Fabry DiseasePhase 2NCT00214500
A Study of AT1001 (Migalastat Hydrochloride) in Participants With Fabry Disease
A Phase 2 study testing migalastat HCl in people with Fabry Disease, run by Amicus Therapeutics at 5 sites in United States.
Trial summary
Study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) in participants with Fabry disease. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men 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
- 5 sitesUnited States
- Study dates
- 2 Jan 2006to 29 Jan 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 55 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- Males between 18 and 55 years of age (inclusive)
- Hemizygous for Fabry disease
- Had a confirmed diagnosis of Fabry disease with a documented missense gene mutation (individual or familial)
- Had enhanceable enzyme activity
- In the judgment of the investigator, were either able to safely suspend ERT throughout the study, or be ERT naive
- Agreed to be sexually abstinent or use a condom with spermicide when engaging in sexual activity during the course of the study and for a period of 30 days following completion of the study
- Were willing and able to sign an informed consent form
Who cannot join
- 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)
- History of organ transplant
- Serum creatinine >2 mg per deciliter on Day -2
- Screening 12-lead electrocardiogram demonstrating corrected QT interval >450 milliseconds prior to dosing
- 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
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Study site
Bethesda, Maryland, 20892
Study site
Decatur, Georgia, 30033
Study site
Houston, Texas, 77030
Study site
Los Angeles, California, 90048
Study site
New York, New York, 10016
About this study
Official title: A Phase 2, Open-Label, Multicenter, 12-Week Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AT1001 in Patients With Fabry Disease
Study to evaluate the safety, tolerability, pharmacokinetics, 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 male participants with Fabry disease. All participants who met initial eligibility criteria underwent a 28-day screening period, including a 14-day run-in with migalastat (150 milligrams [mg] migalastat once a day [QD] from Days -28 to -15) to assess eligibility for entering the treatment period of the study. Participants who entered the treatment period were required to have α-galactosidase A (α-Gal A) activity responsive to migalastat.
Fifteen participants received at least 1 dose of study drug, however, 6 of these participants did not demonstrate α-Gal A activity responsive to migalastat and were thus screen failures (these participants are hereafter referred to as "dosed screen failures") due to not meeting all inclusion criteria for treatment. Therefore, 9 participants were enrolled into the treatment period (these participants are hereafter referred to as "eligible-enrolled").
Eligible-enrolled participants (those who satisfied the criteria for inclusion in the study) received escalating doses of migalastat twice a day (BID) for 6 weeks (Days 1 to 42), followed by 6 weeks at 1 dose level BID (Days 43 to 84) during the treatment period. Participants could then opt to participate in the extension period. The study consisted of 2 optional extension periods, the first through Week 48 and the second through Week 96. For participants who did not continue into the optional treatment extension, the study included a 2-week follow-up period.
- 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 | Experimental | Migalastat was administered orally during the 12-week treatment period and then during the optional 2 treatment extension periods.
Treatment Period:
* Migalastat 25 mg BID for Weeks 1 and 2 (Day 1 through the morning dose on Day 14).
* Migalastat 100 mg BID for Weeks 3 and 4 (Day 15 through the morning dose on Day 28).
* Migalastat 250 mg BID for Weeks 5 and 6 (Day 29 through the morning dose on Day 42).
* Migalastat 25 mg BID for Weeks 6 to 12 (Days 43 to 84).
Extension Period:
* Migalastat 25 mg BID for Weeks 12 through 48.
* Migalastat 50 mg QD for Weeks 48 through 96. 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 96 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 96
Secondary outcomes (2)
PK: Area Under The Concentration Versus Time Curve (AUC) After Administration Of Migalastat
The AUC from time zero to 12 hours (hr) postdose (AUC0-12) was evaluated in plasma following a single dose of migalastat 25, 100, and 250 mg on Days 1, 15, and 29, respectively. In addition, AUC0-12 was assessed following multiple doses (14 days) of migalastat 25, 100, and 250 mg on Days 14, 28, and 42, respectively.
