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)

NCT02736188 | Terminated Phase 3 Results

• 1 other identifier: UX001-CL302
• Study Type: interventional
• Target: 143
• Locations: 7 countries
• Sites: 14

Brief Summary

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

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Baseline, Weeks 8, 16, 24, 48

Secondary Outcomes (9)

• Change From Baseline in the GNEM-FAS Expanded Version Mobility Domain Score Over Time

  Baseline, Weeks 8, 16, 24, 48

• Change From Baseline on the GNEM-FAS Upper Extremity Domain Score Over Time

  Baseline, Weeks 8, 16, 24, 48

• Change From Baseline in HHD Lower Extremity Composite (LEC) Score Over Time

  Baseline, Weeks 8, 16, 24, and 48

• Change From Baseline in the Number of Stands in the Sit-to-Stand Test Over Time

  Baseline, Weeks 8, 16, 24, and 48

• Change From Baseline in Number of Lifts in the 30-Second Weighted Arm Lift Test Over Time

  Baseline, Weeks 8, 16, 24, and 48

Study Arms (1)

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).

Drug: Aceneuramic Acid Extended-Release Tablets

Interventions

Aceneuramic Acid Extended-Release Tablets DRUG

Also known as: UX001, Sialic Acid Extended Release, Ace-ER

Drug: Aceneuramic Acid Extended-Release Tablets

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead

Study Sites (14)

UCLA

Los Angeles, California, 90095, United States

Location

University of California, Irvine

Orange, California, 92868, United States

Location

Washington University School of Medicine, St. Louis

St Louis, Missouri, 63110, United States

Location

New York University School of Medicine

New York, New York, 10016, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

UMHAT Alexandrovska, Bulgaria

Sofia, 1431, Bulgaria

Location

McMaster University

Hamilton, Ontario, L8N 3Z5, Canada

Location

CHU La Réunion - site GHSR

Saint-Pierre, Reunion, France

Location

Institut de Myologie GH Pitié-Salpêtrière

Paris, France

Location

Hadassah-Hebrew University Medical Center

Jerusalem, Israel

Location

University of Messina

Messina, Italy

Location

University of Milan

Milan, Italy

Location

Università Cattolica

Rome, Italy

Location

The Newcastle upon Tyne Hospitals

Newcastle upon Tyne, Tyne and Wear, NE1 4LP, United Kingdom

Location

MeSH Terms

Conditions

Distal myopathy, Nonaka type

Limitations and Caveats

No efficacy result summaries or analyses were performed for participants rolling over from UX001-CL202 or UX001-CL203 because of the limited data from those participants due to the early study closure.

Results Point of Contact

• Title: Medical Information
• Organization: Ultragenyx Pharmaceutical Inc

medinfo@ultragenyx.com

1-888-756-8657

Study Officials

• Medical Director

  Ultragenyx Pharmaceutical Inc

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 4, 2016
• First Posted: April 13, 2016
• Study Start: May 2, 2016
• Primary Completion: January 10, 2018
• Study Completion: January 10, 2018
• Last Updated: March 24, 2023
• Results First Posted: February 19, 2019

Record last verified: 2023-03

Locations

CA (1); BU (1); IL (1); GB (1); FR (2); US (5); IT (3)