Hereditary Inclusion Body MyopathyPhase 3GNEMNCT02377921
Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Sialic Acid in Patients With Glucosamine (UDP-N-acetyl)-2-epimerase Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM)
A Phase 3 study testing aceneuramic acid extended-release (Ace-ER) in people with Hereditary Inclusion Body Myopathy and Distal Myopathy With Rimmed Vacuoles, run by Ultragenyx Pharmaceutical Inc at 13 sites in 7 countries.
Trial summary
The primary objective of this study is to evaluate the effect of 6 g/day aceneuramic acid extended-release (Ace-ER) treatment of participants with GNEM on upper extremity muscle strength (upper extremity composite [UEC] score) as measured by dynamometry. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Hereditary Inclusion Body Myopathy, Distal Myopathy With Rimmed Vacuoles, Distal Myopathy, Nonaka Type
- What is being tested?
- aceneuramic acid extended-release (Ace-ER)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 89 participants
- Where
- 13 sitesin 7 countries
- Study dates
- 20 May 2015to 9 Jun 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Male or female, aged 18 to 55 years, inclusive
- Willing and able to provide written, signed informed consent after the nature of the study has been explained, and before any research-related procedures are conducted
- Have a documented diagnosis of GNEM, HIBM, distal myopathy with rimmed vacuoles (DMRV), or Nonaka disease due to previously demonstrated mutations in the gene encoding the GNE/N-acetylmannosamine kinase (MNK) enzyme (genotyping will not be conducted in this study)
- Able to provide reproducible force in elbow flexors (i.e. two dynamometry force values with no more than 15% variability in the dominant arm) at Screening
- Able to walk a minimum of 200 meters during the six-meter walk test (6MWT) at Screening without the use of assistive devices, including a cane, crutch(es), walker, wheelchair or scooter (ankle foot orthosis/orthoses are permitted)
- Willing and able to comply with all study procedures
- Participants of child-bearing potential or with partners of child-bearing potential who have not undergone a bilateral salpingo-oophorectomy and are sexually active must consent to use a highly effective method of contraception as determined by the site investigator (i.e. oral hormonal contraceptives, patch hormonal contraceptives, vaginal ring, intrauterine device, physical double-barrier methods, surgical hysterectomy, vasectomy, tubal ligation, or true abstinence [when this is in line with the preferred and usual lifestyle of the subject], which means not having sex because the subject chooses not to), from the period following the signing of the informed consent through 3 months after last dose of study drug
- 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, have had tubal ligation at least one year prior to Screening, or who have had a total hysterectomy or bilateral salpingo-oophorectomy
Who cannot join
- Ingestion of N-acetyl-D-mannosamine (ManNAc), sialic acid (SA), or related metabolites; intravenous immunoglobulin (IVIG); or anything that can be metabolized to produce SA in the body within 60 days prior to the Screening Visit
- History of more than 30 days treatment with SA-ER and/or Sialic Acid Immediate Release (SA-IR) in prior clinical trials in the past year
- 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 serum transaminase (i.e. aspartate aminotransferase [AST] or gamma-glutamyl transpeptidase [GGT]) levels greater than 3X the upper limit of normal (ULN) for age/gender, or serum creatinine of greater than 2X ULN at Screening
- 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 anticipated requirement for any investigational agent prior to completion of all scheduled study assessments
- 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 a concurrent disease, active suicidal ideation, or other condition that, in the view of the 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
Trial locations and contacts
13 sites in 7 countries.
13 sites in 7 countries
United States4 sites
University of California, Irvine
Irvine, California, 92697
New York University School of Medicine
New York, New York, 10016
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Washington University School of Medicine
St Louis, Missouri, 63110
Italy3 sites
University of Messina
Messina
University of Milan
Milan
Università Cattolica
Rome
France2 sites
Institut de Myologie GH Pitié-Salpêtrière
Paris
CHU La Réunion - site GHSR
Saint-Pierre, Reunion
United Kingdom1 site
The Newcastle upon Tyne Hospitals
Newcastle upon Tyne, Tyne and Wear, NE1 4LP
About this study
Official title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Sialic Acid Extended-Release Tablets in Patients With GNE Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM)
The primary objective of this study is to evaluate the effect of 6 g/day aceneuramic acid extended-release (Ace-ER) treatment of participants with GNEM on upper extremity muscle strength (upper extremity composite [UEC] score) as measured by dynamometry.
