Gaucher DiseasePhase 2NCT00446550
A Study of Oral AT2101 (Afegostat Tartrate) in Treatment-naive Patients With Gaucher Disease
A Phase 2 study testing afegostat tartrate in people with Gaucher Disease and Type 1 Gaucher Disease, run by Amicus Therapeutics at 11 sites in 4 countries.
Trial summary
This study evaluated the safety and tolerability of afegostat tartrate in participants with type 1 Gaucher disease who were not receiving enzyme replacement therapy (ERT) or substrate reduction therapy (SRT). Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Gaucher Disease, Type 1 Gaucher Disease, Gaucher Disease, Type 1
- What is being tested?
- afegostat tartrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 11 sitesin 4 countries
- Study dates
- 11 Jun 2008to 20 Aug 2009
- 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 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of type 1 Gaucher disease with a known genotype and a documented missense gene mutation in at least 1 of the 2 gene-encoding β-glucosidase (GBA) alleles
- Clinically stable
- Treatment naïve to ERT and SRT or had not received ERT or SRT in the 12 months before screening
- Willing to not initiate ERT or SRT treatment during study participation
- Male or female participants, 18 to 74 years old, inclusive
- At the screening period (Day -21 to Day -1), participants must have met at least 2 of the following criteria: platelet count of ≤150,000 per microliter, hemoglobin ≤12 grams/deciliter (g/dL) for females and ≤13 g/dL for males, liver volume ≥1.25 multiples of normal (MN), and spleen volume ≥2 MN
- All participants of reproductive potential were required to practice an acceptable method of contraception
- Provided written informed consent to participate in the study
Who cannot join
- A clinically significant disease other than Gaucher disease, severe complications from Gaucher disease, or serious intercurrent illness that precluded participation in the study in the opinion of the investigator
- During the screening period, had any clinically significant findings as deemed by the investigator
- Partial or total splenectomy
- Documentation of moderate or severe pulmonary hypertension, defined as pulmonary arterial pressure >35 millimeters of mercury (mmHg) or significant Gaucher-related lung disease
- History of allergy or sensitivity to the study drug or any excipients, including any prior serious allergic reaction to iminosugars
- Pacemaker or other contraindication for magnetic resonance imaging (MRI) scanning
Show all 11Show fewer
- Pregnant or breast-feeding
- Current/recent drug or alcohol abuse
- Treatment with any investigational product in the last 90 days before study entry
- Treatment in the previous 90 days with any drug known to have a well-defined potential for toxicity to a major organ
- Presence of symptoms of gastrointestinal, liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
Trial locations and contacts
11 sites in 4 countries.
11 sites in 4 countries
United States7 sites
Study site
Beverly Hills, California, 90211
Study site
Boston, Massachusetts, 02114
Study site
Cincinnati, Ohio, 45229
Study site
Coral Springs, Florida, 33065
Study site
Decatur, Georgia, 30033
Study site
Iowa City, Iowa, 52242
Study site
Kansas City, Kansas, 66160
About this study
Official title: A Randomized, Open-label Study To Assess the Safety and Tolerability of AT2101 in Treatment-naive Adult Patients With Type 1 Gaucher Disease
This study evaluated the safety and tolerability of afegostat tartrate in participants with type 1 Gaucher disease who were not receiving enzyme replacement therapy (ERT) or substrate reduction therapy (SRT).
Read the detailed description
This was a Phase 2, open-label study in participants with Gaucher disease, a lysosomal storage disorder. Afegostat tartrate (also known as AT2101 or isofagomine tartrate) is designed to act as a pharmacological chaperone by selectively binding to misfolded β-glucocerebrosidase (GCase) and helping it fold correctly, intended to restore GCase activity. The study consisted of a 21-day screening period, a 24-week treatment period, and follow-up visit (Day 183, end-of-study). Participants were randomized in a 1:1 ratio to 1 of 2 treatment regimens for afegostat tartrate (3 days on treatment/4 days off or 7 days on treatment/7 days off).
- Being tested
- afegostat tartrate
- Keywords
- Amicus Therapeutics, afegostat tartrate, isofagomine tartrate, AT2101
- Medical subject headings
- Gaucher Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
afegostat tartrateDrug
Also called isofagomine tartrate, AT2101
| Study group | Role | What they receive |
|---|---|---|
| Afegostat Tartrate Treatment Regimen 1 | Experimental | For the first 2 weeks, afegostat tartrate was administered orally at a dose of 225 milligrams (mg) once daily (QD) for 7 consecutive days, followed by no study medication for 7 consecutive days. After 2 weeks, participants then took 225 mg afegostat tartrate QD for 3 consecutive days, followed by no study medication for 4 consecutive days. This 3-days-on/4-days-off treatment regimen was followed for 22 weeks. Receives: Drug: afegostat tartrate |
| Afegostat Tartrate Treatment Regimen 2 | Experimental | Afegostat tartrate was administered orally at a dose of 225 mg QD for 7 consecutive days, followed by no study medication for 7 consecutive days. This 7-days-on/7-days-off treatment regimen was followed for 24 weeks. Receives: Drug: afegostat tartrate |
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)
A TEAE was defined as any adverse event (AE) 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 AE defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced 1 or more severe TEAEs after dosing on Day 1 through the end of follow-up (Day 183) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
Measured: Day 1 (after dosing) through Day 183
Secondary outcomes (1)
Change From Baseline To End Of Treatment In β-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC)
GCase is a biomarker used to assess the PD effects of afegostat tartrate. Blood samples were collected to assess GCase levels in WBC. The baseline value was defined as the last non-missing value before the start of study drug.
Measured: Baseline, Day 169
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2007 (estimated)
- Study start11 Jun 2008
- Primary completion20 Aug 2009
- Study completion20 Aug 2009
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.
- Other trials for Gaucher 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
- 19 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
- NCT00446550
- Sponsor's protocol ID
- GAU-CL-202
- Status last verified
- Jul 2018
- First submitted
- 9 Mar 2007
- Last updated
- 15 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label Study To Assess the Safety and Tolerability of AT2101 in Treatment-naive Adult Patients With Type 1 Gaucher Disease
- ClinicalTrials.gov ID
- NCT00446550
- Acronym / sponsor ID
- GAU-CL-202
- Keywords
- Amicus Therapeutics, afegostat tartrate, isofagomine tartrate, AT2101
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Amicus TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 11 Jun 2008 (actual)
- Primary completion
- 20 Aug 2009 (actual)
- Study completion
- 20 Aug 2009 (actual)
- First posted
- 13 Mar 2007 (estimated)
- Results
- Posted 15 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluated the safety and tolerability of afegostat tartrate in participants with type 1 Gaucher disease who were not receiving enzyme replacement therapy (ERT) or substrate reduction therapy (SRT).
Detailed description
This was a Phase 2, open-label study in participants with Gaucher disease, a lysosomal storage disorder. Afegostat tartrate (also known as AT2101 or isofagomine tartrate) is designed to act as a pharmacological chaperone by selectively binding to misfolded β-glucocerebrosidase (GCase) and helping it fold correctly, intended to restore GCase activity. The study consisted of a 21-day screening period, a 24-week treatment period, and follow-up visit (Day 183, end-of-study). Participants were randomized in a 1:1 ratio to 1 of 2 treatment regimens for afegostat tartrate (3 days on treatment/4 days off or 7 days on treatment/7 days off).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Afegostat Tartrate Treatment Regimen 1 | Experimental | Drug: afegostat tartrateFor the first 2 weeks, afegostat tartrate was administered orally at a dose of 225 milligrams (mg) once daily (QD) for 7 consecutive days, followed by no study medication for 7 consecutive days. After 2 weeks, participants then took 225 mg afegostat tartrate QD for 3 consecutive days, followed by no study medication for 4 consecutive days. This 3-days-on/4-days-off treatment regimen was followed for 22 weeks. |
| Afegostat Tartrate Treatment Regimen 2 | Experimental | Drug: afegostat tartrateAfegostat tartrate was administered orally at a dose of 225 mg QD for 7 consecutive days, followed by no study medication for 7 consecutive days. This 7-days-on/7-days-off treatment regimen was followed for 24 weeks. |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Confirmed diagnosis of type 1 Gaucher disease with a known genotype and a documented missense gene mutation in at least 1 of the 2 gene-encoding β-glucosidase (GBA) alleles
- Clinically stable
- Treatment naïve to ERT and SRT or had not received ERT or SRT in the 12 months before screening
- Willing to not initiate ERT or SRT treatment during study participation
- Male or female participants, 18 to 74 years old, inclusive
Key exclusion criteria (11 listed)
- A clinically significant disease other than Gaucher disease, severe complications from Gaucher disease, or serious intercurrent illness that precluded participation in the study in the opinion of the investigator
- During the screening period, had any clinically significant findings as deemed by the investigator
- Partial or total splenectomy
- Documentation of moderate or severe pulmonary hypertension, defined as pulmonary arterial pressure >35 millimeters of mercury (mmHg) or significant Gaucher-related lung disease
- History of allergy or sensitivity to the study drug or any excipients, including any prior serious allergic reaction to iminosugars
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 |
|---|---|---|
| afegostat tartrateAlso: isofagomine tartrate, AT2101 | Drug | Afegostat Tartrate Treatment Regimen 1, Afegostat Tartrate Treatment Regimen 2 |
Primary outcome
Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs)
Time frame: Day 1 (after dosing) through Day 183
A TEAE was defined as any adverse event (AE) 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 AE defined as an AE that was incapacitating and required medical intervention. The number of participants who experienced 1 or more severe TEAEs after dosing on Day 1 through the end of follow-up (Day 183) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module.
1 secondary outcome
Change From Baseline To End Of Treatment In β-glucocerebrosidase (GCase) Levels In White Blood Cells (WBC)
Time frame: Baseline, Day 169
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
11 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing afegostat tartrate in people with Gaucher Disease and Type 1 Gaucher Disease, run by Amicus Therapeutics at 11 sites in 4 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 8 inclusion and 11 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 15 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Israel, South Africa, United Kingdom. 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 15 Aug 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 Day 183). 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 15 Aug 2018.