Study to Evaluate the Safety and EffIcacy of PRX-102 on Gastrointestinal Symptoms in Naïve Fabry Disease

Study Overview
=================
Brief Summary
-----------------
The study will be a randomized, double blind, placebo-controlled study of the safety and efficacy of PRX-102 in ERT naïve male patients randomized 1:1. Patient age will be 14 to 45 years. Patients must have diarrhea defined as ≥ 3 stools a day with an average consistency of ≥ 5.5 on the Bristol Stool Form Scale (BSFS) by patient electronic diary and moderate to severe gastrointestinal symptoms as defined by the Irritable Bowel Symptom Severity Score (IBSSS) Part 1 average > 175 derived from at least two IBSSS assessments during screening period. Patients will receive intravenous infusions of PRX-102 1 mg/kg or placebo every two weeks for 6 months.

Official Title
-----------------
A Randomized, Double Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of PRX-102 on Gastrointestinal Symptoms in Naïve Fabry Disease Patients

Conditions
-----------------
Fabry Disease

Intervention / Treatment
-----------------
* Biological: PRX-102
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males, age 14-45 years, naïve to enzyme replacement therapy (ERT) or off ERT or off chaperone treatment for at least 6 months and negative for anti-PRX-102 antibodies A documented diagnosis of Fabry disease: Plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than lower limit of normal (LLN) eGFR by CKD-EPI > 30 ml/min/1.73 m2 Moderate to severe gastrointestinal symptoms as defined by: Average score of > 175 from at least two Irritable Bowel Symptom Severity Score (IBSSS) Part 1 assessments before randomization. Average stool consistency of ≥ 5.5 on the Bristol Stool Form Scale (BSFS) by patient diary during 2 weeks prior to randomization out of the 4 week of screening period and ≥ 3 stools a day with a consistency of ≥ 5 on the BSFS during the week before randomization. Completed electronic BSFS diary on at least 6 of the 7 days during the week prior to randomization AND at least 11 of the 14 days during the 2 weeks prior to randomization. Exclusion Criteria: Patients will be evaluated to rule out other gastrointestinal comorbidity than Fabry disease as responsible for the gastrointestinal symptoms by: i. Medical History for non Fabry gastrointestinal comorbidity ii. Occult blood in stool iii. Stool culture for bacteria and parasites iv. Calprotectin in stool v. Sigmoidoscopy Use of any kind of laxatives Initiation of anti-diarrheal medications during the screening period History of renal dialysis or transplantation Use of, or change in dose of, angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) for less than 4 weeks prior to screening Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period before randomization Congestive heart failure NYHA Class IV Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before randomization Known history of hypersensitivity to Gadolinium contrast agent Known allergies to ERT Presence of any medical, emotional, behavioral or psychological condition that, in the judgment of the Investigator and/or Medical Director, would interfere with the patient's compliance with the requirements of the study

Ages Eligible for Study
-----------------
Minimum Age: 14 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Male

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PRX-102<br>PRX-102 infusions every 2 weeks | Biological: PRX-102<br>* Intravenous<br>* Other names: recombinant human alpha galactosidase-A;|
| Placebo Comparator: Placebo<br>Placebo infusions every 2 weeks | Other: Placebo<br>* Intravenous<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| IBSSS Part 1 | Irritable Bowel Syndrome Severity Score | Every 2 weeks for 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stool frequency | from BSFS diary | After every bowel movement for 6 months | 
| Body Weight |  | Every 2 weeks for 6 months | 
| Plasma Lyso-Gb3 |  | Every 4 weeks for 6 months | 
| Plasma Gb3 |  | Every 4 weeks for 6 months | 
| Urine Lyso-GB3 |  | Every 6 weeks for 6 months | 
| Frequency of pain medication use |  | Every 2 weeks for 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Gastrointestinal symptoms, Diarrhea, Abdominal pain