- Conditions
- Hereditary Inclusion Body Myopathy, Distal Myopathy With Rimmed Vacuoles, Distal Myopathy, Nonaka Type, GNE Myopathy
- Being tested
- aceneuramic acid extended-release (Ace-ER), Placebo
- Keywords
- GNE Myopathy, GNEM, HIBM, Nonaka, Hereditary Inclusion Body Myopathy, DMRV
- 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.
aceneuramic acid extended-release (Ace-ER)Drug
Also called UX001, sialic acid extended-release (SA-ER)
tablets for oral use
PlaceboDrug
tablets for oral use
| Study group | Role | What they receive |
|---|---|---|
| Aceneuramic Acid Extended-Release (Ace-ER) | Experimental | Ace-ER 6 g/day, divided 3 times per day (TID) for 48 weeks. Receives: Drug: aceneuramic acid extended-release (Ace-ER) |
| Placebo | Placebo comparator | Matching placebo TID for 48 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in UEC Score (Total Force in kg) at Week 48
Muscle strength based on the maximum voluntary isometric contraction (MVIC) against a dynamometer was measured bilaterally in the following upper extremity muscle groups: gross grip, shoulder abductors, elbow flexors, and elbow extensors. The UEC is derived from the sum of the average of the right and left total force values (measured in kg).
Measured: Baseline, Week 48
Secondary outcomes (8)
Change From Baseline in Muscle Strength in the Knee Extensors at Week 48
Lower extremity muscle strength in the knee extensors was measured by dynamometry. Bilateral total force was defined as the average of the right and left force values (measured in kg).
Measured: Baseline, Week 48
Change From Baseline in LEC Score (Total Force in kg) at Week 48
Muscle strength based on MVIC against a dynamometer was measured bilaterally in the following lower extremity muscle groups: knee flexors, hip flexors, hip extensors, hip abductors and hip adductors. The LEC is derived from the sum of the average of the right and left total force values (measured in kg).
Measured: Baseline, Week 48
Change From Baseline in GNEM FAS Mobility Domain Score at Week 48
Lower extremity use and function was assessed using the Mobility domain of the GNEM-FAS instrument a disease-specific measure developed to assess the functional impact of changes in muscle strength on mobility (reflective of the lower extremities). This mobility score ranges from 0 to 40 with higher scores representing greater mobility.
Measured: Baseline, Week 48
Change From Baseline in Number of Lifts in the 30 Second Weighted Arm Lift Test at Week 48
Upper extremity function was assessed using a weighted arm lift test performed bilaterally. The number of times the participant can raise a 1 kg weight above the head in a 30-second period was recorded.
Measured: Baseline, Week 48
Change From Baseline in Number of Stands in the Sit to Stand Test at Week 48
Lower extremity function was assessed using a sit-to-stand test. The number of times the participant can rise from a seated to a standing position in a 30-second period was recorded.
Measured: Baseline, Week 48
Change From Baseline in Meters Walked in the 6MWT at Week 48
The total distance walked (meters) in a 6-minute period was measured.
Measured: Baseline, Week 48
Change From Baseline in Percent Predicted Meters Walked in the 6MWT at Week 48
The total distance walked (meters) in a 6-minute period was measured, and the percent predicted distance based on normative data for age and gender was estimated.
Measured: Baseline, Week 48
Change From Baseline in GNEM FAS Upper Extremity Domain Score at Week 48
Upper extremity use and function was assessed using the Mobility domain of the GNEM-FAS instrument a disease-specific measure developed to assess the functional impact of changes in muscle strength on mobility (reflective of the upper extremities). This mobility score ranges from 0 to 40 with higher scores representing greater mobility.
Measured: Baseline, Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2015 (estimated)
- Study start20 May 2015
- Primary completion9 Jun 2017
- Study completion9 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hereditary Inclusion Body 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ultragenyx Pharmaceutical Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02377921
- Sponsor's protocol ID
- UX001-CL301
- Acronym
- GNEM
- Status last verified
- Jun 2019
- First submitted
- 27 Feb 2015
- Last updated
- 27 Jun 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Lochmuller H, Behin A, Caraco Y, Lau H, Mirabella M, Tournev I, Tarnopolsky M, Pogoryelova O, Woods C, Lai A, Shah J, Koutsoukos T, Skrinar A, Mansbach H, Kakkis E, Mozaffar T. A phase 3 randomized study evaluating sialic acid extended-release for GNE myopathy. Neurology. 2019 Apr 30;92(18):e2109-e2117. doi: 10.1212/WNL.0000000000006932. Epub 2019 Jan 25.
PubMed 31036580Tandon PK, Kakkis ED. The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases. Orphanet J Rare Dis. 2021 Apr 19;16(1):183. doi: 10.1186/s13023-021-01805-5.
