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

Primary Purpose

Fabry Disease

Status

Withdrawn

Phase

Phase 3

Locations

Study Type

Interventional

Intervention

PRX-102

Placebo

About this trial

This is an interventional treatment trial for Fabry Disease focused on measuring Gastrointestinal symptoms, Diarrhea, Abdominal pain

Eligibility Criteria

14 Years - 45 Years (Child, Adult)MaleDoes not accept 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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

PRX-102

Placebo

Arm Description

PRX-102 infusions every 2 weeks

Placebo infusions every 2 weeks

Outcomes

Primary Outcome Measures

IBSSS Part 1

Irritable Bowel Syndrome Severity Score

Secondary Outcome Measures

Stool frequency

from BSFS diary

Body Weight

Plasma Lyso-Gb3

Plasma Gb3

Urine Lyso-GB3

Frequency of pain medication use

Full Information

NCT ID

NCT02921620

First Posted

September 26, 2016

Last Updated

January 4, 2018

Sponsor

Protalix

1. Study Identification

Unique Protocol Identification Number

NCT02921620

Brief Title

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

2. Study Status

Record Verification Date

January 2018

Overall Recruitment Status

Withdrawn

Why Stopped

Protocol not feasible

Study Start Date

July 2017 (Anticipated)

Primary Completion Date

July 2018 (Anticipated)

Study Completion Date

July 2018 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Protalix

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Fabry Disease

Keywords

Gastrointestinal symptoms, Diarrhea, Abdominal pain

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PRX-102

Arm Type

Experimental

Arm Description

PRX-102 infusions every 2 weeks

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo infusions every 2 weeks

Intervention Type

Biological

Intervention Name(s)

PRX-102

Other Intervention Name(s)

pegunigalsidase alfa, recombinant human alpha galactosidase-A

Intervention Description

Intravenous

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Intravenous

Primary Outcome Measure Information:

Title

IBSSS Part 1

Description

Irritable Bowel Syndrome Severity Score

Time Frame

Every 2 weeks for 6 months

Secondary Outcome Measure Information:

Title

Stool frequency

Description

from BSFS diary

Time Frame

After every bowel movement for 6 months

Title

Body Weight

Time Frame

Every 2 weeks for 6 months

Title

Plasma Lyso-Gb3

Time Frame

Every 4 weeks for 6 months

Title

Plasma Gb3

Time Frame

Every 4 weeks for 6 months

Title

Urine Lyso-GB3

Time Frame

Every 6 weeks for 6 months

Title

Frequency of pain medication use

Time Frame

Every 2 weeks for 6 months

Other Pre-specified Outcome Measures:

Title

Anti-PRX-102 antibodies

Time Frame

Every 4 weeks for 6 months

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

14 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Raul Chertkoff, MD

Organizational Affiliation

Protalix Ltd.

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Undecided

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

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