Gaucher DiseasePhase 2NCT00041535
OGT 918-006: A Phase I/II Randomized, Controlled Study of OGT 918 in Patients With Neuronopathic Gaucher Disease
A Phase 2 study testing OGT 918 in people with Gaucher Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 years and older
- Conditions the study is for
- Gaucher Disease
- What is being tested?
- OGT 918
- How many people
- 30 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 5 Jul 2002to 21 Mar 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with neuronopathic Gaucher disease, confirmed by clinical diagnosis, who if receiving enzyme replacement therapy have been stable on enzyme replacement therapy for at least 6 months or have successfully undergone a bone marrow transplant at least one year prior to study entry.
- Patients who are at least 4 years old and can swallow a capsule.
Who cannot join
- Patients younger than 18 years who are unable to give informed assent and/or whose legal guardian is unable to provide informed consent.
- Patients aged 18 and over who cannot provide informed consent and/or whose legal guardian is unable to provide witnessed informed consent.
- Fertile patients, who at the time of the study could be sexually active, and who do not agree to use adequate contraception throughout the study and for three months after cessation of OGT 918 treatment.
- Patients who cannot tolerate the study procedures or who are unable to travel to the study center as required by this protocol.
- Patients currently undergoing therapy with other investigational agents or patients taking drugs or food supplements which may interfere with gastrointestinal absorption or motility.
- Patients suffering from clinically significant diarrhea (greater than 3 liquid stools per day for greater than 7 days) without definable cause within 3 months of the Screening Visit, or who have a history of significant gastrointestinal disorders.
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- Patients with an intercurrent medical condition that would render them unsuitable for the study e.g. HIV, hepatitis infection.
- Patients who in the opinion of the investigator (for whatever reason) are thought to be unsuitable for the study.
- Patients with an adjusted Creatinine Clearance of less than 70 ml/min/1.73m(2) (CrCl less than 70).
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Phase I/II Randomized, Controlled Study of OGT 918 in Patients With Neuronopathic Gaucher Disease
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.
Read more
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 main study and enter the extension study will receive OGT 918.
During a 4-week screening period, eye movement velocity will be measured. These assessments will be repeated at months 12 and 24. Also at screening and months 12 and 24, the following tests will be done: MRI/CT, to measure spleen and liver volume; pulmonary imaging (by X-ray) and function tests; nerve conduction velocity studies and neuropsychological assessments; evoked response studies (to measure how the brain conducts electrical messages); and tremor measurements. Additional assessments for tremor will be conducted at months 6 and 18.
Plasma samples will be obtained every 3 months to measure disease markers and safety profiles. Proteasome samples will be taken at screening and month 6 to identify proteins that may be associated with Gaucher disease. Blood will be obtained at month 1 from the first 6 consenting patients who have been randomly assigned to take OGT 918. These patients will also have a cerebrospinal fluid sample taken by lumbar puncture at month 1. These samples will be measured for how much OGT 918 is present.
All patients receiving OGT 918 will have an initial assessment 1 week after beginning treatment to evaluate tolerance of the therapy. Clinic visits will be every 3 months. All patients will be asked to keep a simple diary of adverse events and dietary information. Dose levels may be reduced if a patient experiences severe gastrointestinal problems.
Read the detailed description
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 will be extended, up to a total of 12 additional months, to collect safety and efficacy data. The length of the extension study will be dependent on the results of the final analysis. All patients completing the main study, including those initially randomized to the no treatment group, will be able to participate in the extension study unless there are safety issues to prohibit this. All patients in the extension study will receive OGT 918.
Disease activity assessments will be conducted as indicated in the study flow charts. For a complete description of all study assessments, please refer to Section 7 of the main protocol. Where possible, study assessments will be blinded.
The effect of OGT 918 on the electro-oculographic characteristics of saccadic activity, specifically the amplitude/velocity characteristics (main sequence), will be the primary outcome variable. Saccadic velocity-amplitude relationship is decreased in neuronopathic Gaucher patients. This study will assess whether OGT 918 therapy is capable of improving or stopping any further deterioration of this ocular function.
