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

• ClinicalTrials.gov Identifier: NCT01747980
• Recruitment Status: Completed
• First Posted: December 12, 2012
• Last Update Posted: April 7, 2014
• Sponsor: Protalix
• Information provided by (Responsible Party): Protalix

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Gaucher Disease	Drug: PRX-112	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: March 2013
• Actual Primary Completion Date: January 2014
• Actual Study Completion Date: March 2014

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

1. Adverse Events [ Time Frame: 3 days after the last dose ]
   Spontaneous reports of adverse events, or events identified during physical examination or clinical laboratory testing

Secondary Outcome Measures :

1. Area Under the Curve (AUC) [ Time Frame: From start of infusion to 30 hours after infusion ]
   Area under the GCD level curve 0-30 hours (AUC0-30h)
2. Maximum Concentration (Cmax) [ Time Frame: From start of infusion to 30 hours after infusion ]
3. Time of maximum prGCD concentration (Tmax) [ Time Frame: From start of infusion to 30 hours after infusion ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• Responsible Party: Protalix
• ClinicalTrials.gov Identifier: NCT01747980
• Other Study ID Numbers: PB-112-01
• First Posted: December 12, 2012
• Last Update Posted: April 7, 2014
• Last Verified: April 2014

Keywords provided by Protalix:

Gaucher disease; human glucocerebrosidase; plant recombinant human glucocerebrosidase

Additional relevant MeSH terms:

Gaucher Disease; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Lipid Metabolism Disorders