GNE MyopathyPhase 2GNE MyopathyNCT01517880
A Phase 2 Study to Evaluate the Dose and Pharmacodynamic Efficacy of Sialic Acid-Extended Release (SA-ER) Tablets in Patients With GNE Myopathy or Hereditary Inclusion Body Myopathy
A Phase 2 study testing Sialic Acid Extended Release (SA-ER) in people with GNE Myopathy and Hereditary Inclusion Body Myopathy, run by Ultragenyx Pharmaceutical Inc at 4 sites in 2 countries.
Trial summary
GNE myopathy or hereditary inclusion body myopathy (HIBM) is a severe progressive metabolic myopathy caused by a defect in the biosynthetic pathway for sialic acid (SA). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- GNE Myopathy, Hereditary Inclusion Body Myopathy
- What is being tested?
- Sialic Acid Extended Release (SA-ER)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 4 sitesin 2 countries
- Study dates
- May 2012to Nov 2013
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must be between 18 and 65 years of age, inclusive.
- Must be willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures.
- Must have a documented diagnosis of GNE myopathy, HIBM, distal myopathy with rimmed vacuoles (DMRV), or Nonaka disease due to previously demonstrated mutations in the gene encoding the GNE/MNK enzyme. Genotyping will not be conducted in this protocol.
- Must be able to walk 20 meters independently (may use orthotics and assistive devices).
- Must be able to provide reproducible force in bilateral elbow flexors and knee extensors during hand-held dynamometry testing (unilateral between test variability of < 15% for both muscle groups).
- Must be willing and able to comply with all study procedures including fine needle muscle biopsies of the upper (e.g., triceps brachii or posterior deltoid) and lower (e.g., biceps femoris or vastus lateralis) extremities at Baseline and 24 and 48 weeks.
- Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study.
- Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause for at least two years, or have had tubal ligation at least one year prior to Screening, or who have had total hysterectomy.
Who cannot join
- Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
- Use of any investigational product or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
- Ingestion of N-acetyl-D-mannosamine (ManNAc), SA, or related metabolites; intravenous immune globulin (IVIG); or anything that can be metabolized to produce SA in the body for the prior 60 days.
- Has a condition of such severity and acuity, in the opinion of the investigator, that it warrants immediate surgical intervention or other treatment or may not allow safe participation in the study.
- Has had any hypersensitivity to SA or its excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects.
- Has a concurrent disease or condition that, in the view of the principal investigator, places the subject at high risk of poor treatment compliance or of not completing the study, or would interfere with study participation or would affect safety.
- Has serum transaminase (i.e., alanine aminotransferase [ALT], aspartate aminotransferase [AST], or gamma-glutamyl transpeptidase [GGT]) levels greater than three times the upper limit of normal or serum creatinine of greater than 2.0 mg/dL.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United States3 sites
UCLA Medical Center
Los Angeles, California, 90095
New York University School of Medicine
New York, New York, 10016
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Dose and Pharmacodynamic Efficacy of Sialic Acid-Extended Release (SA-ER) Tablets in Patients With GNE Myopathy or Hereditary Inclusion Body Myopathy
GNE myopathy or hereditary inclusion body myopathy (HIBM) is a severe progressive metabolic myopathy caused by a defect in the biosynthetic pathway for sialic acid (SA).
Read the detailed description
GNE myopathy or hereditary inclusion body myopathy (HIBM) is a severe progressive metabolic myopathy caused by a defect in the biosynthetic pathway for sialic acid (SA). Substrate replacement therapy is a potential therapeutic strategy based on the success of replacing missing SA and reducing muscle disease in a relevant mouse model of the human disease (Malicdan et al., 2009). Successful use of SA replacement therapy in humans is believed to depend upon providing steady long-term exposure to the compound in an extended release form (such as Sialic Acid-Extended Release [SA-ER]), given SA's short half-life. Following a Phase 1 study to establish the pharmacokinetics (PK) for SA-ER, Ultragenyx is conducting this study to assess the dose and potential pharmacodynamic effect of restoring sialylation of muscle by treatment with SA-ER at two dose levels as compared to placebo when administered over two 24 week periods of time. The study will also evaluate safety, as well as the effect of SA-ER on clinical measures of muscle strength, mobility, function and self-reported disability and quality of life. Effects on muscle volume/mass and function and on serum biomarkers will be evaluated as exploratory measures. These data should allow the selection of a dose and the appropriate design for a Phase 3 clinical study.
