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)

NCT02377921 | Completed Phase 3 Results DMC

• 1 other identifier: UX001-CL301
• Study Type: interventional
• Target: 89
• Locations: 7 countries
• Sites: 13

Brief Summary

The primary objective of this study is to evaluate the effect of 6 g/day aceneuramic acid extended-release (Ace-ER) treatment of participants with GNEM on upper extremity muscle strength (upper extremity composite \[UEC\] score) as measured by dynamometry.

Conditions

Hereditary Inclusion Body Myopathy; Distal Myopathy With Rimmed Vacuoles; Distal Myopathy, Nonaka Type; GNE Myopathy

Keywords

GNE Myopathy; GNEM; HIBM; Nonaka; Hereditary Inclusion Body Myopathy; DMRV

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in UEC Score (Total Force in kg) at Week 48

  Muscle strength based on the maximum voluntary isometric contraction (MVIC) against a dynamometer was measured bilaterally in the following upper extremity muscle groups: gross grip, shoulder abductors, elbow flexors, and elbow extensors. The UEC is derived from the sum of the average of the right and left total force values (measured in kg).

  Baseline, Week 48

Secondary Outcomes (8)

• Change From Baseline in Muscle Strength in the Knee Extensors at Week 48

  Baseline, Week 48

• Change From Baseline in LEC Score (Total Force in kg) at Week 48

  Baseline, Week 48

• Change From Baseline in GNEM FAS Mobility Domain Score at Week 48

  Baseline, Week 48

• Change From Baseline in Number of Lifts in the 30 Second Weighted Arm Lift Test at Week 48

  Baseline, Week 48

• Change From Baseline in Number of Stands in the Sit to Stand Test at Week 48

  Baseline, Week 48

Study Arms (2)

Aceneuramic Acid Extended-Release (Ace-ER)

EXPERIMENTAL

Ace-ER 6 g/day, divided 3 times per day (TID) for 48 weeks.

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

Placebo

PLACEBO COMPARATOR

Matching placebo TID for 48 weeks.

Drug: Placebo

Interventions

aceneuramic acid extended-release (Ace-ER) DRUG

tablets for oral use

Also known as: UX001, sialic acid extended-release (SA-ER)

Aceneuramic Acid Extended-Release (Ace-ER)

Placebo DRUG

tablets for oral use

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead

Study Sites (13)

University of California, Irvine

Irvine, California, 92697, United States

Location

Washington University School of Medicine

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"

Sofia, Bulgaria

Location

McMaster University

Hamilton, Ontario, L8N3Z5, 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

Related Publications (2)

• Lochmuller H, Behin A, Caraco Y, Lau H, Mirabella M, Tournev I, Tarnopolsky M, Pogoryelova O, Woods C, Lai A, Shah J, Koutsoukos T, Skrinar A, Mansbach H, Kakkis E, Mozaffar T. A phase 3 randomized study evaluating sialic acid extended-release for GNE myopathy. Neurology. 2019 Apr 30;92(18):e2109-e2117. doi: 10.1212/WNL.0000000000006932. Epub 2019 Jan 25.

  PMID: 31036580 RESULT

• Tandon PK, Kakkis ED. The multi-domain responder index: a novel analysis tool to capture a broader assessment of clinical benefit in heterogeneous complex rare diseases. Orphanet J Rare Dis. 2021 Apr 19;16(1):183. doi: 10.1186/s13023-021-01805-5.

  PMID: 33874971 DERIVED

MeSH Terms

Conditions

Distal myopathy, Nonaka type

Results Point of Contact

• Title: Medical Information
• Organization: Ultragenyx Pharmaceutical Inc

medinfo@ultragenyx.com

1-888-756-8567

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2015
• First Posted: March 4, 2015
• Study Start: May 20, 2015
• Primary Completion: June 9, 2017
• Study Completion: June 9, 2017
• Last Updated: June 27, 2019
• Results First Posted: July 9, 2018

Record last verified: 2019-06

Locations

CA (1); IT (3); US (4); IL (1); GB (1); FR (2); BU (1)