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

NCT02921620 | Withdrawn Phase 3 FDA Drug

• 1 other identifier: PB-102-F10
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Fabry Disease

Keywords

Gastrointestinal symptoms; Diarrhea; Abdominal pain

Outcome Measures

Primary Outcomes (1)

• IBSSS Part 1

  Irritable Bowel Syndrome Severity Score

  Every 2 weeks for 6 months

Secondary Outcomes (6)

• Stool frequency

  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

Other Outcomes (1)

• Anti-PRX-102 antibodies

  Every 4 weeks for 6 months

Study Arms (2)

PRX-102

EXPERIMENTAL

PRX-102 infusions every 2 weeks

Biological: PRX-102

Placebo

PLACEBO COMPARATOR

Placebo infusions every 2 weeks

Other: Placebo

Interventions

PRX-102 BIOLOGICAL

Intravenous

Also known as: pegunigalsidase alfa, recombinant human alpha galactosidase-A

PRX-102

Placebo OTHER

Intravenous

Placebo

Eligibility Criteria

• Age: 14 Years - 45 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Protalix: lead

MeSH Terms

Conditions

Fabry Disease; Diarrhea; Abdominal Pain

Condition Hierarchy (Ancestors)

Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Vascular Diseases; Cardiovascular Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations

Study Officials

• Raul Chertkoff, MD

  Protalix Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2016
• First Posted: October 3, 2016
• Study Start: July 1, 2017
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: January 8, 2018

Record last verified: 2018-01