- Conditions
- GNE Myopathy, Hereditary Inclusion Body Myopathy
- Being tested
- Sialic Acid Extended Release (SA-ER), Placebo
- Keywords
- Hereditary Inclusion Body Myopathy (HIBM), GNE myopathies, distal myopathy with rimmed vacuoles [DMRV], Nonaka disease
- Medical subject headings
- Distal myopathy, Nonaka type
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sialic Acid Extended Release (SA-ER)Drug
SA-ER will be administered in doses of 3000mg per day or 6000mg per day
PlaceboDrug
Subjects will be randomized to the placebo arm for the first 24 weeks of the study. Then, subjects in this arm will be re-randomized into either the 3,000 mg per day or 6,000 mg per day arm for the remaining 24 weeks of the study (total study duration 48 weeks).
| Study group | Role | What they receive |
|---|---|---|
| 6,000 mg SA-ER | Experimental | Subjects will receive this dose for the duration of the study (total study duration of 48 weeks). Receives: Drug: Sialic Acid Extended Release (SA-ER) |
| Placebo | Placebo comparator | Subjects will be randomized to the placebo arm for the first 24 weeks of the study. Then, subjects in this arm will be re-randomized into either the 3,000 mg per day or 6,000 mg per day arm for the remaining 24 weeks of the study (48 weeks total study duration). Receives: Drug: Placebo |
| 3,000 mg SA-ER | Experimental | Subjects will receive this dose for the duration of the study (total study duration of 48 weeks). Receives: Drug: Sialic Acid Extended Release (SA-ER) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the effect of SA-ER treatment on muscle sialylation, strength, and function in patients with HIBM.
To evaluate the effect of SA-ER treatment on improvement of biochemical measures of sialylation and pathology in muscle. On mobility, strength, and function using a series of quantitative and physical performance measures and quality of life using patient-reported outcome measures.
Measured: Baseline, Week 24, and Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2012 (estimated)
- Study startMay 2012
- Primary completionNov 2013
- Study completionNov 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GNE MyopathyStudies of the same condition, open and under way.
- More trials run by Ultragenyx Pharmaceutical IncThe sponsor's other registered studies.
- 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ultragenyx Pharmaceutical Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alan Pestronk, MD, Principal investigator, Washington University School of MedicinePerry Shieh, MD, Principal investigator, University of California, Los AngelesYoseph Caraco, MD, Principal investigator, Hadassah University HospitalHeather Lau, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01517880
- Sponsor's protocol ID
- UX001-CL201
- Acronym
- GNE Myopathy
- Status last verified
- Jun 2016
- First submitted
- 17 Jan 2012
- Last updated
- 16 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Dose and Pharmacodynamic Efficacy of Sialic Acid-Extended Release (SA-ER) Tablets in Patients With GNE Myopathy or Hereditary Inclusion Body Myopathy
- ClinicalTrials.gov ID
- NCT01517880
- Acronym / sponsor ID
- GNE Myopathy / UX001-CL201
- Conditions
- GNE Myopathy, Hereditary Inclusion Body Myopathy
- Keywords
- Hereditary Inclusion Body Myopathy (HIBM), GNE myopathies, distal myopathy with rimmed vacuoles [DMRV], Nonaka disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Ultragenyx Pharmaceutical IncIndustry (pharma, biotech, devices)
- Study start
- May 2012
- Primary completion
- Nov 2013 (actual)
- Study completion
- Nov 2013 (actual)
- First posted
- 25 Jan 2012 (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.
GNE myopathy or hereditary inclusion body myopathy (HIBM) is a severe progressive metabolic myopathy caused by a defect in the biosynthetic pathway for sialic acid (SA).
