Fabry DiseasePhase 3AT1001-041NCT01458119
Open-Label Phase 3 Long-Term Safety Study of Migalastat
A Phase 3 study testing migalastat hydrochloride in people with Fabry Disease, run by Amicus Therapeutics at 25 sites in 13 countries.
Trial summary
This was a long-term, open-label study of migalastat (123 milligrams [mg] of migalastat [equivalent to 150 mg of migalastat hydrochloride]) (migalastat) in participants with Fabry disease who completed treatment in a previous monotherapy trial with migalastat. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Fabry Disease
- What is being tested?
- migalastat hydrochloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 85 participants
- Where
- 25 sitesin 13 countries
- Study dates
- 14 Oct 2011to 17 Feb 2016
- Phase
- Phase 3
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Completed migalastat treatment in a previous Fabry disease protocol
- Both male and female participants were enrolled
- Age 16 years or older
- Male and female participants had to agree to use protocol-identified acceptable contraception
Who cannot join
- Estimated glomerular filtration rate (eGFR) in the previous study was <30 milliliters/minute/1.73 square meters (mL/min/1.73 m^2) unless there was a measured GFR available within 3 m of the Baseline Visit that was >30 mL/min/1.73 m^2
- Had undergone, or was scheduled to undergo, kidney transplantation or was currently on dialysis
- Pregnant or breast feeding
- Treated with another investigational drug (except migalastat) within 30 days of study start
- Unable to comply with study requirements, or deemed otherwise unsuitable for study entry, in the opinion of the investigator
- Had documented transient ischemic attack, stroke, unstable angina, or myocardial infarction within the 12 m before the Baseline Visit
Show all 12Show fewer
- Had clinically significant, unstable cardiac disease in the opinion of the investigator
- Had a history of allergy or sensitivity to migalastat (including excipients) or to other iminosugars
- Required treatment with Glyset (miglitol) or Zavesca (miglustat)
- Had any intercurrent illness or condition that may have precluded the participant from fulfilling the protocol requirements
- Had a severe or unsuitable concomitant medical condition
- Had a clinically significant abnormal laboratory value and a clinically significant electrocardiogram finding at the Baseline Visit.
Trial locations and contacts
25 sites in 13 countries.
25 sites in 13 countries
United States11 sites
Study site
Atlanta, Georgia, 30322
Study site
Boston, Massachusetts, 02114
Study site
Chicago, Illinois, 60611
Study site
Dallas, Texas, 75246
Study site
Fairfax, Virginia, 22030
Study site
Grand Rapids, Michigan, 49525
Study site
Kansas City, Kansas, 66160
Study site
New York, New York, 10016
Study site
Pittsburgh, Pennsylvania, 15213
Study site
Portland, Oregon, 97239
Study site
Seattle, Washington, 98195
United Kingdom2 sites
Study site
London, NW3 2QG
Study site
Salford, M6 8HD
About this study
Official title: An Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Migalastat Hydrochloride Monotherapy in Subjects With Fabry Disease
This was a long-term, open-label study of migalastat (123 milligrams [mg] of migalastat [equivalent to 150 mg of migalastat hydrochloride]) (migalastat) in participants with Fabry disease who completed treatment in a previous monotherapy trial with migalastat.
Read the detailed description
Study AT1001-041 was an open-label, noncomparative, multicenter, long-term extension study for participants with Fabry disease who completed treatment in one of three previous trials of migalastat (AT1001-011 [NCT00925301], AT1001-012 [NCT01218659], or FAB-CL-205 [NCT00526071]). In these trials, migalastat was given as monotherapy. This was an extension study designed to evaluate the long-term safety and efficacy of migalastat for the treatment of Fabry disease. Study visits occurred every 6 months (m). Visit evaluations included physical examinations, clinical laboratory parameters, adverse events, and participant reported outcomes.
The study consisted of a Baseline Visit, which was performed at the time of the final visit of the previous study, followed by clinic visits every 6 m for each year of the study. Study assessments included a physical examination, echocardiography, laboratory parameters, and participant-reported outcomes. Since participants enrolled in the study at varying time points based on the completion of the preceding migalastat study, treatment duration varied among participants. No maximum treatment duration was defined. There were no control groups in this study; all participants received migalastat as a 150-mg capsule taken orally once every other day (QOD) and inactive reminder capsules on alternate days.
The sponsor (Amicus Therapeutics) discontinued Study AT1001-041 for logistical reasons and not due to either safety concerns or lack of efficacy. For participants who were ongoing in Study AT1001-041 at the time of discontinuation, the investigators were offered participation in a similar open-label, long-term migalastat treatment study (AT1001-042 [NCT02194985]) for participants ongoing at discontinuation.
