Study to Evaluate the Safety and EffIcacy of PRX-102 on Gastrointestinal Symptoms in Naïve Fabry Disease
- Conditions
- Fabry Disease
- Interventions
- Other: PlaceboBiological: PRX-102
- Registration Number
- NCT02921620
- Lead Sponsor
- Protalix
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- Male
- Target Recruitment
- Not specified
-
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.
-
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo infusions every 2 weeks PRX-102 PRX-102 PRX-102 infusions every 2 weeks
- Primary Outcome Measures
Name Time Method IBSSS Part 1 Every 2 weeks for 6 months Irritable Bowel Syndrome Severity Score
- Secondary Outcome Measures
Name Time Method Plasma Lyso-Gb3 Every 4 weeks for 6 months Stool frequency After every bowel movement for 6 months from BSFS diary
Plasma Gb3 Every 4 weeks for 6 months Urine Lyso-GB3 Every 6 weeks for 6 months Body Weight Every 2 weeks for 6 months Frequency of pain medication use Every 2 weeks for 6 months