Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Safety and Pharmacokinetics of Oral PRX-112 in Gaucher Disease Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Protalix
ClinicalTrials.gov Identifier:
NCT01747980
First received: December 5, 2012
Last updated: April 4, 2014
Last verified: April 2014
  Purpose

Absorption of therapeutic proteins taken orally has remained the major hurdle for treatment in humans. The proteins are generally degraded by enzymes in the stomach and intestine and the intestine lining that prevents absorption into the circulation. Administration of PRX-112, a plant recombinant human glucocerebrosidase (prGCD) using plant cells as carrier vehicle, may help overcome many of these hurdles. The plant cell wall protects the protein from degradation in its transport through the upper GI and allows release in the lower intestine. Studies in animals have shown that prGCD delivered in this way can be found in the blood stream in an active form.


Condition Intervention Phase
Gaucher Disease
Drug: PRX-112
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Exploratory, Open-label Study to Evaluate the Safety of PRX-112 and Pharmacokinetics of Oral prGCD (Plant Recombinant Human Glucocerebrosidase) in Gaucher Patients

Resource links provided by NLM:


Further study details as provided by Protalix:

Primary Outcome Measures:
  • Adverse Events [ Time Frame: 3 days after the last dose ] [ Designated as safety issue: Yes ]
    Spontaneous reports of adverse events, or events identified during physical examination or clinical laboratory testing


Secondary Outcome Measures:
  • Area Under the Curve (AUC) [ Time Frame: From start of infusion to 30 hours after infusion ] [ Designated as safety issue: No ]
    Area under the GCD level curve 0-30 hours (AUC0-30h)

  • Maximum Concentration (Cmax) [ Time Frame: From start of infusion to 30 hours after infusion ] [ Designated as safety issue: No ]
  • Time of maximum prGCD concentration (Tmax) [ Time Frame: From start of infusion to 30 hours after infusion ] [ Designated as safety issue: No ]

Enrollment: 16
Study Start Date: March 2013
Study Completion Date: March 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: PRX-112
250 mL of resuspended carrot cells administered orally in a vehicle
Drug: PRX-112
Single dose level, four doses per cohort
Other Name: plant expressed recombinant human glucocerebrosidase

Detailed Description:

This exploratory, open-label safety and pharmacokinetic (PK) study is designed to assess the delivery of prGCD after oral administration of PRX-112 in Gaucher subjects. Subjects will receive an oral dose of PRX-112 in a single administration and followed by 3 consecutive daily administrations at the same dose. prGCD levels in plasma will be determined at selected time points. Safety parameters will also be assessed at selected time points. Enrollment will proceed into the next dosage cohort after the pharmacokinetic and safety data of the previous cohort have been reviewed. A different dosage may be selected based on the pharmacokinetic results of the first cohort.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females, 18 years or older.
  • Historical diagnosis of Gaucher disease with leukocyte GCD activity level ≤3 nmol/mg*hr (≤30 % of the mean activity of the reference range)
  • Subjects who have not received enzyme replacement therapy (ERT) or substrate replacement therapy (SRT) in the past or patients who have not received ERT in the past twelve months
  • Body Mass Index (BMI) 19 to 25 kg/m2 (inclusive).
  • Non-smoking (by declaration) for a period of at least 6 months prior to screening visit.
  • Subjects in generally good health in the opinion of the investigator as determined by medical history, vital signs and a physical examination.
  • Negative hepatitis B or hepatitis C serology tests at screening.
  • Ability to provide a written informed consent
  • Female subjects of child-bearing potential or male subjects with female partners of child-bearing potential must agree to use two methods of contraception, one of which must be a barrier method. Acceptable methods of contraception include hormonal products, intrauterine device, or male or female condoms.

Exclusion Criteria:

  • Presence of any co-morbidity other than Gaucher Disease
  • Presence of any GIT disease or symptomatology suspected to be GIT related using a study specific GI questionnaire
  • Subjects with any history of allergic response to drugs or other allergies deemed clinically significant or exclusionary for the study, including known food allergies
  • History of alcohol or drug abuse
  • Subjects who donated blood in the three months, or received blood or plasma derivatives in the six months, preceding study drug administration.
  • Use of any investigational drug at screening or within 3 months of dosing.
  • Subjects with an inability to communicate well with the investigators and study staff (i.e., language problem, poor mental development or impaired cerebral function).
  • Subjects who are non-cooperative or unwilling to sign the consent form.
  • Pregnant or nursing or planning to be pregnant during the study period.
  • Have used any medication (excluding paracetamol), within 7 days of study drug administration including laxatives or other drugs, teas or food additives known to be used to treat constipation or diarrhea.
  • Presence of any medical, emotional, behavioral or psychological condition that in the judgment of the investigator would interfere with the subject's compliance with the requirements of the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01747980

Locations
Israel
Rambam Medical Center
Haifa, Israel, 31096
Shaare Zedek Medical Center
Jerusalem, Israel, 91031
Sponsors and Collaborators
Protalix
Investigators
Study Chair: Einat Almon, PhD Protalix Ltd
  More Information

No publications provided

Responsible Party: Protalix
ClinicalTrials.gov Identifier: NCT01747980     History of Changes
Other Study ID Numbers: PB-112-01
Study First Received: December 5, 2012
Last Updated: April 4, 2014
Health Authority: Israel: Ministry of Health

Keywords provided by Protalix:
Gaucher disease
human glucocerebrosidase
plant recombinant human glucocerebrosidase

Additional relevant MeSH terms:
Gaucher Disease
Brain Diseases
Brain Diseases, Metabolic
Brain Diseases, Metabolic, Inborn
Central Nervous System Diseases
Genetic Diseases, Inborn
Lipid Metabolism Disorders
Lipid Metabolism, Inborn Errors
Lipidoses
Lysosomal Storage Diseases
Lysosomal Storage Diseases, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Sphingolipidoses

ClinicalTrials.gov processed this record on November 20, 2014