Hereditary Inclusion Body Myopathy (HIBM)Phase 1NCT01359319
Safety and Pharmacokinetics of Sialic Acid Tables in Patients With Hereditary Inclusion Body Myopathy (HIBM)
A Phase 1 study testing Sialic Acid Extended Release (SA-ER) Tablets and Sialic Acid Extended Release (SA-ER) Tables in people with Hereditary Inclusion Body Myopathy (HIBM), run by Ultragenyx Pharmaceutical Inc at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hereditary Inclusion Body Myopathy (HIBM)
- What is being tested?
- Sialic Acid Extended Release (SA-ER) Tablets and Sialic Acid Extended Release (SA-ER) Tables
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2011to May 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must be 18 years to 70 years of age.
- 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, 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.
- Willing and able to comply with all study procedures, including multiple overnight stays at a hospital unit or Phase 1 unit.
- 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.
- 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.
Who cannot join
- 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 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.
- Presence of a condition the severity and acuity of which, in the opinion of the investigator, warrant immediate surgical intervention or other treatment.
- 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.
- Presence of a concurrent disease or condition that would interfere with study participation or affect safety such as swallowing difficulties.
- 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.
- Serum transaminase (ALT, AST, GGT) levels > 3 x upper limit of normal (ULN) or serum creatinine > 2.0 mg/dL.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
West Coast Clinical Trials
Costa Mesa, California, 92626
Clinilabs
New York, New York, 10019
About this study
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)
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.
- Being tested
- Sialic Acid Extended Release (SA-ER) Tablets, Sialic Acid Extended Release (SA-ER) Tables
- Keywords
- Phase 1 Safety and Pharmacokinetic Study
- Medical subject headings
- Distal myopathy, Nonaka type
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sialic Acid Extended Release (SA-ER) TabletsDrug
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) TablesDrug
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) TabletsDrug
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) TabletsDrug
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) TabletsDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 650 mg (single dose only) | Experimental | Each patient will be sequentially assigned to a specific dose level and will receive two single-dose exposures at that same dose level (fasted and fed). The low-dose cohorts will be filled before assigning higher-dose cohorts. The patient will then be assigned to receive one repeat-dose regimen. The lower-dose repeat-dose cohorts will be filled before proceeding to higher repeat-dose levels. Receives: Drug: Sialic Acid Extended Release (SA-ER) Tablets |
| 1,950 mg (single and repeat dose) | Experimental | Each patient will be sequentially assigned to a specific dose level and will receive two single-dose exposures at that same dose level (fasted and fed). The low-dose cohorts will be filled before assigning higher-dose cohorts. The patient will then be assigned to receive one repeat-dose regimen. The lower-dose repeat-dose cohorts will be filled before proceeding to higher repeat-dose levels. Receives: Drug: Sialic Acid Extended Release (SA-ER) Tables |
| 2,925 mg (single and repeat dose) | Experimental | Each patient will be sequentially assigned to a specific dose level and will receive two single-dose exposures at that same dose level (fasted and fed). The low-dose cohorts will be filled before assigning higher-dose cohorts. The patient will then be assigned to receive one repeat-dose regimen. The lower-dose repeat-dose cohorts will be filled before proceeding to higher repeat-dose levels. Receives: Drug: Sialic Acid Extended Release (SA-ER) Tablets |
| 4,875 mg (single and repeat dose) | Experimental | Each patient will be sequentially assigned to a specific dose level and will receive two single-dose exposures at that same dose level (fasted and fed). The low-dose cohorts will be filled before assigning higher-dose cohorts. The patient will then be assigned to receive one repeat-dose regimen. The lower-dose repeat-dose cohorts will be filled before proceeding to higher repeat-dose levels. Receives: Drug: Sialic Acid Extended Release (SA-ER) Tablets |
| 6,000 mg (single and repeat dose) | Experimental | Each patient will be sequentially assigned to a specific dose level and will receive two single-dose exposures at that same dose level (fasted and fed). The low-dose cohorts will be filled before assigning higher-dose cohorts. The patient will then be assigned to receive one repeat-dose regimen. The lower-dose repeat-dose cohorts will be filled before proceeding to higher repeat-dose levels. Receives: Drug: Sialic Acid Extended Release (SA-ER) Tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Secondary outcomes (1)
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.
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2011 (estimated)
- Study startJul 2011
- Primary completionApr 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hereditary Inclusion Body Myopathy (HIBM)Studies of the same condition, open and under way.
