Fabry Disease
Conditions
Keywords
Gastrointestinal symptoms, Diarrhea, Abdominal pain
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.
Interventions
BIOLOGICALPRX-102
Intravenous
OTHERPlacebo
Intravenous
Sponsors
Protalix
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
14 Years to 45 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| IBSSS Part 1 | Every 2 weeks for 6 months | Irritable Bowel Syndrome Severity Score |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stool frequency | After every bowel movement for 6 months | from BSFS diary |
| Body Weight | Every 2 weeks for 6 months | — |
| Plasma Lyso-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 | — |
| Plasma Gb3 | Every 4 weeks for 6 months | — |
Other
| Measure | Time frame |
|---|---|
| Anti-PRX-102 antibodies | Every 4 weeks for 6 months |
Outcome results
None listed