- Conditions
- Gaucher Disease
- Being tested
- OGT 918
- Keywords
- Eye Movements, Saccades, Metabolic, Lysosomal, Myoclonus, Gaucher Disease, Neuronopathic Gaucher Disease
- Medical subject headings
- Gaucher Disease, Myoclonus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OGT 918Drug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2002 (estimated)
- Study start5 Jul 2002
- Study completion21 Mar 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Gaucher DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 30 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00041535
- Sponsor's protocol ID
- 020243
- Other IDs
- 02-N-0243
- Status last verified
- 3 Mar 2008
- First submitted
- 9 Jul 2002
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Platt FM, Neises GR, Dwek RA, Butters TD. N-butyldeoxynojirimycin is a novel inhibitor of glycolipid biosynthesis. J Biol Chem. 1994 Mar 18;269(11):8362-5.
PubMed 8132559
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Randomized, Controlled Study of OGT 918 in Patients With Neuronopathic Gaucher Disease
- ClinicalTrials.gov ID
- NCT00041535
- Acronym / sponsor ID
- 020243
- Conditions
- Gaucher Disease
- Keywords
- Eye Movements, Saccades, Metabolic, Lysosomal, Myoclonus, Gaucher Disease, Neuronopathic Gaucher Disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 5 Jul 2002
- Study completion
- 21 Mar 2007
- First posted
- 10 Jul 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 main study and enter the extension study will receive OGT 918.
During a 4-week screening period, eye movement velocity will be measured. These assessments will be repeated at months 12 and 24. Also at screening and months 12 and 24, the following tests will be done: MRI/CT, to measure spleen and liver volume; pulmonary imaging (by X-ray) and function tests; nerve conduction velocity studies and neuropsychological assessments; evoked response studies (to measure how the brain conducts electrical messages); and tremor measurements. Additional assessments for tremor will be conducted at months 6 and 18.
Plasma samples will be obtained every 3 months to measure disease markers and safety profiles. Proteasome samples will be taken at screening and month 6 to identify proteins that may be associated with Gaucher disease. Blood will be obtained at month 1 from the first 6 consenting patients who have been randomly assigned to take OGT 918. These patients will also have a cerebrospinal fluid sample taken by lumbar puncture at month 1. These samples will be measured for how much OGT 918 is present.
All patients receiving OGT 918 will have an initial assessment 1 week after beginning treatment to evaluate tolerance of the therapy. Clinic visits will be every 3 months. All patients will be asked to keep a simple diary of adverse events and dietary information. Dose levels may be reduced if a patient experiences severe gastrointestinal problems.
Detailed description
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 will be extended, up to a total of 12 additional months, to collect safety and efficacy data. The length of the extension study will be dependent on the results of the final analysis. All patients completing the main study, including those initially randomized to the no treatment group, will be able to participate in the extension study unless there are safety issues to prohibit this. All patients in the extension study will receive OGT 918.
Disease activity assessments will be conducted as indicated in the study flow charts. For a complete description of all study assessments, please refer to Section 7 of the main protocol. Where possible, study assessments will be blinded.
The effect of OGT 918 on the electro-oculographic characteristics of saccadic activity, specifically the amplitude/velocity characteristics (main sequence), will be the primary outcome variable. Saccadic velocity-amplitude relationship is decreased in neuronopathic Gaucher patients. This study will assess whether OGT 918 therapy is capable of improving or stopping any further deterioration of this ocular function.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 4 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (2 listed)
- Patients with neuronopathic Gaucher disease, confirmed by clinical diagnosis, who if receiving enzyme replacement therapy have been stable on enzyme replacement therapy for at least 6 months or have successfully undergone a bone marrow transplant at least one year prior to study entry.
- Patients who are at least 4 years old and can swallow a capsule.
Key exclusion criteria (9 listed)
- Patients younger than 18 years who are unable to give informed assent and/or whose legal guardian is unable to provide informed consent.
- Patients aged 18 and over who cannot provide informed consent and/or whose legal guardian is unable to provide witnessed informed consent.
- Fertile patients, who at the time of the study could be sexually active, and who do not agree to use adequate contraception throughout the study and for three months after cessation of OGT 918 treatment.
- Patients who cannot tolerate the study procedures or who are unable to travel to the study center as required by this protocol.
- Patients currently undergoing therapy with other investigational agents or patients taking drugs or food supplements which may interfere with gastrointestinal absorption or motility.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| OGT 918 | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 8132559Platt FM, Neises GR, Dwek RA, Butters TD. N-butyldeoxynojirimycin is a novel inhibitor of glycolipid biosynthesis. J Biol Chem. 1994 Mar 18;269(11):8362-5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing OGT 918 in people with Gaucher Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00041535, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.