Safety and Pharmacokinetics of Sialic Acid Tables in Patients With Hereditary Inclusion Body Myopathy (HIBM)

Hereditary Inclusion Body Myopathy (HIBM) Clinical Trial

Official title:

A Phase 1 Study to Evaluate the Safety and Pharmacokinetics of Single and Repeat Doses of Sialic Acid Extended Release (SA-ER) Tables in Patients With Hereditary Inclusion Body Myopathy (HIBM)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01359319
• Other study ID #: UX001-CL101
• Status: Completed
• Phase: Phase 1
• First received: May 20, 2011
• Last updated: May 17, 2012
• Start date: July 2011
• Est. completion date: May 2012

Study information

• Verified date: February 2012
• Source: Ultragenyx Pharmaceutical Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

Hereditary Inclusion Body Myopathy (HIBM) is a severe progressive metabolic myopathy caused by a defect in the biosynthetic pathway for sialic acid (SA), a critical component of many muscle proteins, resulting in a deficiency in SA in the muscles of HIBM patients.

The effective replacement of the missing SA substrate is theoretically simple, and, in animal models, replacement with SA showed significant restoration of sialylation biochemistry and excellent reduction in muscle disease. These data show that replacement can achieve significant clinical benefit in muscle pathology, function, and survival.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: May 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Must be 18 years to 70 years of age.

2. 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, confirmed by genetic testing, of hereditary inclusion body myopathy (HIBM), also known as distal myopathy, rimmed vacuoles (DMRV), or Nonaka myopathy due to demonstrated mutations in gene encoding the GNE/MNK enzyme.

4. Willing and able to comply with all study procedures, including multiple overnight stays at a hospital unit or Phase 1 unit.

5. Sexually active subjects must be willing to use an acceptable method of contraception (i.e double barrier method)while participating in the study and for 30 days after receiving the last dose of SA-ER.

6. 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 at least 2 years, or had bilateral tubal ligation at least 1 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 ManNAc, sialic acid, or related metabolites or sialic acid donors that provide this substrate in either chemical or nutritional supplement form during the 30 days prior to screening. If ManNAc or other substrate was used more than 30 days prior to screening, the time period of use, the compound used, and the dose and dose regimen should be recorded in the patient's history. If a patient has been on substrate replacement therapy in the past, the investigator must consider the potential confounding effects of this therapy before enrolling the patient.

4. Presence of a condition the severity and acuity of which, in the opinion of the investigator, warrant immediate surgical intervention or other treatment.

5. Presence or history of any hypersensitivity to SA or its excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects.

6. Presence of a concurrent disease or condition that would interfere with study participation or affect safety such as swallowing difficulties.

7. Presence or history of any condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study.

8. Serum transaminase (ALT, AST, GGT) levels > 3 x upper limit of normal (ULN) or serum creatinine > 2.0 mg/dL.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hereditary Inclusion Body Myopathy (HIBM)
• Muscular Diseases

Intervention

Drug:
• Sialic Acid Extended Release (SA-ER) Tablets
Patients will receive SA-ER tablets orally at one of five (5) dose levels in the single-dose phase,phase and one of four (4) dose levels in the repeat-dose phase. During repeat dosing, the total daily dose will be divided evenly into three doses given in the morning, in the evening, and at bedtime (qHS). No placebo or active comparator will be administered and the study drug will be administered on an open-label basis.
• Sialic Acid Extended Release (SA-ER) Tables
PPatients will receive SA-ER tablets orally at one of five (5) dose levels in the single-dose phase,phase and one of four (4) dose levels in the repeat-dose phase. During repeat dosing, the total daily dose will be divided evenly into three doses given in the morning, in the evening, and at bedtime (qHS). No placebo or active comparator will be administered and the study drug will be administered on an open-label basis.
• Sialic Acid Extended Release (SA-ER) Tablets
Patients will receive SA-ER tablets orally at one of five (5) dose levels in the single-dose phase,phase and one of four (4) dose levels in the repeat-dose phase. During repeat dosing, the total daily dose will be divided evenly into three doses given in the morning, in the evening, and at bedtime (qHS). No placebo or active comparator will be administered and the study drug will be administered on an open-label basis.
• Sialic Acid Extended Release (SA-ER) Tablets
Patients will receive SA-ER tablets orally at one of five (5) dose levels in the single-dose phase,phase and one of four (4) dose levels in the repeat-dose phase. During repeat dosing, the total daily dose will be divided evenly into three doses given in the morning, in the evening, and at bedtime (qHS). No placebo or active comparator will be administered and the study drug will be administered on an open-label basis.
• Sialic Acid Extended Release (SA-ER) Tablets
Patients will receive SA-ER tablets orally at one of five (5) dose levels in the single-dose phase,phase and one of four (4) dose levels in the repeat-dose phase. During repeat dosing, the total daily dose will be divided evenly into three doses given in the morning, in the evening, and at bedtime (qHS). No placebo or active comparator will be administered and the study drug will be administered on an open-label basis.

Locations

Country	Name	City	State
United States	West Coast Clinical Trials	Costa Mesa	California
United States	Clinilabs	New York City	New York

Sponsors (1)

Lead Sponsor	Collaborator
Ultragenyx Pharmaceutical Inc

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the safety of repeated doses of Sialic Acid - Extended Release (SA-ER) tablets in patients with HIBM	Safety will be evaluated in terms of the incidence and frequency of treatment-emergent adverse events (TEAEs), including clinically significant changes from baseline to scheduled timepoints in clinical laboratory values, vital signs, or physical and neurologic examination findings. Medical history and reported clinical symptoms, including increasing muscle weakness, fatigue, or pain.	Each patient may participate approximately 4-6 weeks total, including 2 single dose (fast/fed) treatment periods followed by a 7-day repeat treatment period.	Yes
Secondary	Evaluate the pharmacokinetics of SA-ER after single and repeated dosing.	Evaluation of the pharmacokinetics of SA-ER will include Cmax, the AUC of single doses, and steady-state levels of free, soluble sialic acid in serum after repeated dosing.	Multiple pharmacokinetic (serum) samples will be taken during the study, at baseline, after each single dose administration, and at the final day of the 7 day repeat dose period.	No