- Conditions
- Fabry Disease
- Being tested
- migalastat hydrochloride
- Keywords
- Amicus Therapeutics, AT1001, Galafold, Migalastat
- 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 hydrochlorideDrug
Also called AT1001, Galafold, Migalastat
Oral capsule QOD
| Study group | Role | What they receive |
|---|---|---|
| Migalastat | Experimental | Migalastat 150-mg capsule taken orally QOD. The median duration of exposure was 23.5 m. Receives: Drug: migalastat hydrochloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered migalastat that did not necessarily have a causal relationship with the treatment. Each AE was recorded at the time of reporting; visits typically occurred every 6 months. A TEAE was defined as an AE starting on or after the first study drug administration date. Serious AEs were life-threatening or resulted in death, persistent or significant incapacitation, inpatient or prolonged hospitalization, or a congenital anomaly. The criteria for AE severity were: Mild: minimal discomfort, does not interfere with normal everyday activities; Moderate: sufficiently discomforting, interferes with normal everyday activities; Severe: prevents normal everyday activities. The number of participants experiencing TEAEs is presented for those who received migalastat treatment. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Measured: Baseline to End of Follow-up (30 days after the end of this 42-month study), with AE reporting occurring at each study visit, which occurred once every 6 months.
Secondary outcomes (1)
Annualized Rate Of Change In The Estimated Glomerular Filtration Rate (eGFR)
The annualized rate of change of the eGFR was assessed per participant by the slope of the simple linear regression between the observed values and the assessment times. It was calculated by using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (eGFR [CKD-EPI]) and the Modification of Diet in Renal Disease (MDRD) equation (eGFR [MDRD]). The equations are as follows:
eGFR [MDRD] = 175 * (Serum Creatinine)^-1.154 * (Age)^-0.203 * 1.212 (if black or African American) * 0.742 (if female); eGFR [CKD-EPI] = 141 * min(serum creatinine/kappa,1)^alpha * max(serum creatinine/kappa, 1)^-1.209 * 0.993^age * 1.1018(if female) * 1.159(if black or African American), where kappa is 0.7 for females and 0.9 for males, alpha is -0.329 for females and -0.411 for males, min is minimum of serum creatinine/kappa or 1, and max is the maximum of serum creatinine/kappa or 1. The number of participants with at least a Baseline and a post-Baseline value are presented.
Measured: Baseline, Every 6 m until the End of Study (42 m)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2011 (estimated)
- Study start14 Oct 2011
- Primary completion17 Feb 2016
- Study completion17 Feb 2016
Why it stopped: Amicus Therapeutics discontinued Study AT1001-041 for logistical reasons.
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 (1)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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 85 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
- NCT01458119
- Sponsor's protocol ID
- AT1001-041
- Other IDs
- 2011-004800-40
- Acronym
- AT1001-041
- Status last verified
- Oct 2018
- First submitted
- 20 Oct 2011
- Last updated
- 2 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Germain DP, Hughes DA, Nicholls K, Bichet DG, Giugliani R, Wilcox WR, Feliciani C, Shankar SP, Ezgu F, Amartino H, Bratkovic D, Feldt-Rasmussen U, Nedd K, Sharaf El Din U, Lourenco CM, Banikazemi M, Charrow J, Dasouki M, Finegold D, Giraldo P, Goker-Alpan O, Longo N, Scott CR, Torra R, Tuffaha A, Jovanovic A, Waldek S, Packman S, Ludington E, Viereck C, Kirk J, Yu J, Benjamin ER, Johnson F, Lockhart DJ, Skuban N, Castelli J, Barth J, Barlow C, Schiffmann R. Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat. N Engl J Med. 2016 Aug 11;375(6):545-55. doi: 10.1056/NEJMoa1510198.
PubMed 27509102
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Migalastat Hydrochloride Monotherapy in Subjects With Fabry Disease
- ClinicalTrials.gov ID
- NCT01458119
- Acronym / sponsor ID
- AT1001-041 / AT1001-041
- Conditions
- Fabry Disease
- Keywords
- Amicus Therapeutics, AT1001, Galafold, Migalastat
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Amicus Therapeutics discontinued Study AT1001-041 for logistical reasons.
- Enrolment
- 85 participants (actual)
- Lead sponsor
- Amicus TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 14 Oct 2011 (actual)
- Primary completion
- 17 Feb 2016 (actual)
- Study completion
- 17 Feb 2016 (actual)
- First posted
- 24 Oct 2011 (estimated)
- Results
- Posted 2 Oct 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This was a long-term, open-label study of migalastat (123 milligrams [mg] of migalastat [equivalent to 150 mg of migalastat hydrochloride]) (migalastat) in participants with Fabry disease who completed treatment in a previous monotherapy trial with migalastat.