Measured: 0 (predose), 0.5, 1, 2, 3, 4, 5, 6, 8, and 10 hr (postdose)
α-Galactosidase A (α-Gal A) Activity In Leukocytes At Baseline, Week 12, And Week 96
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 96 (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 posted22 Sep 2005 (estimated)
- Study start2 Jan 2006
- Primary completion29 Jan 2008
- Study completion29 Jan 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 (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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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
- NCT00214500
- Sponsor's protocol ID
- FAB-CL-201 (AA1565520)
- Status last verified
- Oct 2018
- First submitted
- 13 Sep 2005
- Last updated
- 30 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 27657681
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Open-Label, Multicenter, 12-Week Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AT1001 in Patients With Fabry Disease
- ClinicalTrials.gov ID
- NCT00214500
- Acronym / sponsor ID
- FAB-CL-201 (AA1565520)
- 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
- 2 Jan 2006 (actual)
- Primary completion
- 29 Jan 2008 (actual)
- Study completion
- 29 Jan 2008 (actual)
- First posted
- 22 Sep 2005 (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, pharmacokinetics, and pharmacodynamics of migalastat hydrochloride (HCl) (migalastat) in participants with Fabry disease.
Detailed description
This was a Phase 2, open-label study in male participants with Fabry disease. All participants who met initial eligibility criteria underwent a 28-day screening period, including a 14-day run-in with migalastat (150 milligrams [mg] migalastat once a day [QD] from Days -28 to -15) to assess eligibility for entering the treatment period of the study. Participants who entered the treatment period were required to have α-galactosidase A (α-Gal A) activity responsive to migalastat.
Fifteen participants received at least 1 dose of study drug, however, 6 of these participants did not demonstrate α-Gal A activity responsive to migalastat and were thus screen failures (these participants are hereafter referred to as "dosed screen failures") due to not meeting all inclusion criteria for treatment. Therefore, 9 participants were enrolled into the treatment period (these participants are hereafter referred to as "eligible-enrolled").
Eligible-enrolled participants (those who satisfied the criteria for inclusion in the study) received escalating doses of migalastat twice a day (BID) for 6 weeks (Days 1 to 42), followed by 6 weeks at 1 dose level BID (Days 43 to 84) during the treatment period. Participants could then opt to participate in the extension period. The study consisted of 2 optional extension periods, the first through Week 48 and the second through Week 96. For participants who did not continue into the optional treatment extension, the study included a 2-week follow-up period.
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 HClMigalastat was administered orally during the 12-week treatment period and then during the optional 2 treatment extension periods. Treatment Period: * Migalastat 25 mg BID for Weeks 1 and 2 (Day 1 through the morning dose on Day 14). * Migalastat 100 mg BID for Weeks 3 and 4 (Day 15 through the morning dose on Day 28). * Migalastat 250 mg BID for Weeks 5 and 6 (Day 29 through the morning dose on Day 42). * Migalastat 25 mg BID for Weeks 6 to 12 (Days 43 to 84). Extension Period: * Migalastat 25 mg BID for Weeks 12 through 48. * Migalastat 50 mg QD for Weeks 48 through 96. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Males between 18 and 55 years of age (inclusive)
- Hemizygous for Fabry disease
- Had a confirmed diagnosis of Fabry disease with a documented missense gene mutation (individual or familial)
- Had enhanceable enzyme activity
- In the judgment of the investigator, were either able to safely suspend ERT throughout the study, or be ERT naive
Key exclusion criteria (7 listed)
- 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)
- History of organ transplant
- Serum creatinine >2 mg per deciliter on Day -2
- Screening 12-lead electrocardiogram demonstrating corrected QT interval >450 milliseconds prior to dosing
- Taking a medication prohibited by the protocol: Fabrazyme® (agalsidase beta), Replagal™ (agalsidase alfa), Glyset® (miglitol), Zavesca® (miglustat), or any experimental therapy for any indication
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 |
Primary outcome
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
Time frame: Day 1 (after dosing) through Week 96
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 96 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 hr (postdose)
α-Galactosidase A (α-Gal A) Activity In Leukocytes At Baseline, Week 12, And Week 96
Time frame: Baseline, Week 12 (end of treatment period), Week 96 (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 30 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.
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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
5 sites in 1 country: 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 5 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 7 inclusion and 7 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 30 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 5 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 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 96). 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 NCT00214500, 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 30 Oct 2018; AzTrials last refreshed its copy on 8 Nov 2026.