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

NCT ID: NCT01678898

Last Updated: 2023-09-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2016-03-06

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.

Detailed Description

Under the PB-102-F01 study protocol, patients will be enrolled into one of three PRX-102 dosing groups (0.2 mg/kg, 1.0 mg/kg, 2.0 mg/kg) and receive PRX-102 as an intravenous infusion every 2 weeks for 12 weeks (3 months). Patients who finish the PB-102-F01 study will be enrolled in the PB-102-F02 extension study and receive the same dose they had received in the PB-102-F01 study for an additional 38 weeks (9 months).

Conditions

Fabry Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

0.2 mg/kg

PRX-102 0.2 mg/kg every 2 weeks

Group Type: EXPERIMENTAL

PRX-102

Intervention Type: DRUG

1 mg/kg

PRX-102 1 mg/kg every 2 weeks

Group Type: EXPERIMENTAL

PRX-102

Intervention Type: DRUG

2 mg/kg

PRX-102 2 mg/kg every 2 weeks

Group Type: EXPERIMENTAL

PRX-102

Intervention Type: DRUG

Interventions

PRX-102

Intervention Type: DRUG

Other Intervention Names

plant cell expressed recombinant human alpha-galactosidase-A

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chiesi Farmaceutici S.p.A.

INDUSTRY

Sponsor Role: collaborator

Protalix

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Sacramento, California, United States

Department of Human Genetics, Emory University School of Medicine

Atlanta, Georgia, United States

University of Iowa Health Clinics

Iowa City, Iowa, United States

University of Kansas Medical Center

Kansas City, Kansas, United States

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Duke University Medical Center

Durham, North Carolina, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Research Baylor Institute of Metabolic Disease

Dallas, Texas, United States

O & O Alpan LLC

Fairfax, Virginia, United States

Royal Melbourne Hospital

Victoria Park, , Australia

Hematology and Clinical Research Private Institute

Asunción, , Paraguay

Clinical Center of Serbia

Belgrade, , Serbia

Hospital de Dia Quiron Zaragoza

Zaragoza, , Spain

The Royal Free Hospital

London, , United Kingdom

Countries

United States; Australia; Paraguay; Serbia; Spain; United Kingdom

References

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.

Reference Type: RESULT

PMID: 30834538 (View on PubMed)

Other Identifiers

PB-102-F01 & PB-102-F02

Identifier Type: -

Identifier Source: org_study_id

NCT01769001

Identifier Type: -

Identifier Source: nct_alias