Detailed description
GNE myopathy or hereditary inclusion body myopathy (HIBM) is a severe progressive metabolic myopathy caused by a defect in the biosynthetic pathway for sialic acid (SA). Substrate replacement therapy is a potential therapeutic strategy based on the success of replacing missing SA and reducing muscle disease in a relevant mouse model of the human disease (Malicdan et al., 2009). Successful use of SA replacement therapy in humans is believed to depend upon providing steady long-term exposure to the compound in an extended release form (such as Sialic Acid-Extended Release [SA-ER]), given SA's short half-life. Following a Phase 1 study to establish the pharmacokinetics (PK) for SA-ER, Ultragenyx is conducting this study to assess the dose and potential pharmacodynamic effect of restoring sialylation of muscle by treatment with SA-ER at two dose levels as compared to placebo when administered over two 24 week periods of time. The study will also evaluate safety, as well as the effect of SA-ER on clinical measures of muscle strength, mobility, function and self-reported disability and quality of life. Effects on muscle volume/mass and function and on serum biomarkers will be evaluated as exploratory measures. These data should allow the selection of a dose and the appropriate design for a Phase 3 clinical study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 6,000 mg SA-ER | Experimental | Drug: Sialic Acid Extended Release (SA-ER)Subjects will receive this dose for the duration of the study (total study duration of 48 weeks). |
| Placebo | Placebo comparator | Drug: PlaceboSubjects will be randomized to the placebo arm for the first 24 weeks of the study. Then, subjects in this arm will be re-randomized into either the 3,000 mg per day or 6,000 mg per day arm for the remaining 24 weeks of the study (48 weeks total study duration). |
| 3,000 mg SA-ER | Experimental | Drug: Sialic Acid Extended Release (SA-ER)Subjects will receive this dose for the duration of the study (total study duration of 48 weeks). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Must be between 18 and 65 years of age, inclusive.
- Must be willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures.
- Must have a documented diagnosis of GNE myopathy, HIBM, distal myopathy with rimmed vacuoles (DMRV), or Nonaka disease due to previously demonstrated mutations in the gene encoding the GNE/MNK enzyme. Genotyping will not be conducted in this protocol.
- Must be able to walk 20 meters independently (may use orthotics and assistive devices).
- Must be able to provide reproducible force in bilateral elbow flexors and knee extensors during hand-held dynamometry testing (unilateral between test variability of < 15% for both muscle groups).
Key exclusion criteria (7 listed)
- Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
- Use of any investigational product or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
- Ingestion of N-acetyl-D-mannosamine (ManNAc), SA, or related metabolites; intravenous immune globulin (IVIG); or anything that can be metabolized to produce SA in the body for the prior 60 days.
- Has a condition of such severity and acuity, in the opinion of the investigator, that it warrants immediate surgical intervention or other treatment or may not allow safe participation in the study.
- Has had any hypersensitivity to SA or its excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects.
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 |
|---|---|---|
| Sialic Acid Extended Release (SA-ER)SA-ER will be administered in doses of 3000mg per day or 6000mg per day | Drug | 3,000 mg SA-ER, 6,000 mg SA-ER |
| PlaceboSubjects will be randomized to the placebo arm for the first 24 weeks of the study. Then, subjects in this arm will be re-randomized into either the 3,000 mg per day or 6,000 mg per day arm for the remaining 24 weeks of the study (total study duration 48 weeks). | Drug | Placebo |
Primary outcome
Evaluate the effect of SA-ER treatment on muscle sialylation, strength, and function in patients with HIBM.
Time frame: Baseline, Week 24, and Week 48
To evaluate the effect of SA-ER treatment on improvement of biochemical measures of sialylation and pathology in muscle. On mobility, strength, and function using a series of quantitative and physical performance measures and quality of life using patient-reported outcome measures.
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 16 Jun 2016.
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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.
Alan Pestronk, MD principal investigator
Washington University School of Medicine
Perry Shieh, MD principal investigator
University of California, Los Angeles
Yoseph Caraco, MD principal investigator
Hadassah University Hospital
4 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 Sialic Acid Extended Release (SA-ER) in people with GNE Myopathy and Hereditary Inclusion Body Myopathy, run by Ultragenyx Pharmaceutical Inc at 4 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 8 inclusion and 7 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 16 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Israel. 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. Some participants in this study may receive a placebo. 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.
What does the primary outcome measure?
Evaluate the effect of SA-ER treatment on muscle sialylation, strength, and function in patients with HIBM. (time frame: Baseline, Week 24, and Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Jun 2016.