- More trials run by Ultragenyx Pharmaceutical IncThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ultragenyx Pharmaceutical Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01359319
- Sponsor's protocol ID
- UX001-CL101
- Status last verified
- Feb 2012
- First submitted
- 20 May 2011
- Last updated
- 21 May 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01359319
- Acronym / sponsor ID
- UX001-CL101
- Keywords
- Phase 1 Safety and Pharmacokinetic Study
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Ultragenyx Pharmaceutical IncIndustry (pharma, biotech, devices)
- Study start
- Jul 2011
- Primary completion
- Apr 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 24 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 650 mg (single dose only) | Experimental | Drug: Sialic Acid Extended Release (SA-ER) TabletsEach patient will be sequentially assigned to a specific dose level and will receive two single-dose exposures at that same dose level (fasted and fed). The low-dose cohorts will be filled before assigning higher-dose cohorts. The patient will then be assigned to receive one repeat-dose regimen. The lower-dose repeat-dose cohorts will be filled before proceeding to higher repeat-dose levels. |
| 1,950 mg (single and repeat dose) | Experimental | Drug: Sialic Acid Extended Release (SA-ER) TablesEach patient will be sequentially assigned to a specific dose level and will receive two single-dose exposures at that same dose level (fasted and fed). The low-dose cohorts will be filled before assigning higher-dose cohorts. The patient will then be assigned to receive one repeat-dose regimen. The lower-dose repeat-dose cohorts will be filled before proceeding to higher repeat-dose levels. |
| 2,925 mg (single and repeat dose) | Experimental | Drug: Sialic Acid Extended Release (SA-ER) TabletsEach patient will be sequentially assigned to a specific dose level and will receive two single-dose exposures at that same dose level (fasted and fed). The low-dose cohorts will be filled before assigning higher-dose cohorts. The patient will then be assigned to receive one repeat-dose regimen. The lower-dose repeat-dose cohorts will be filled before proceeding to higher repeat-dose levels. |
| 4,875 mg (single and repeat dose) | Experimental | Drug: Sialic Acid Extended Release (SA-ER) TabletsEach patient will be sequentially assigned to a specific dose level and will receive two single-dose exposures at that same dose level (fasted and fed). The low-dose cohorts will be filled before assigning higher-dose cohorts. The patient will then be assigned to receive one repeat-dose regimen. The lower-dose repeat-dose cohorts will be filled before proceeding to higher repeat-dose levels. |
| 6,000 mg (single and repeat dose) | Experimental | Drug: Sialic Acid Extended Release (SA-ER) TabletsEach patient will be sequentially assigned to a specific dose level and will receive two single-dose exposures at that same dose level (fasted and fed). The low-dose cohorts will be filled before assigning higher-dose cohorts. The patient will then be assigned to receive one repeat-dose regimen. The lower-dose repeat-dose cohorts will be filled before proceeding to higher repeat-dose levels. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Must be 18 years to 70 years of age.
- 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, 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.
- Willing and able to comply with all study procedures, including multiple overnight stays at a hospital unit or Phase 1 unit.
- 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.
Key exclusion criteria (8 listed)
- 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 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.
- Presence of a condition the severity and acuity of which, in the opinion of the investigator, warrant immediate surgical intervention or other treatment.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sialic Acid Extended Release (SA-ER) TabletsPatients 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. | Drug | 650 mg (single dose only) |
| Sialic Acid Extended Release (SA-ER) TablesPPatients 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. | Drug | 1,950 mg (single and repeat dose) |
| Sialic Acid Extended Release (SA-ER) TabletsPatients 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. | Drug | 2,925 mg (single and repeat dose) |
| Sialic Acid Extended Release (SA-ER) TabletsPatients 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. | Drug | 4,875 mg (single and repeat dose) |
| Sialic Acid Extended Release (SA-ER) TabletsPatients 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. | Drug | 6,000 mg (single and repeat dose) |
Primary outcome
Evaluate the safety of repeated doses of Sialic Acid - Extended Release (SA-ER) tablets in patients with HIBM
Time frame: 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.
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.
1 secondary outcome
Evaluate the pharmacokinetics of SA-ER after single and repeated dosing.
Time frame: 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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sialic Acid Extended Release (SA-ER) Tablets and Sialic Acid Extended Release (SA-ER) Tables in people with Hereditary Inclusion Body Myopathy (HIBM), run by Ultragenyx Pharmaceutical Inc at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the safety of repeated doses of Sialic Acid - Extended Release (SA-ER) tablets in patients with HIBM (time frame: 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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2012.