Fabry DiseasePhase 2NCT00304512
A 12-Week Safety and Pharmacodynamic Study of AT1001 (Migalastat Hydrochloride) in Female Participants With Fabry Disease
A Phase 2 study testing migalastat HCl in people with Fabry Disease, run by Amicus Therapeutics at 6 sites in 6 countries.
Trial summary
Study to evaluate the safety, tolerability, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) in participants with Fabry disease. Read more about this study
- Who is it for?
- Ages 18 to 65 years, women only
- Conditions the study is for
- Fabry Disease
- What is being tested?
- migalastat HCl
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 6 sitesin 6 countries
- Study dates
- 7 Sep 2006to 9 May 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Females between 18 and 65 years of age (inclusive)
- Heterozygous for Fabry disease
- Had a confirmed diagnosis of Fabry disease with a documented missense gene mutation (individual or familial)
- Had enhanceable enzyme activity based on in vitro tests
- Were naïve to enzyme replacement therapy (ERT) and other therapies, except for palliative therapies for the signs and symptoms of Fabry disease, or stopped ERT for at least 18 weeks
- Had end organ dysfunction, even minimal, demonstrated by abnormal electrocardiogram (ECG) or evidence of left ventricular hypertrophy documented by echocardiogram or by cardiac biopsy; or renal insufficiency documented by common clinical assessments such as creatinine and glomerular filtration rate or by renal biopsy; or brain tissue dysfunction as documented by evidence of stroke (clinically or imaging); or peripheral nervous tissue dysfunction documented by complaints of intolerance to heat or cold, decreased vibratory sense and proprioception, decreased ability to perspire, or acroparesthesia.
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- Were willing to undergo 2 renal and 3 skin biopsies
- Agreed to be sexually abstinent or practice an effective method of contraception when engaging in sexual activity during the course of the study and for a period of 30 days following their completion of the study for women of childbearing potential.
- Were willing and able to provide written informed consent
Who cannot join
- Pregnant or lactating
- History of organ transplant
- History of significant disease other than Fabry disease (for example, end-stage renal disease; Class III or IV heart disease [per the New York Heart Association classification]; current diagnosis of cancer, except for basal cell carcinoma of the skin; diabetes [unless hemoglobin A1c ≤8]; or neurological disease that would have impaired the participant's ability to participate in the study)
- Serum creatinine >176 micromoles/liter on Day -2
- Screening 12-lead ECG demonstrating corrected QT interval >450 milliseconds
- Pacemaker or other contraindication for magnetic resonance imaging scanning
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- Taking a medication prohibited by the protocol: Fabrazyme® (agalsidase beta), Replagal™ (agalsidase alfa), Glyset® (miglitol), Zavesca® (miglustat), or any experimental therapy for any indication
- Participated in a previous clinical trial in the last 30 days
- Any other condition which, in the opinion of the investigator would jeopardize the safety of the participant or impact the validity of the study results.
Trial locations and contacts
6 sites in 6 countries.
6 sites in 6 countries
About this study
Official title: A Phase 2, Open-Label, Multiple Dose Level, 12-Week Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of AT1001 in Female Patients With Fabry Disease
Study to evaluate the safety, tolerability, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) in participants with Fabry disease.
Read the detailed description
This was a Phase 2, open-label study in female participants with Fabry disease. The study consisted of a 4-week screening period, during which participants' galactosidase (GLA) genotype was assessed for α-galactosidase A (α-Gal A) activity in response to migalastat. Participants were required to have α-Gal A activity responsive to migalastat. The study consisted of a 12-week treatment period, followed by an optional 36-week extension period. Participants received migalastat once every other day (QOD) for 12 weeks during the treatment period and the optional 36-week extension period for a total treatment duration of up to 48 weeks. Participants were stratified by α-Gal A enzyme activity (high >40%, and low ≤40%) then randomly assigned to receive migalastat at 1 of 3 specified dose levels (50, 150, or 250 milligrams [mg]).
- Conditions
- Fabry Disease
- Being tested
- migalastat HCl
- Keywords
- Amicus Therapeutics, AT1001, Galafold, Migalastat, Substrate
- Medical subject headings
- Fabry Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
migalastat HClDrug
Also called AT1001, Galafold, migalastat
| Study group | Role | What they receive |
|---|---|---|
| Migalastat Low Dose 50 mg | Experimental | Migalastat 50 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period. Receives: Drug: migalastat HCl |
| Migalastat Middle Dose 150 mg | Experimental | Migalastat 150 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period. Receives: Drug: migalastat HCl |
| Migalastat High Dose 250 mg | Experimental | Migalastat 250 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period. Receives: Drug: migalastat HCl |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
TEAEs were defined as any adverse event with start date on or after administration of study drug or pre-existing conditions that worsened on or after the start of the first study drug administration (on Day 1). A severe adverse event was defined as an adverse event that was incapacitating and required medical intervention. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through Week 48 is presented. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Measured: Day 1 (after dosing) through Week 48
Secondary outcomes (2)
PK: Area Under The Concentration Versus Time Curve (AUC) After Administration Of Migalastat
The AUC to the last measurable concentration (AUC0-t) was evaluated in plasma following a single oral dose of migalastat on Day 1 and following multiple oral doses on Day 14 (2 weeks) and Day 84 (12 weeks). All samples were collected on each dosing day.
Measured: 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 10 hours (postdose)
α-Gal A Activity In Leukocytes At Baseline, Week 12, And Week 48
Leukocytes were isolated from whole blood and lysed, and α-Gal A activity was measured using a validated fluorometric assay, with catalysis to fluorescent 4-methylumbelliferone (4-MU) as the activity measure. The activity values obtained were normalized to protein (measured using a colorimetric assay) and reported as enzyme activity (nanomole [nmol] 4-MU/hr) per mg of protein. On Day 1 of the first visit and at every visit thereafter, the samples were collected prior to dosing with migalastat. α-Gal A activity in leukocytes are presented by individual participants.
Measured: Baseline, Week 12 (end of treatment period), Week 48 (end of extension period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2006 (estimated)
- Study start7 Sep 2006
- Primary completion9 May 2008
- Study completion9 May 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Fabry DiseaseStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amicus Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Clinical Research, Study director, Amicus Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00304512
- Sponsor's protocol ID
- FAB-CL-204
- Status last verified
- Oct 2018
- First submitted
- 17 Mar 2006
- Last updated
- 3 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Benjamin ER, Della Valle MC, Wu X, Katz E, Pruthi F, Bond S, Bronfin B, Williams H, Yu J, Bichet DG, Germain DP, Giugliani R, Hughes D, Schiffmann R, Wilcox WR, Desnick RJ, Kirk J, Barth J, Barlow C, Valenzano KJ, Castelli J, Lockhart DJ. The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat. Genet Med. 2017 Apr;19(4):430-438. doi: 10.1038/gim.2016.122. Epub 2016 Sep 22.
PubMed 27657681Giugliani R, Waldek S, Germain DP, Nicholls K, Bichet DG, Simosky JK, Bragat AC, Castelli JP, Benjamin ER, Boudes PF. A Phase 2 study of migalastat hydrochloride in females with Fabry disease: selection of population, safety and pharmacodynamic effects. Mol Genet Metab. 2013 May;109(1):86-92. doi: 10.1016/j.ymgme.2013.01.009. Epub 2013 Jan 26.
PubMed 23474038
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Open-Label, Multiple Dose Level, 12-Week Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of AT1001 in Female Patients With Fabry Disease
- ClinicalTrials.gov ID
- NCT00304512
- Acronym / sponsor ID
- FAB-CL-204
- Conditions
- Fabry Disease
- Keywords
- Amicus Therapeutics, AT1001, Galafold, Migalastat, Substrate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Amicus TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 7 Sep 2006 (actual)
- Primary completion
- 9 May 2008 (actual)
- Study completion
- 9 May 2008 (actual)
- First posted
- 20 Mar 2006 (estimated)
- Results
- Posted 7 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study to evaluate the safety, tolerability, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) in participants with Fabry disease.
