Clinical trial NCT02921620: Study to Evaluate the Safety and EffIcacy of PRX-102 on Gastrointestinal Symptoms in Naïve Fabry Disease
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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Fabry Disease
Keywords: Gastrointestinal symptoms
Diarrhea
Abdominal pain
Lead sponsor: Protalix
Sponsor class: INDUSTRY
First posted: 2016-10-03
Enrollment: 0
Sex: MALE
Minimum age (years): 14
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: IBSSS Part 1
timeFrame: Every 2 weeks for 6 months
Secondary outcomes:
measure: Stool frequency
timeFrame: After every bowel movement for 6 months
measure: Body Weight
timeFrame: Every 2 weeks for 6 months
measure: Plasma Lyso-Gb3
timeFrame: Every 4 weeks for 6 months
measure: Plasma Gb3
timeFrame: Every 4 weeks for 6 months
measure: Urine Lyso-GB3
timeFrame: Every 6 weeks for 6 months
measure: Frequency of pain medication use
timeFrame: Every 2 weeks for 6 months
Other outcomes:
measure: Anti-PRX-102 antibodies
timeFrame: Every 4 weeks for 6 months
Locations:
Study officials:
affiliation: Protalix Ltd.
name: Raul Chertkoff, MD
role: STUDY_DIRECTOR
References: