Hereditary Inclusion Body MyopathyPhase 3NCT02736188
Study to Evaluate the Safety and Efficacy of Aceneuramic Acid Extended-Release (Ace-ER) Tablets 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 Tablets in people with Hereditary Inclusion Body Myopathy and Distal Myopathy With Rimmed Vacuoles, run by Ultragenyx Pharmaceutical Inc at 14 sites in 7 countries.
Trial summary
The objective of this study is to evaluate the long-term safety and efficacy of Ace-ER treatment in subjects with GNEM. Read more about this study
- Who is it for?
- Ages 18 years and older
- 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 Tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 143 participants
- Where
- 14 sitesin 7 countries
- Study dates
- 2 May 2016to 10 Jan 2018
- Phase
- Phase 3
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have completed UX001-CL202, UX001-CL301 or UX001-CL203 study
- 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
- Willing to comply with all study procedures
- Female participants of child-bearing potential or male participants with female 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 30 days 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
- Individuals who meet any of the following exclusion criteria will not be eligible to participate in the study:
- Ingestion of N-acetyl-D-mannosamine (ManNAc) 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
- Has had any hypersensitivity to sialic acid (SA) or its excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects
- 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
14 sites in 7 countries.
14 sites in 7 countries
United States5 sites
UCLA
Los Angeles, California, 90095
New York University School of Medicine
New York, New York, 10016
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
University of California, Irvine
Orange, California, 92868
Washington University School of Medicine, St. Louis
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: Phase 3B Open-Label Extension Study to Evaluate the Safety and Efficacy of Aceneuramic Acid Extended-Release (Ace-ER) Tablets in Patients With GNE Myopathy (GNEM) or Hereditary Inclusion Body Myopathy (HIBM)
The objective of this study is to evaluate the long-term safety and efficacy of Ace-ER treatment in subjects with GNEM.
Read the detailed description
This Phase 3b extension study will assess the long-term safety of Ace-ER in patients who participated in and completed study UX001-CL301 (NCT02377921), study UX001-CL202 (NCT01830972), and study UX001-CL203 (NCT02731690).
- Conditions
- Hereditary Inclusion Body Myopathy, Distal Myopathy With Rimmed Vacuoles, Distal Myopathy, Nonaka Type, GNE Myopathy, Quadriceps Sparing Myopathy
- Being tested
- Aceneuramic Acid Extended-Release Tablets
- Keywords
- GNE Myopathy, GNEM, Nonaka, Hereditary Inclusion Body Myopathy, HIBM, DMRV, QSM
- 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 TabletsDrug
Also called UX001, Sialic Acid Extended Release, Ace-ER
| Study group | Role | What they receive |
|---|---|---|
| Drug: Aceneuramic Acid Extended-Release Tablets | Experimental | Participants will take 4 tablets (500 mg Ace-ER each for 2 g per dose) orally 3 times per day (TID). Receives: Drug: Aceneuramic Acid Extended-Release Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs (SAEs), and Discontinuations Due to AEs
An AE was defined as any untoward medical occurrence associated with the use of a drug, whether or not considered drug related. An SAE or serious suspected adverse reaction is an AE or suspected adverse reaction that at any dose, in the view of either the Investigator or Ultragenyx, results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or disability (substantial disruption of the ability to conduct normal life functions); congenital anomaly/birth defect. TEAEs were defined as any AE that occurred after the first dose of study drug. The severity of all AEs were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03: grade1=mild, grade 2=moderate, grade 3=severe, grade 4=life-threatening, grade 5=death.
Measured: From first dose of study drug through the end of treatment plus 30 days (+5 days). Mean (SD) duration of treatment was 256.3 (101.54) days.
Change From Baseline in HHD UEC Score Over Time
Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. The UEC is derived from the sum of the average of the right and left total force (measured in kgf). Analyzed using a repeated measure generalized estimation equation (GEE) model, which includes the baseline value as a covariate.
Measured: Baseline, Weeks 8, 16, 24, 48
Secondary outcomes (9)
Change From Baseline in the GNEM-FAS Expanded Version Mobility Domain Score Over Time
GNEM-FAS Expanded Version Mobility subscale score has 13 items and ranges from 0 to 52 with higher scores representing greater mobility. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Measured: Baseline, Weeks 8, 16, 24, 48
Change From Baseline on the GNEM-FAS Upper Extremity Domain Score Over Time
GNEM-FAS Expanded Version Upper Extremity subscale score has 9 items and ranges from 0 to 36 with higher scores representing more skilled, independent use of the arms during functional activity performance. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Measured: Baseline, Weeks 8, 16, 24, 48
Change From Baseline in HHD Lower Extremity Composite (LEC) Score Over Time
Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. The LEC is derived from the sum of the average of the right and left total force (measured in kgf). Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Measured: Baseline, Weeks 8, 16, 24, and 48
Change From Baseline in the Number of Stands in the Sit-to-Stand Test Over Time
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. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Measured: Baseline, Weeks 8, 16, 24, and 48
Change From Baseline in Number of Lifts in the 30-Second Weighted Arm Lift Test Over Time
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. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Measured: Baseline, Weeks 8, 16, 24, and 48
Change From Baseline in Meters Walked in 6MWT Over Time
The total distance walked (meters) in a 6-minute period was measured. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Measured: Baseline, Weeks 8, 16, 24, and 48
Change From Baseline in Percent Predicted Meters Walked in 6MWT Over Time
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. Predicted 6MWT distance (meters) = 868.8 - (2.99 x Age) - (74.7 x Sex), where age is baseline age in years, and sex = 0 for males, and 1 for females. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Measured: Baseline, Weeks 8, 16, 24, and 48
Change From Baseline in Total Force in Knee Extensors Over Time
Hand held dynamometry testing was used to measure strength. The maximum voluntary isometric contraction against a dynamometer was used to measure bilateral strength in the following muscle groups: shoulder abductors, wrist extensors and knee extensors. Specialized dynamometers for the measurement of grip and key pinch strength were also used. The total force (in kgf) for each was recorded. Bilateral total force was defined as the average of the right and left force (measured in kgf). Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Measured: Baseline, Weeks 8, 16, 24, and 48
Change From Baseline in Percent Predicted Total Force in Knee Extensors Over Time
The percent predicted total force value of lower extremity muscle strength in the knee extensors was determined based on reference equations adjusting for age, gender, height, and weight. Analyzed using a repeated measure GEE model, which includes the baseline value as a covariate.
Measured: Baseline, Weeks 8, 16, 24, and 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2016 (estimated)
- Study start2 May 2016
- Primary completion10 Jan 2018
- Study completion10 Jan 2018
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.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 143 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ultragenyx Pharmaceutical Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Ultragenyx Pharmaceutical Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02736188
- Sponsor's protocol ID
- UX001-CL302
- Status last verified
- Mar 2023
- First submitted
- 4 Apr 2016
- Last updated
- 24 Mar 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No