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

Protalix BioTherapeutics

Status and phase

Withdrawn

Phase 3

Conditions

Fabry Disease

Treatments

Biological: PRX-102

Other: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT02921620

PB-102-F10

Details and patient eligibility

About

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.

Sex

Male

Ages

14 to 45 years old

Volunteers

No Healthy Volunteers

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