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

NCT01517880 | Completed Phase 2 DMC

• 1 other identifier: UX001-CL201
• Study Type: interventional
• Target: 46
• Locations: 2 countries
• Sites: 4

Brief Summary

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).

Conditions

GNE Myopathy; Hereditary Inclusion Body Myopathy

Keywords

Hereditary Inclusion Body Myopathy (HIBM); GNE myopathies; distal myopathy with rimmed vacuoles [DMRV]; Nonaka disease

Outcome Measures

Primary Outcomes (1)

• Evaluate the effect of SA-ER treatment on muscle sialylation, strength, and function in patients with HIBM.

  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

Study Arms (3)

6,000 mg SA-ER

EXPERIMENTAL

Subjects will receive this dose for the duration of the study (total study duration of 48 weeks).

Drug: Sialic Acid Extended Release (SA-ER)

Placebo

PLACEBO COMPARATOR

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

3,000 mg SA-ER

EXPERIMENTAL

Subjects will receive this dose for the duration of the study (total study duration of 48 weeks).

Drug: Sialic Acid Extended Release (SA-ER)

Interventions

Sialic Acid Extended Release (SA-ER) DRUG

SA-ER will be administered in doses of 3000mg per day or 6000mg per day

3,000 mg SA-ER; 6,000 mg SA-ER

Placebo DRUG

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).

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be between 18 and 65 years of age, inclusive.
• 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 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.
• Must be able to walk 20 meters independently (may use orthotics and assistive devices).
• 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).
• 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.
• 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 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.

You may not qualify if:

• Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• Ultragenyx Pharmaceutical Inc: lead

Study Sites (4)

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

New York University School of Medicine

New York, New York, 10016, United States

Location

Hadassah University Hospital

Jerusalem, 91120, Israel

Location

MeSH Terms

Conditions

Distal myopathy, Nonaka type

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2012
• First Posted: January 25, 2012
• Study Start: May 1, 2012
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: June 16, 2016

Record last verified: 2016-06

Locations

US (3); IL (1)