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

NCT01747980 | Completed Phase 1

• 1 other identifier: PB-112-01
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

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.

Conditions

Gaucher Disease

Keywords

Gaucher disease; human glucocerebrosidase; plant recombinant human glucocerebrosidase

Outcome Measures

Primary Outcomes (1)

• Adverse Events

  Spontaneous reports of adverse events, or events identified during physical examination or clinical laboratory testing

  3 days after the last dose

Secondary Outcomes (3)

• Area Under the Curve (AUC)

  From start of infusion to 30 hours after infusion

• Maximum Concentration (Cmax)

  From start of infusion to 30 hours after infusion

• Time of maximum prGCD concentration (Tmax)

  From start of infusion to 30 hours after infusion

Study Arms (1)

PRX-112

EXPERIMENTAL

250 mL of resuspended carrot cells administered orally in a vehicle

Drug: PRX-112

Interventions

PRX-112 DRUG

Single dose level, four doses per cohort

Also known as: plant expressed recombinant human glucocerebrosidase

PRX-112

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Protalix: lead

Study Sites (2)

Rambam Medical Center

Haifa, 31096, Israel

Location

Shaare Zedek Medical Center

Jerusalem, 91031, Israel

Location

MeSH Terms

Conditions

Gaucher 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; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Einat Almon, PhD

  Protalix Ltd.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 5, 2012
• First Posted: December 12, 2012
• Study Start: March 1, 2013
• Primary Completion: January 1, 2014
• Study Completion: March 1, 2014
• Last Updated: April 7, 2014

Record last verified: 2014-04

Locations

IL (2)