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)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02377921
• Date of registration: 27/02/2015
• Prospective Registration: Yes
• Primary sponsor: Ultragenyx Pharmaceutical Inc
• Public title: 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) GNEM
• Scientific 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)
• Date of first enrolment: May 20, 2015
• Target sample size: 89
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02377921
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Bulgaria, Canada, France, Israel, Italy, United Kingdom, United States

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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



Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Distal Myopathy With Rimmed Vacuoles

Distal Myopathy, Nonaka Type

Hereditary Inclusion Body Myopathy

GNE Myopathy

Intervention(s)

Drug: Placebo

Drug: aceneuramic acid extended-release (Ace-ER)

Primary Outcome(s)

Change From Baseline in UEC Score (Total Force in kg) at Week 48 [Time Frame: Baseline, Week 48]

Secondary Outcome(s)

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 GNEM FAS Upper Extremity Domain Score 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 Number of Stands in the Sit to Stand Test at Week 48 [Time Frame: Baseline, Week 48]

Change From Baseline in Muscle Strength in the Knee Extensors 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]

Secondary ID(s)

UX001-CL301

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 09/07/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02377921