Dose-ranging Study of PRX-102 in Adult Fabry Disease Patients

NCT01678898 | Completed Phase 1 Results

• 1 other identifier: PB-102-F01 & PB-102-F02
• Study Type: interventional
• Target: 18
• Locations: 6 countries
• Sites: 14

Brief Summary

This is the first human treatment with PRX-102, an enzyme being developed as a long-term enzyme replacement therapy in patients with a confirmed diagnosis of Fabry disease (alpha galactosidase deficiency). The safety, tolerability, and exploratory efficacy will be evaluated in this study of increasing doses. Patients will be treated with infusions every two weeks for 12 months.

Conditions

Fabry Disease

Keywords

Fabry disease; Alpha galactosidase deficiency; Metabolic storage disease

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  Reportings of adverse events reported by the patient and from monitoring with clinical laboratory, physical examination and ECG. Results represent the number of AEs that were considered possibly, probably, or definitely related to treatment.

  12 months

Other Outcomes (23)

• Plasma Gb3 Concentrations

  Plasma Gb3 concentration (ug/mL) was measured at baseline and every 3 months up to 12 months.

• Kidney Function - Change in eGFR

  eGFR is performed at baseline (day 1) weeks 4, 8, 12, 26, 38 and 52 (12 months)

• Plasma Lyso-Gb3 Levels

  Plasma Lyso-Gb3 concentration (ng/mL) was measured at baseline and every 3 months up to 12 months.

Study Arms (3)

0.2 mg/kg

EXPERIMENTAL

PRX-102 0.2 mg/kg every 2 weeks

Drug: PRX-102

1 mg/kg

EXPERIMENTAL

PRX-102 1 mg/kg every 2 weeks

Drug: PRX-102

2 mg/kg

EXPERIMENTAL

PRX-102 2 mg/kg every 2 weeks

Drug: PRX-102

Interventions

PRX-102 DRUG

Also known as: plant cell expressed recombinant human alpha-galactosidase-A

0.2 mg/kg; 1 mg/kg; 2 mg/kg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptomatic adult Fabry patients (≥18 yrs)
• Males: plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than lower limit of normal (LLN in plasma=3.2 nmol/hr/ml, LLN in leucocytes=32 nmol/hr/mg/protein)
• Females: historical genetic test results consistent with Fabry mutations
• Globotriaosylceramide (Gb3) concentration in urine \> 1.5 times upper normal limit
• Patients who have never received enzyme replacement therapy (ERT) in the past, or patients who have not received ERT in the past 6 months and have a negative anti alpha galactosidase antibody test
• eGFR ≥ 60 mL/min/1.73m2
• The patient signs informed consent
• Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically acceptable method of contraception, not including the rhythm method

You may not qualify if:

• Participation in any trial of an investigational drug within 30 days prior to study screening
• Chronic kidney disease stages 3-5 (CKD 3-5) (Appendix 7)
• History of dialysis or renal transplantation
• Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening
• Severe myocardial fibrosis by MRI (≥2 late-enhancement \[LE\] positive left ventricular segments) (Weidemann et al. 2009)
• History of clinical stroke
• Pregnant or nursing
• Presence of HIV and/or HBsAg and/or Hepatitis C infections
• Known allergies to ERT
• Known allergy to Gadolinium based contrast agents
• 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
• Chiesi Farmaceutici S.p.A.: collaborator

Study Sites (14)

UC Davis Medical Center, MIND Institute Department of Pediatrics, Section of Genetics

Sacramento, California, 95817, United States

Location

Department of Human Genetics, Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

University of Iowa Health Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Research Baylor Institute of Metabolic Disease

Dallas, Texas, 75226, United States

Location

O & O Alpan LLC

Fairfax, Virginia, 22030, United States

Location

Royal Melbourne Hospital

Victoria Park, 3050, Australia

Location

Hematology and Clinical Research Private Institute

Asunción, Paraguay

Location

Clinical Center of Serbia

Belgrade, Serbia

Location

Hospital de Dia Quiron Zaragoza

Zaragoza, 50012, Spain

Location

The Royal Free Hospital

London, NW3 2QG, United Kingdom

Location

Related Publications (1)

• Schiffmann R, Goker-Alpan O, Holida M, Giraldo P, Barisoni L, Colvin RB, Jennette CJ, Maegawa G, Boyadjiev SA, Gonzalez D, Nicholls K, Tuffaha A, Atta MG, Rup B, Charney MR, Paz A, Szlaifer M, Alon S, Brill-Almon E, Chertkoff R, Hughes D. Pegunigalsidase alfa, a novel PEGylated enzyme replacement therapy for Fabry disease, provides sustained plasma concentrations and favorable pharmacodynamics: A 1-year Phase 1/2 clinical trial. J Inherit Metab Dis. 2019 May;42(3):534-544. doi: 10.1002/jimd.12080. Epub 2019 Apr 8.

  PMID: 30834538 RESULT

MeSH Terms

Conditions

Fabry Disease

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

Results Point of Contact

• Title: Raul Chertkoff
• Organization: Protalix Ltd

raul@protalix.com

+972-4-9028100

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2012
• First Posted: September 5, 2012
• Study Start: October 1, 2012
• Primary Completion: March 6, 2016
• Study Completion: March 6, 2016
• Last Updated: September 13, 2023
• Results First Posted: January 27, 2020

Record last verified: 2023-09

Locations

ES (1); AU (1); US (9); PA (1); SE (1); GB (1)