E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
GNE Myopathy, also known as Hereditary Inclusion Body Myopathy (HIBM), Distal Myopathy with Rimmed Vacuoles (DMRV), Nonaka's disease, or quadriceps sparing myopathy (QSM) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10075048 |
E.1.2 | Term | Hereditary inclusion body myopathy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10077945 |
E.1.2 | Term | GNE myopathy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Evaluate the long-term safety of Ace-ER treatment in subjects with GNE Myopathy |
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E.2.2 | Secondary objectives of the trial |
Overall Efficacy Endpoints: Evaluate the long-term effect of 6 g/day of Ace-ER treatment in subjects with GNEM. Efficacy will be evaluated as follows:
Enrolling from UX001-CL301: • Muscle strength as measured by dynamometry • Mobility, strength, and function using a series of physical performance measures • Functional disability using an patient- and clinician-reported questionnaire For Subjects Enrolling from UX001-CL203: • Change in GNEM-FAS Expanded Version total score and mobility, upper extremity and self-care domain scores • Change in upper extremity strength in grip, key pinch, shoulder abductors and wrist extensors and in lower extremity muscle strength in the knee extensors as measured by dynamometry • Evaluate the effect on 6g/day Ace-ER on health-related quality of life (HRQoL), patient reported outcomes (PRO), and biomarkers of sialyation |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Have completed the UX001-CL301 or UX001-CL203 study 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. Willing to comply with all study procedures 4. 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 5. 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 |
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E.4 | Principal exclusion criteria |
1. 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 2. 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 3. Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study 4. Use of any investigational product (except for Ace-ER/SA-ER as part of the parent study) 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 5. 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 6. 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
Overall Safety Endpoint (Primary Endpoint): Evaluate the long-term safety of 6 g/day Ace-ER treatment in subjects with GNE Myopathy |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Evaluation for all subjects at 2, 4, 6, 12, 18, and 24 Months. A safety follow-up at visit to be conducted by phone 30 days (+/- 5 days) after last dose. |
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E.5.2 | Secondary end point(s) |
Overall Efficacy Endpoint: Evaluate the long-term effect of 6 g/day of Ace-ER treatment in subjects with GNEM. Efficacy will be evaluated as follows: For Subjects Enrolling from UX001-CL301: • Muscle strength as measured by dynamometry • Mobility, strength, and function using a series of physical performance measures • Functional disability using an patient- and clinician-reported questionnaire
For Subjects Enrolling from UX001-CL203: • Change in GNEM-FAS Expanded Version total score and mobility, upper extremity and self-care domain scores • Change in upper extremity strength in grip, key pinch, shoulder abductors and wrist extensors and in lower extremity muscle strength in the knee extensors as measured by dynamometry • Evaluate the effect on 6g/day Ace-ER on health-related quality of life, patient reported outcomes (PRO), and biomarkers of sialyation |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Subjects Rolling Over from CL301 timepoints are 2, 4, 6, 12, 18, and 24 Months
Subjects Rolling Over from CL203 timepoints are 6, 12, 18, and 24 Months |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Canada |
France |
Israel |
Italy |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |