A Study of AT2101 (Afegostat Tartrate) in Adult Patients With Type 1 Gaucher Disease Currently Receiving Enzyme Replacement Therapy

Study Overview
=================
Brief Summary
-----------------
This study was conducted to test the safety and tolerability of afegostat tartrate in participants with type 1 Gaucher disease already receiving enzyme replacement therapy.

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 14-day screening period, a 28-day treatment period, and a 7-day wash-out period. Participants received 1 of 4 dosing regimens for afegostat tartrate.

Official Title
-----------------
A Randomized, Open-label Study to Assess the Safety and Tolerability of Multiple Dose Levels and Multiple Dosing Regimens of AT2101 in Adult Patients With Type 1 Gaucher Disease Currently Receiving Enzyme Replacement Therapy

Conditions
-----------------
Gaucher Disease, Type 1, Type 1 Gaucher Disease, Gaucher Disease

Intervention / Treatment
-----------------
* Drug: Afegostat tartrate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Had a confirmed diagnosis of type 1 Gaucher disease with a known documented missense gene mutation in at least 1 of the 2 gene-encoding β-glucosidase alleles Clinically stable Male or female participants, 18 to 74 years old inclusive All participants of childbearing potential used adequate birth control Provided written informed consent to participate in the study Exclusion Criteria: Clinically significant disease, severe complications from Gaucher disease, or serious illness that precluded participation in the study in the opinion of the Investigator that compromised the safety of the participant or precluded the participant from completing the study During the screening period, any clinically significant findings, as deemed by the Investigator Partial or total splenectomy (removal of spleen) within the 2 years prior to study entry History of pulmonary hypertension or Gaucher related lung disease History of allergy or sensitivity to the study drug or any excipients, including any prior serious adverse reaction to iminosugars (for example, N-butyldeoxynojirimycin or miglustat) Pregnant or breast-feeding Current/recent drug or alcohol abuse Treatment with any investigational product in the 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 or symptoms of gastrointestinal, liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Afegostat tartrate 25 milligrams (mg) once per day<br>Afegostat tartrate was administered orally during the 4-week treatment period. | Drug: Afegostat tartrate<br> <br> * Other names: AT2101;|
| Experimental: Afegostat tartrate 150 mg once per day<br>Afegostat tartrate was administered orally once per day during the 4-week treatment period. | Drug: Afegostat tartrate<br> <br> * Other names: AT2101;|
| Experimental: Afegostat tartrate 150 mg once every four days<br>Afegostat tartrate was administered orally once every 4 days during the 4-week treatment period. | Drug: Afegostat tartrate<br> <br> * Other names: AT2101;|
| Experimental: Afegostat tartrate 150 mg once every seven days<br>Afegostat tartrate was administered orally once every 7 days during the 4-week treatment period. | Drug: Afegostat tartrate<br> <br> * Other names: AT2101;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number Of Participants Who Experienced Severe Treatment-emergent Adverse Events (TEAEs) | TEAEs were defined as any adverse event (AE) with a start date on or after administration of the study drug (on Day 1). A severe AE was 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 7 days after the last dose of study drug (Day 35) is presented. A summary of serious and all other non-serious AEs regardless of causality is located in the Reported Adverse Events module. | Day 1 (after dosing) through Day 35 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline To End Of Treatment In Beta-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. | Baseline, Day 28 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
afegostat tartrate, isofagomine tartrate, AT2101, Amicus Therapeutics