A Study to Evaluate the Safety of Aceneuramic Acid Extended Release (Ace-ER; UX001) Tablets in Glucosamine (UDP-N-acetyl)-2-Epimerase (GNE) Myopathy (GNEM) (Also Known as Hereditary Inclusion Body Myopathy [HIBM]) Patients With Severe Ambulatory Impairment

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02731690
• Date of registration: 24/03/2016
• Prospective Registration: Yes
• Primary sponsor: Ultragenyx Pharmaceutical Inc
• Public title: A Study to Evaluate the Safety of Aceneuramic Acid Extended Release (Ace-ER; UX001) Tablets in Glucosamine (UDP-N-acetyl)-2-Epimerase (GNE) Myopathy (GNEM) (Also Known as Hereditary Inclusion Body Myopathy [HIBM]) Patients With Severe Ambulatory Impairment
• Scientific title: A Phase 2 Open-label Study to Evaluate the Safety of Aceneuramic Acid Extended Release (Ace-ER) Tablets in GNE Myopathy (GNEM) (Also Known as Hereditary Inclusion Body Myopathy (HIBM)) Patients With Severe Ambulatory Impairment
• Date of first enrolment: April 29, 2016
• Target sample size: 42
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02731690
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Bulgaria, Canada, United States

Contacts

• Name: Medical Director
• Affiliation: Ultragenyx Pharmaceutical Inc

Key inclusion & exclusion criteria

Inclusion Criteria:

- Male or female, aged = 18 years old

- 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).

- Should meet the criteria for severe ambulatory impairment defined below:

- Unable to rise from a seated position to standing without help from another
person, assistive device(s), stationary object, or other support AND

- Unable to walk without the assistance of another person OR if able to walk (use
of assistive device(s) permitted), requires at least 2 minutes to walk 40 meters
(one full lap of the 6-minute walk test [6MWT] course) AND

- Use of wheelchair or scooter for activities outside of the home or unable to
leave the home independently

- 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 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

Exclusion Criteria:

- Ingestion of N-acetyl-D-mannosamine (ManNAc), 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

- Prior participation in a clinical trial involving treatment with Ace-ER/placebo and/or
Sialic Acid immediate release (SA-IR) in the past year

- Has had any hypersensitivity to aceneuramic acid 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: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Distal Myopathy With Rimmed Vacuoles

Hereditary Inclusion Body Myopathy

Quadriceps Sparing Myopathy

Distal Myopathy, Nonaka Type

GNE Myopathy

Inclusion Body Myopathy 2

Intervention(s)

Drug: Aceneuramic Acid Extended-Release

Primary Outcome(s)

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation [Time Frame: 48 Weeks (plus 30 [+5] days for participants not enrolling in extension study)]

Secondary Outcome(s)

Change From Baseline in GNEM-FAS Expanded Version Mobility Domain Subscale Scores Over Time [Time Frame: Baseline, Weeks 12, 24, 36, and 48]

Number of Participants With Clinically Significant Changes From Baseline In Physical Examinations [Time Frame: 48 weeks]

Change From Baseline in HHD Muscle Strength in Knee Extensors Over Time [Time Frame: Baseline, Weeks 12, 24, 36, and 48]

Number of Participants With Clinically Significant Changes From Baseline In Clinical Laboratory Results [Time Frame: 48 weeks]

Change From Baseline in HHD Raw Strength (Shoulder Abductors) Over Time [Time Frame: Baseline, Weeks 12, 24, 36, and 48]

Change From Baseline in GNEM-FAS Expanded Version Total Scores Over Time [Time Frame: Baseline, Weeks 12, 24, 36, and 48]

Number of Participants With Clinically Significant Changes From Baseline In Vital Signs [Time Frame: 48 weeks]

Change From Baseline in GNEM-FAS Expanded Version Self-Care Domain Subscale Scores Over Time [Time Frame: Baseline, Weeks 12, 24, 36, and 48]

Change From Baseline in GNEM-FAS Expanded Version Upper Extremity Domain Subscale Scores Over Time [Time Frame: Baseline, Weeks 12, 24, 36, and 48]

Change From Baseline in HHD Raw Strength (Grip) Over Time [Time Frame: Baseline, Weeks 12, 24, 36, and 48]

Number of Participants Taking Prior and Concomitant Medications [Time Frame: 48 weeks]

Change From Baseline in HHD Raw Strength (Key Pinch) Over Time [Time Frame: Baseline, Weeks 12, 24, 36, and 48]

Change From Baseline in HHD Raw Strength (Wrist Extensors) Over Time [Time Frame: Baseline, Weeks 12, 24, 36, and 48]

Number of Participants With Overall Suicidal Behaviors and/or Ideation at Baseline and Post-Baseline [Time Frame: 48 weeks]

Secondary ID(s)

UX001-CL203

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 19/02/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02731690