Detailed description
Study AT1001-041 was an open-label, noncomparative, multicenter, long-term extension study for participants with Fabry disease who completed treatment in one of three previous trials of migalastat (AT1001-011 [NCT00925301], AT1001-012 [NCT01218659], or FAB-CL-205 [NCT00526071]). In these trials, migalastat was given as monotherapy. This was an extension study designed to evaluate the long-term safety and efficacy of migalastat for the treatment of Fabry disease. Study visits occurred every 6 months (m). Visit evaluations included physical examinations, clinical laboratory parameters, adverse events, and participant reported outcomes.
The study consisted of a Baseline Visit, which was performed at the time of the final visit of the previous study, followed by clinic visits every 6 m for each year of the study. Study assessments included a physical examination, echocardiography, laboratory parameters, and participant-reported outcomes. Since participants enrolled in the study at varying time points based on the completion of the preceding migalastat study, treatment duration varied among participants. No maximum treatment duration was defined. There were no control groups in this study; all participants received migalastat as a 150-mg capsule taken orally once every other day (QOD) and inactive reminder capsules on alternate days.
The sponsor (Amicus Therapeutics) discontinued Study AT1001-041 for logistical reasons and not due to either safety concerns or lack of efficacy. For participants who were ongoing in Study AT1001-041 at the time of discontinuation, the investigators were offered participation in a similar open-label, long-term migalastat treatment study (AT1001-042 [NCT02194985]) for participants ongoing at discontinuation.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Migalastat | Experimental | Drug: migalastat hydrochlorideMigalastat 150-mg capsule taken orally QOD. The median duration of exposure was 23.5 m. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Completed migalastat treatment in a previous Fabry disease protocol
- Both male and female participants were enrolled
- Age 16 years or older
- Male and female participants had to agree to use protocol-identified acceptable contraception
Key exclusion criteria (12 listed)
- Estimated glomerular filtration rate (eGFR) in the previous study was <30 milliliters/minute/1.73 square meters (mL/min/1.73 m^2) unless there was a measured GFR available within 3 m of the Baseline Visit that was >30 mL/min/1.73 m^2
- Had undergone, or was scheduled to undergo, kidney transplantation or was currently on dialysis
- Pregnant or breast feeding
- Treated with another investigational drug (except migalastat) within 30 days of study start
- Unable to comply with study requirements, or deemed otherwise unsuitable for study entry, in the opinion of the investigator
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 hydrochlorideAlso: AT1001, Galafold, MigalastatOral capsule QOD | Drug | Migalastat |
Primary outcome
Number Of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline to End of Follow-up (30 days after the end of this 42-month study), with AE reporting occurring at each study visit, which occurred once every 6 months.
An adverse event (AE) was defined as any untoward medical occurrence in a participant administered migalastat that did not necessarily have a causal relationship with the treatment. Each AE was recorded at the time of reporting; visits typically occurred every 6 months. A TEAE was defined as an AE starting on or after the first study drug administration date. Serious AEs were life-threatening or resulted in death, persistent or significant incapacitation, inpatient or prolonged hospitalization, or a congenital anomaly. The criteria for AE severity were: Mild: minimal discomfort, does not interfere with normal everyday activities; Moderate: sufficiently discomforting, interferes with normal everyday activities; Severe: prevents normal everyday activities. The number of participants experiencing TEAEs is presented for those who received migalastat treatment. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
1 secondary outcome
Annualized Rate Of Change In The Estimated Glomerular Filtration Rate (eGFR)
Time frame: Baseline, Every 6 m until the End of Study (42 m)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 27509102Germain DP, Hughes DA, Nicholls K, Bichet DG, Giugliani R, Wilcox WR, Feliciani C, Shankar SP, Ezgu F, Amartino H, Bratkovic D, Feldt-Rasmussen U, Nedd K, Sharaf El Din U, Lourenco CM, Banikazemi M, Charrow J, Dasouki M, Finegold D, Giraldo P, Goker-Alpan O, Longo N, Scott CR, Torra R, Tuffaha A, Jovanovic A, Waldek S, Packman S, Ludington E, Viereck C, Kirk J, Yu J, Benjamin ER, Johnson F, Lockhart DJ, Skuban N, Castelli J, Barth J, Barlow C, Schiffmann R. Treatment of Fabry's Disease with the Pharmacologic Chaperone Migalastat. N Engl J Med. 2016 Aug 11;375(6):545-55. doi: 10.1056/NEJMoa1510198.
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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
25 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing migalastat hydrochloride in people with Fabry Disease, run by Amicus Therapeutics at 25 sites in 13 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 4 inclusion and 12 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: stopped early, as of the sponsor's last update on 2 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 25 sites in United States, Australia, United Kingdom, Argentina, Belgium and 8 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 2 Oct 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 Experiencing Treatment-emergent Adverse Events (TEAEs) (time frame: Baseline to End of Follow-up (30 days after the end of this 42-month study), with AE reporting occurring at each study visit, which occurred once every 6 months.). 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 NCT01458119, which also lists 1 linked publication.
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 2 Oct 2018.