An Open Label Phase 2 Extension Study of Higher Dose Sialic Acid-Extended Release (SA-ER) Tablets and Sialic Acid-Immediate Release (SA-IR) Capsules in Patients With Glucosamine (UDP-N-acetyl)-2-Epimerase (GNE) Myopathy

Ultragenyx Pharmaceutical Inc59 enrolled

Overview

The safety objectives of the study are to: evaluate additional long-term safety of SA-ER treatment of participants with GNE myopathy previously treated with SA-ER at dose of 6g/day (Part I); evaluate the safety of 12g /day SA (delivered by 1.5g of SA-ER tablets and 1.5g of SA-IR capsules 4 times per day) in the treatment of participants with GNE myopathy (Part II) over a 6 month treatment period; evaluate the safety of SA treatment at both 6g/day and 12 g/day (Part III \[SA-ER/SA-IR\] and Part IV \[SA-ER\]).

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

GNE Myopathy Hereditary Inclusion Body Myopathy (HIBM)

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Enrollment in, and successful completion of the UX001-CL201 (NCT01517880) protocol OR (for 10 treatment naïve subjects): * Have a confirmed diagnosis of GNE Myopathy * Aged 18 -65 years of age, inclusive * Able to walk ≥ 200 meters and \< 80% of predicted normal during the 6-Minute Walk Test (6MWT; orthotics and assistive devices allowed) * Must be willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures * Must be willing and able to comply with all study procedures * Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study * Females of childbearing potential must have a negative pregnancy test at Baseline 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, or have had tubal ligation at least one year prior to Baseline, or who have had total hysterectomy Exclusion Criteria: * Use of any investigational product (other than SA-ER tablets) to treat GNE myopathy * Ingestion of N-acetyl-D-mannosamine (ManNAc) or similar SA-producing compounds * Pregnant or breastfeeding at Baseline or planning to become pregnant (self or partner) at any time during the study * 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 * Have any co-morbid conditions, including unstable major organ-system disease(s) that in the opinion of the investigator, places the subject at increased risk of complications, interferes with study participation or compliance, or confounds study objectives.

Locations (4)

UCLA Medical Center

Los Angeles, California, United States

Washington University School of Medicine

St Louis, Missouri, United States

NYU Medical Center

New York, New York, United States

Hadassah University Hospital

Jerusalem, Israel

Outcomes

Primary Outcomes

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation

An adverse event (AE) is defined as any untoward medical occurrence, whether or not considered drug related. A serious AE (SAE) is an AE that at any dose results in any of the following: death, a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect. TEAEs include all adverse events that start on or after the first dose of study medication, or adverse events that are present prior to the first dose of study medication, but their severity or relationship increases after the first dose of study medication up to and including 30 days after the final study medication dosing date. TEAEs were graded as mild (grade 1), moderate (grade 2), severe (grade 3), life-threatening (grade 4), or death (grade 5). TEAE relationship to study medication was classified as not related, possibly related, or probably related.

Time frame: From first dose of study drug until up to 30 days after the last dose of study drug. Mean (SD) duration of treatment was 1170.0 (170.2) days for Crossover Participants and 897 (380) days for Naïve Participants

Clinically Significant Changes From Baseline in Vital Signs, Physical and Neurological Examination Findings and Laboratory Evaluations

Interval History: Has the Participant Experienced Any New Conditions or Exacerbations of an Existing Condition Since Last Study Visit?

Each interval history was intended to record any signs, symptoms, or events (e.g., falls, changes in medications or therapies) experienced by the participant since the prior study visit that were not related to study procedure(s) performed at prior study visits or study drug. Interval history may have included exacerbation or improvement in existing medical conditions (including the clinical manifestations of GNE myopathy) that might have interfered with study participation, safety, and/or positively or negatively impact performance of functional assessments.

Time frame: Part I: Baseline (Study UX001-CL201 Week 48), Month 6; Part II-IV: Baseline, Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 33, 36, study termination

Interval History: Has the Participant Started Taking Any New Medications or Discontinued Any Medications Since the Study Visit?

Time frame: Part I: Baseline (Study UX001-CL201 Week 48), Month 6; Part II-IV: Baseline, Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 33, 36, study termination

Interval History: Has the Participant Started Receiving Any New Therapy or Discontinued Any Therapies Since Last Study Visit?

Time frame: Part I: Baseline (Study UX001-CL201 Week 48), Month 6; Part II-IV: Baseline, Months 1, 3, 6, 9, 12, 15, 18, 21, 24, 27, 33, 36, study termination

Interval History: Typical Number of Falls Per Year

Time frame: Part I: Baseline (Study UX001-CL201 Week 48), Month 6; Part II-IV: Baseline, Months 1, 6, 12, 18, 24, 30, 36, study termination