PubMed 33874971
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Sialic Acid Extended-Release Tablets in Patients With GNE Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM)
- ClinicalTrials.gov ID
- NCT02377921
- Acronym / sponsor ID
- GNEM / UX001-CL301
- Conditions
- Hereditary Inclusion Body Myopathy, Distal Myopathy With Rimmed Vacuoles, Distal Myopathy, Nonaka Type, GNE Myopathy
- Keywords
- GNE Myopathy, GNEM, HIBM, Nonaka, Hereditary Inclusion Body Myopathy, DMRV
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 89 participants (actual)
- Lead sponsor
- Ultragenyx Pharmaceutical IncIndustry (pharma, biotech, devices)
- Study start
- 20 May 2015 (actual)
- Primary completion
- 9 Jun 2017 (actual)
- Study completion
- 9 Jun 2017 (actual)
- First posted
- 4 Mar 2015 (estimated)
- Results
- Posted 9 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to evaluate the effect of 6 g/day aceneuramic acid extended-release (Ace-ER) treatment of participants with GNEM on upper extremity muscle strength (upper extremity composite [UEC] score) as measured by dynamometry.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aceneuramic Acid Extended-Release (Ace-ER) | Experimental | Drug: aceneuramic acid extended-release (Ace-ER)Ace-ER 6 g/day, divided 3 times per day (TID) for 48 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboMatching placebo TID for 48 weeks. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Male or female, aged 18 to 55 years, inclusive
- Willing and able to provide written, signed informed consent after the nature of the study has been explained, and before any research-related procedures are conducted
- Have a documented diagnosis of GNEM, HIBM, distal myopathy with rimmed vacuoles (DMRV), or Nonaka disease due to previously demonstrated mutations in the gene encoding the GNE/N-acetylmannosamine kinase (MNK) enzyme (genotyping will not be conducted in this study)
- Able to provide reproducible force in elbow flexors (i.e. two dynamometry force values with no more than 15% variability in the dominant arm) at Screening
- Able to walk a minimum of 200 meters during the six-meter walk test (6MWT) at Screening without the use of assistive devices, including a cane, crutch(es), walker, wheelchair or scooter (ankle foot orthosis/orthoses are permitted)
Key exclusion criteria (8 listed)
- Ingestion of N-acetyl-D-mannosamine (ManNAc), sialic acid (SA), or related metabolites; intravenous immunoglobulin (IVIG); or anything that can be metabolized to produce SA in the body within 60 days prior to the Screening Visit
- History of more than 30 days treatment with SA-ER and/or Sialic Acid Immediate Release (SA-IR) in prior clinical trials in the past year
- 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 serum transaminase (i.e. aspartate aminotransferase [AST] or gamma-glutamyl transpeptidase [GGT]) levels greater than 3X the upper limit of normal (ULN) for age/gender, or serum creatinine of greater than 2X ULN at Screening
- Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study
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 |
|---|---|---|
| aceneuramic acid extended-release (Ace-ER)Also: UX001, sialic acid extended-release (SA-ER)tablets for oral use | Drug | Aceneuramic Acid Extended-Release (Ace-ER) |
| Placebotablets for oral use | Drug | Placebo |
Primary outcome
Change From Baseline in UEC Score (Total Force in kg) at Week 48
Time frame: Baseline, Week 48
Muscle strength based on the maximum voluntary isometric contraction (MVIC) against a dynamometer was measured bilaterally in the following upper extremity muscle groups: gross grip, shoulder abductors, elbow flexors, and elbow extensors. The UEC is derived from the sum of the average of the right and left total force values (measured in kg).
8 secondary outcomes
Change From Baseline in Muscle Strength in the Knee Extensors at Week 48
Time frame: Baseline, Week 48
Change From Baseline in LEC Score (Total Force in kg) at Week 48
Time frame: Baseline, Week 48
Change From Baseline in GNEM FAS Mobility Domain Score at Week 48
Time frame: Baseline, Week 48
Change From Baseline in Number of Lifts in the 30 Second Weighted Arm Lift Test at Week 48
Time frame: Baseline, Week 48
Change From Baseline in Number of Stands in the Sit to Stand Test at Week 48
Time frame: Baseline, Week 48
Change From Baseline in Meters Walked in the 6MWT at Week 48
Time frame: Baseline, Week 48
Change From Baseline in Percent Predicted Meters Walked in the 6MWT at Week 48
Time frame: Baseline, Week 48
Change From Baseline in GNEM FAS Upper Extremity Domain Score at Week 48
Time frame: Baseline, Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31036580Lochmuller H, Behin A, Caraco Y, Lau H, Mirabella M, Tournev I, Tarnopolsky M, Pogoryelova O, Woods C, Lai A, Shah J, Koutsoukos T, Skrinar A, Mansbach H, Kakkis E, Mozaffar T. A phase 3 randomized study evaluating sialic acid extended-release for GNE myopathy. Neurology. 2019 Apr 30;92(18):e2109-e2117. doi: 10.1212/WNL.0000000000006932. Epub 2019 Jan 25.
- Derived from this study: PubMed 33874971Tandon PK, Kakkis ED. The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases. Orphanet J Rare Dis. 2021 Apr 19;16(1):183. doi: 10.1186/s13023-021-01805-5.
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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.
13 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing aceneuramic acid extended-release (Ace-ER) in people with Hereditary Inclusion Body Myopathy and Distal Myopathy With Rimmed Vacuoles, run by Ultragenyx Pharmaceutical Inc at 13 sites in 7 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 8 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 27 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Italy, France, Bulgaria, Canada and 2 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change From Baseline in UEC Score (Total Force in kg) at Week 48 (time frame: Baseline, Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02377921, which also lists 2 linked publications.
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 27 Jun 2019.