Clinical trial NCT02736188: 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)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hereditary Inclusion Body Myopathy
Distal Myopathy With Rimmed Vacuoles
Distal Myopathy, Nonaka Type
GNE Myopathy
Quadriceps Sparing Myopathy
Keywords: GNE Myopathy
GNEM
Nonaka
Hereditary Inclusion Body Myopathy
HIBM
DMRV
QSM
Lead sponsor: Ultragenyx Pharmaceutical Inc
Sponsor class: INDUSTRY
First posted: 2016-04-13
Enrollment: 143
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The objective of this study is to evaluate the long-term safety and efficacy of Ace-ER treatment in subjects with GNEM.

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).

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

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

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious AEs (SAEs), and Discontinuations Due to AEs
timeFrame: 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.
measure: Change From Baseline in HHD UEC Score Over Time
timeFrame: Baseline, Weeks 8, 16, 24, 48
Secondary outcomes:
measure: Change From Baseline in the GNEM-FAS Expanded Version Mobility Domain Score Over Time
timeFrame: Baseline, Weeks 8, 16, 24, 48
measure: Change From Baseline on the GNEM-FAS Upper Extremity Domain Score Over Time
timeFrame: Baseline, Weeks 8, 16, 24, 48
measure: Change From Baseline in HHD Lower Extremity Composite (LEC) Score Over Time
timeFrame: Baseline, Weeks 8, 16, 24, and 48
measure: Change From Baseline in the Number of Stands in the Sit-to-Stand Test Over Time
timeFrame: Baseline, Weeks 8, 16, 24, and 48
measure: Change From Baseline in Number of Lifts in the 30-Second Weighted Arm Lift Test Over Time
timeFrame: Baseline, Weeks 8, 16, 24, and 48
measure: Change From Baseline in Meters Walked in 6MWT Over Time
timeFrame: Baseline, Weeks 8, 16, 24, and 48
measure: Change From Baseline in Percent Predicted Meters Walked in 6MWT Over Time
timeFrame: Baseline, Weeks 8, 16, 24, and 48
measure: Change From Baseline in Total Force in Knee Extensors Over Time
timeFrame: Baseline, Weeks 8, 16, 24, and 48
measure: Change From Baseline in Percent Predicted Total Force in Knee Extensors Over Time
timeFrame: Baseline, Weeks 8, 16, 24, and 48
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Orange
country: United States
facility: University of California, Irvine
state: California
city: Saint Louis
country: United States
facility: Washington University School of Medicine, St. Louis
state: Missouri
city: New York
country: United States
facility: New York University School of Medicine
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Sofia
country: Bulgaria
facility: UMHAT Alexandrovska, Bulgaria
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: Saint-Pierre
country: France
facility: CHU La Réunion - site GHSR
state: Reunion
city: Paris
country: France
facility: Institut de Myologie GH Pitié-Salpêtrière
city: Jerusalem
country: Israel
facility: Hadassah-Hebrew University Medical Center
city: Messina
country: Italy
facility: University of Messina
city: Milan
country: Italy
facility: University of Milan
city: Rome
country: Italy
facility: Università Cattolica
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle upon Tyne Hospitals
state: Tyne And Wear
Study officials:
affiliation: Ultragenyx Pharmaceutical Inc
name: Medical Director
role: STUDY_DIRECTOR
References: