions of glucocerebrosidase help break down the stored lipid. However, this treatment does not improve any neurological symptoms.

A medicine called OGT 918 has been shown to slow the production of the lipid that builds up in Gaucher disease. It also has been shown to enter the brain. It is hoped that taking OGT 918 will reduce the storage of glycolipids in cells and improve the neurological symptoms of the disease. This clinical trial seeks to evaluate OGT 918 as a treatment for neuronopathic Gaucher disease by assessing changes in eye movement velocity. A secondary goal is to assess the clinical safety and tolerability of OGT 918 therapy.

Up to 30 patients from the National Institutes of Health and the Institute of Child Health (London) will be randomly assigned to OGT 918 or no treatment for 12 months. Study participants must be clinically diagnosed with neuronopathic Gaucher disease, 12 years of age or older, and able to swallow capsules. They must have been stable on ERT for at least 6 months before the study.

Patients receiving OGT 918 will receive a dose of 200 mg OGT 918 three times daily. Data analysis will be done after 12 months. The study will be extended up to 12 months to collect safety and efficacy data. All patients who complete the ma

Detailed Summary:

Gaucher disease is an inherited functional deficiency of glucocerebrosidase (beta-glucosidase) which leads to glycolipid accumulation in various tissues. OGT 918 is a reversible inhibitor of glucosylceramide synthase, a key enzyme in the synthesis of glycolipids, and has shown beneficial effects in a clinical study in type 1 Gaucher disease.

The primary objective of this clinical trial is to evaluate OGT 918 as a treatment for neuronopathic Gaucher disease by assessing changes in saccadic eye movement velocity. Other markers of the disease will also be assessed, including neurological and pulmonary involvement. Secondary objectives are to assess the clinical safety and tolerability of OGT 918 therapy.

Up to 30 patients, recruited from the National Institutes Health, Bethesda, USA and the Institute of Child Health, London, U.K. will be randomized to OGT 918 or no treatment in a 2:1 ratio for the 12 month study period. Patients will be clinically diagnosed with neuronopathic Gaucher disease, 12 years of age or older, on a stable dose of enzyme replacement therapy (ERT) for at least 6 months and be able to swallow capsules. Randomization will be stratified based on whether or not the patient has undergone a splenectomy.

All patients will follow an identical visit schedule. Patients aged 12 years or over randomized to receive OGT 918 will commence treatment at a dose of 200 mg (2 x 100 mg capsules) OGT 918 three times daily. As some patients may experience initial gastrointestinal intolerance this dose may be modified, however the aim will be to maintain patients at the highest tolerable dose in order to achieve the most clinical benefit. Data analysis is planned, comparing OGT 918 to the no treatment group, when all patients have completed 12 months of the study. The study wil
Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

Current Primary Outcome:

Original Primary Outcome:

Current Secondary Outcome:

Original Secondary Outcome:

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: July 9, 2002
Date Started: July 5, 2002
Date Completion: March 21, 2007
Last Updated: January 24, 2017
Last Verified: March 3, 2008