search
Back to results

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

Primary Purpose

GNE Myopathy, Hereditary Inclusion Body Myopathy (HIBM)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
SA-ER 500 mg
SA-IR 500 mg
Sponsored by
Ultragenyx Pharmaceutical Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for GNE Myopathy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UCLA Medical Center
  • Washington University School of Medicine
  • NYU Medical Center
  • Hadassah University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Crossover Participants

Naïve Participants

Arm Description

Participants completing the 48-week study (UX001-CL201; NCT01517880) were enrolled into Part I of the study: Part I: participants continued on 6 g/day SA-ER for 12 weeks Part II: 12 g/day SA (1.5 g of SA-ER and 1.5 g of SA-IR treatment 4 times per day [QID]) for 36 months Part III: 6 g/day or 12 g/day SA (both SA-ER and SA-IR) Part IV: 6 g/day or 12 g/day SA (SA-ER only)

Treatment naïve participants with GNE myopathy were enrolled into Part II of the study: Part II: 12 g/day SA (1.5 g of SA-ER and 1.5 g of SA-IR treatment QID) for 36 months Part III: 6 g/day or 12 g/day SA (both SA-ER and SA-IR) Part IV: 6 g/day or 12 g/day SA (SA-ER only)

Outcomes

Primary Outcome Measures

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.
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.
Interval History: Has the Participant Started Taking Any New Medications or Discontinued Any Medications Since the 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.
Interval History: Has the Participant Started Receiving Any New Therapy or Discontinued Any Therapies 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.
Interval History: Typical Number of Falls Per Year
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.

Secondary Outcome Measures

Full Information

First Posted
April 10, 2013
Last Updated
March 16, 2018
Sponsor
Ultragenyx Pharmaceutical Inc
search

1. Study Identification

Unique Protocol Identification Number
NCT01830972
Brief Title
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
Official Title
An Open-label Phase 2 Extension Study to Evaluate the Long Term Safety and Efficacy of Sialic Acid-Extended Release (SA-ER) Tablets and Sialic Acid-Immediate Release (SA-IR) Capsules in Patients With GNE Myopathy or Hereditary Inclusion Body Myopathy
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
June 4, 2013 (Actual)
Primary Completion Date
February 14, 2017 (Actual)
Study Completion Date
February 14, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ultragenyx Pharmaceutical Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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]).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
GNE Myopathy, Hereditary Inclusion Body Myopathy (HIBM)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
59 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Crossover Participants
Arm Type
Experimental
Arm Description
Participants completing the 48-week study (UX001-CL201; NCT01517880) were enrolled into Part I of the study: Part I: participants continued on 6 g/day SA-ER for 12 weeks Part II: 12 g/day SA (1.5 g of SA-ER and 1.5 g of SA-IR treatment 4 times per day [QID]) for 36 months Part III: 6 g/day or 12 g/day SA (both SA-ER and SA-IR) Part IV: 6 g/day or 12 g/day SA (SA-ER only)
Arm Title
Naïve Participants
Arm Type
Experimental
Arm Description
Treatment naïve participants with GNE myopathy were enrolled into Part II of the study: Part II: 12 g/day SA (1.5 g of SA-ER and 1.5 g of SA-IR treatment QID) for 36 months Part III: 6 g/day or 12 g/day SA (both SA-ER and SA-IR) Part IV: 6 g/day or 12 g/day SA (SA-ER only)
Intervention Type
Drug
Intervention Name(s)
SA-ER 500 mg
Intervention Description
oral tablets
Intervention Type
Drug
Intervention Name(s)
SA-IR 500 mg
Intervention Description
oral capsules
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation
Description
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
Title
Clinically Significant Changes From Baseline in Vital Signs, Physical and Neurological Examination Findings and Laboratory Evaluations
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
Title
Interval History: Has the Participant Experienced Any New Conditions or Exacerbations of an Existing Condition Since Last Study Visit?
Description
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
Title
Interval History: Has the Participant Started Taking Any New Medications or Discontinued Any Medications Since the Study Visit?
Description
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
Title
Interval History: Has the Participant Started Receiving Any New Therapy or Discontinued Any Therapies Since Last Study Visit?
Description
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
Title
Interval History: Typical Number of Falls Per Year
Description
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, 6, 12, 18, 24, 30, 36, study termination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
NYU Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Hadassah University Hospital
City
Jerusalem
Country
Israel

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs