A study to see if Aceneuramic Acid is safe in treating people with GNE Myopathy (GNEM) patients (a rare muscle disease also known as Hereditary Inclusion Body Myopathy (HIBM)) with severe ambulatory impairment.

• Register: EUCTR
• Last refreshed on: 5 February 2018
• Main ID: EUCTR2015-004553-41-BG
• Date of registration: 14/09/2016
• Prospective Registration: Yes
• Primary sponsor: Ultragenyx Pharmaceutical Inc.
• Public title: A study to see if Aceneuramic Acid is safe in treating people with GNE Myopathy (GNEM) patients (a rare muscle disease also known as Hereditary Inclusion Body Myopathy (HIBM)) 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: 05/01/2017
• Target sample size: 45
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004553-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Canada, United States

Contacts

• Name: Clinical Operations
• Affiliation: Ultragenyx Pharmaceutical Inc.

• Name: Clinical Operations
• Affiliation: Ultragenyx Pharmaceutical Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female, aged = 18 years old
2. 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
3. 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/MNK enzyme (genotyping will not be conducted in this study).
4. 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 6MWT course)
AND
• Use of wheelchair or scooter for activities outside of the home or unable to leave the home independently
5. Willing and able to comply with all study procedures
6. Participants of childbearing potential or with partners of childbearing potential who have not undergone a bilateral salpingooophorectomy 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 doublebarrier 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
7. 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 salpingooophorectomy
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 43
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 2

Exclusion criteria:
1. 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
2. Prior participation in a clinical trial involving treatment with Ace-ER/placebo and/or Sialic Acidimmediate release (SA-IR) in the past year
3. 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
4. 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
5. Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study
6. 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
7. 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
8. 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:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

GNE Myopathy, also known as Hereditary Inclusion Body Myopathy (HIBM), Distal Myopathy with Rimmed Vacuoles (DMRV), Nonaka’s disease, or quadriceps sparing myopathy (QSM)
MedDRA version: 20.0 Level: LLT Classification code 10075048 Term: Hereditary inclusion body myopathy System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 20.0 Level: PT Classification code 10077945 Term: GNE myopathy System Organ Class: 10010331 - Congenital, familial and genetic disorders

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Name: Sialic acid (INN: aceneuramic acid)
Product Code: UX001
Pharmaceutical Form: Tablet
INN or Proposed INN: ACENEURAMIC ACID
CAS Number: 131-48-6
Current Sponsor code: UX001
Other descriptive name: sialic acid; N-acetylneuraminic acid
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Secondary Objective: Secondary Objectives: Evaluate the efficacy of 6 g/day Ace-ER in GNEM subjects with severe ambulatory impairment

Exploratory Objectives: Evaluate the effect on 6g/day Ace-ER on health-related quality of life (HRQoL), patient reported outcomes (PRO), and biomarkers of sialyation.

Primary end point(s): The primary endpoint of the study is the incidence and frequency of adverse events (AEs) and serious adverse events (SAEs) assessed as related to Ace-ER over the duration of the study.

Timepoint(s) of evaluation of this end point: Baseline, Week 12, Week 24, Week 36, Week 48.

Main Objective: Evaluate the safety of Ace-ER in GNEM subjects with severe ambulatory
impairment

Secondary Outcome(s)

Secondary end point(s): Safety Endpoints:
• Clinically significant changes from baseline to scheduled time points in concomitant medications, physical examination results, vital signs, clinical laboratory results and interval history during the course of the study

Clinical Endpoints:
• Change in GNEM-FAS Expanded Version total score and mobility, upper extremity and self-care domain scores from baseline over the duration of the study
• Change in upper extremity strength in grip, key pinch, shoulder abductors and wrist extensors as measured by dynamometry over the duration of study
• Change in lower extremity muscle strength in the knee extensors as measured by dynamometry over the duration of the study

Exploratory Endpoints:
The exploratory endpoints of the study include HRQoL, patient reported outcomes and biomarker analyses.
• Change in health-related quality of life as assessed by using Short Form Health Survey -36 (SF-36) over the duration of the study
• Change in symptom severity as measured by Patient Global Impression of Severity (PGI-S) and Patient Global Impression of Change (PGI-C) over the duration of the study
• Changes in serum creatine kinase (CK) as a marker of muscle injury over the duration of the study
• Changes in biomarkers of sialylation

Timepoint(s) of evaluation of this end point: The secondary safety endpoints will be assessed at visits Baseline, Week 12, Week 24, Week 36, Week 48..

The clinical endpoints will be assessed at baseline, week visits 12, 24, 36, 48.

The exploratory endpoints will be assessed at visits baseline, 12, 24, 36, 48.

Secondary ID(s)

UX001-CL203

NCT02731690

Source(s) of Monetary Support

Ultragenyx Pharmaceutical Inc.