A Phase 2 Study to Evaluate the Dose and Pharmacodynamic Efficacy of Sialic Acid-Extended Release (SA-ER) Tablets in Patients With GNE Myopathy or Hereditary Inclusion Body Myopathy (GNE Myopathy)

June 14, 2016 updated by: Ultragenyx Pharmaceutical Inc

A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Dose and Pharmacodynamic Efficacy of Sialic Acid-Extended Release (SA-ER) Tablets in Patients With GNE Myopathy or Hereditary Inclusion Body Myopathy

GNE myopathy or hereditary inclusion body myopathy (HIBM) is a severe progressive metabolic myopathy caused by a defect in the biosynthetic pathway for sialic acid (SA).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

GNE myopathy or hereditary inclusion body myopathy (HIBM) is a severe progressive metabolic myopathy caused by a defect in the biosynthetic pathway for sialic acid (SA). Substrate replacement therapy is a potential therapeutic strategy based on the success of replacing missing SA and reducing muscle disease in a relevant mouse model of the human disease (Malicdan et al., 2009). Successful use of SA replacement therapy in humans is believed to depend upon providing steady long-term exposure to the compound in an extended release form (such as Sialic Acid-Extended Release [SA-ER]), given SA's short half-life. Following a Phase 1 study to establish the pharmacokinetics (PK) for SA-ER, Ultragenyx is conducting this study to assess the dose and potential pharmacodynamic effect of restoring sialylation of muscle by treatment with SA-ER at two dose levels as compared to placebo when administered over two 24 week periods of time. The study will also evaluate safety, as well as the effect of SA-ER on clinical measures of muscle strength, mobility, function and self-reported disability and quality of life. Effects on muscle volume/mass and function and on serum biomarkers will be evaluated as exploratory measures. These data should allow the selection of a dose and the appropriate design for a Phase 3 clinical study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
46

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Israel
      • Jerusalem, Israel, 91120
        • Hadassah University Hospital
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA Medical Center
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New York
      • New York, New York, United States, 10016
        • New York University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Must be between 18 and 65 years of age, inclusive.
  2. 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.
  3. Must have a documented diagnosis of GNE myopathy, 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 protocol.
  4. Must be able to walk 20 meters independently (may use orthotics and assistive devices).
  5. Must be able to provide reproducible force in bilateral elbow flexors and knee extensors during hand-held dynamometry testing (unilateral between test variability of < 15% for both muscle groups).
  6. Must be willing and able to comply with all study procedures including fine needle muscle biopsies of the upper (e.g., triceps brachii or posterior deltoid) and lower (e.g., biceps femoris or vastus lateralis) extremities at Baseline and 24 and 48 weeks.
  7. Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study.
  8. 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, or have had tubal ligation at least one year prior to Screening, or who have had total hysterectomy.

Exclusion Criteria:

  1. Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
  2. Use of any investigational product or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
  3. Ingestion of N-acetyl-D-mannosamine (ManNAc), SA, or related metabolites; intravenous immune globulin (IVIG); or anything that can be metabolized to produce SA in the body for the prior 60 days.
  4. 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.
  5. 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.
  6. Has a concurrent disease or condition that, in the view of the principal 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.
  7. Has serum transaminase (i.e., alanine aminotransferase [ALT], aspartate aminotransferase [AST], or gamma-glutamyl transpeptidase [GGT]) levels greater than three times the upper limit of normal or serum creatinine of greater than 2.0 mg/dL.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 6,000 mg SA-ER
Subjects will receive this dose for the duration of the study (total study duration of 48 weeks).
Drug: Sialic Acid Extended Release (SA-ER)
SA-ER will be administered in doses of 3000mg per day or 6000mg per day
Placebo Comparator: Placebo
Subjects will be randomized to the placebo arm for the first 24 weeks of the study. Then, subjects in this arm will be re-randomized into either the 3,000 mg per day or 6,000 mg per day arm for the remaining 24 weeks of the study (48 weeks total study duration).
Drug: Placebo
Subjects will be randomized to the placebo arm for the first 24 weeks of the study. Then, subjects in this arm will be re-randomized into either the 3,000 mg per day or 6,000 mg per day arm for the remaining 24 weeks of the study (total study duration 48 weeks).
Experimental: 3,000 mg SA-ER
Subjects will receive this dose for the duration of the study (total study duration of 48 weeks).
Drug: Sialic Acid Extended Release (SA-ER)
SA-ER will be administered in doses of 3000mg per day or 6000mg per day

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Evaluate the effect of SA-ER treatment on muscle sialylation, strength, and function in patients with HIBM.
Time Frame: Baseline, Week 24, and Week 48
To evaluate the effect of SA-ER treatment on improvement of biochemical measures of sialylation and pathology in muscle. On mobility, strength, and function using a series of quantitative and physical performance measures and quality of life using patient-reported outcome measures.
Baseline, Week 24, and Week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ultragenyx Pharmaceutical Inc

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Alan Pestronk, MD, Washington University School of Medicine
  • Principal Investigator: Perry Shieh, MD, University of California, Los Angeles
  • Principal Investigator: Yoseph Caraco, MD, Hadassah University Hospital
  • Principal Investigator: Heather Lau, MD, NYU Langone Health

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2012

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2013

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2013

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 17, 2012

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 20, 2012

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 25, 2012

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 16, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 14, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UX001-CL201

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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