Detailed description
This was a Phase 2, open-label study in female participants with Fabry disease. The study consisted of a 4-week screening period, during which participants' galactosidase (GLA) genotype was assessed for α-galactosidase A (α-Gal A) activity in response to migalastat. Participants were required to have α-Gal A activity responsive to migalastat. The study consisted of a 12-week treatment period, followed by an optional 36-week extension period. Participants received migalastat once every other day (QOD) for 12 weeks during the treatment period and the optional 36-week extension period for a total treatment duration of up to 48 weeks. Participants were stratified by α-Gal A enzyme activity (high >40%, and low ≤40%) then randomly assigned to receive migalastat at 1 of 3 specified dose levels (50, 150, or 250 milligrams [mg]).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Migalastat Low Dose 50 mg | Experimental | Drug: migalastat HClMigalastat 50 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period. |
| Migalastat Middle Dose 150 mg | Experimental | Drug: migalastat HClMigalastat 150 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period. |
| Migalastat High Dose 250 mg | Experimental | Drug: migalastat HClMigalastat 250 mg was administered orally QOD during the 12-week treatment period and then during the optional 36-week treatment extension period. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Females between 18 and 65 years of age (inclusive)
- Heterozygous for Fabry disease
- Had a confirmed diagnosis of Fabry disease with a documented missense gene mutation (individual or familial)
- Had enhanceable enzyme activity based on in vitro tests
- Were naïve to enzyme replacement therapy (ERT) and other therapies, except for palliative therapies for the signs and symptoms of Fabry disease, or stopped ERT for at least 18 weeks
Key exclusion criteria (9 listed)
- Pregnant or lactating
- History of organ transplant
- History of significant disease other than Fabry disease (for example, end-stage renal disease; Class III or IV heart disease [per the New York Heart Association classification]; current diagnosis of cancer, except for basal cell carcinoma of the skin; diabetes [unless hemoglobin A1c ≤8]; or neurological disease that would have impaired the participant's ability to participate in the study)
- Serum creatinine >176 micromoles/liter on Day -2
- Screening 12-lead ECG demonstrating corrected QT interval >450 milliseconds
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 |
|---|---|---|
| migalastat HClAlso: AT1001, Galafold, migalastat | Drug | Migalastat High Dose 250 mg, Migalastat Low Dose 50 mg, Migalastat Middle Dose 150 mg |
Primary outcome
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
Time frame: Day 1 (after dosing) through Week 48
TEAEs were defined as any adverse event with start date on or after administration of study drug or pre-existing conditions that worsened on or after the start of the first study drug administration (on Day 1). A severe adverse event was defined as an adverse event that was incapacitating and required medical intervention. The number of participants who experienced one or more severe TEAEs after dosing on Day 1 through Week 48 is presented. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
2 secondary outcomes
PK: Area Under The Concentration Versus Time Curve (AUC) After Administration Of Migalastat
Time frame: 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 10 hours (postdose)
α-Gal A Activity In Leukocytes At Baseline, Week 12, And Week 48
Time frame: Baseline, Week 12 (end of treatment period), Week 48 (end of extension period)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27657681Benjamin ER, Della Valle MC, Wu X, Katz E, Pruthi F, Bond S, Bronfin B, Williams H, Yu J, Bichet DG, Germain DP, Giugliani R, Hughes D, Schiffmann R, Wilcox WR, Desnick RJ, Kirk J, Barth J, Barlow C, Valenzano KJ, Castelli J, Lockhart DJ. The validation of pharmacogenetics for the identification of Fabry patients to be treated with migalastat. Genet Med. 2017 Apr;19(4):430-438. doi: 10.1038/gim.2016.122. Epub 2016 Sep 22.
- Derived from this study: PubMed 23474038Giugliani R, Waldek S, Germain DP, Nicholls K, Bichet DG, Simosky JK, Bragat AC, Castelli JP, Benjamin ER, Boudes PF. A Phase 2 study of migalastat hydrochloride in females with Fabry disease: selection of population, safety and pharmacodynamic effects. Mol Genet Metab. 2013 May;109(1):86-92. doi: 10.1016/j.ymgme.2013.01.009. Epub 2013 Jan 26.
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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.
Medical Monitor, Clinical Research study director
Amicus Therapeutics
6 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing migalastat HCl in people with Fabry Disease, run by Amicus Therapeutics at 6 sites in 6 countries.
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 9 inclusion and 9 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 3 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States, Australia, Brazil, Canada, France and 1 more country. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) (time frame: Day 1 (after dosing) through Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00304512, which also lists 2 linked publications.
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 3 Oct 2018.