A Phase III Trial to Assess the Safety and Efficacy of Plant Cell Expressed GCD in Patients With Gaucher Disease

• Change From Baseline in Liver Volume [ Time Frame: Baseline and 9 months ]
  Calculated as percent change in liver volume from Baseline to 9 months
• Change in Hemoglobin [ Time Frame: Baseline and Month 9 ]
  Absolute change in Hemoglobin concentration from Baseline to Month 9
• Change in Platelet Count [ Time Frame: Baseline and Month 9 ]
  Change in Platelet count from Baseline to Month 9

Gaucher disease, the most prevalent lysosomal storage disorder, is caused by mutations in the human glucocerebrosidase gene (GCD) leading to reduced activity of the lysosomal enzyme glucocerebrosidase and thereby to the accumulation of substrate glucocerebroside (GlcCer) in the cells of the monocyte-macrophage system.

This is the second trial to utilize a recombinant active form of lysosomal enzyme, glucocerebrosidase, (human prGCD) which is expressed and purified in a bioreactor system from transformed carrot plant root cell line.

This will be a multi-center, randomized, double-blind, parallel group, dose-ranging trial to assess the safety and efficacy of prGCD in 30 untreated patients with Gaucher disease. Patients will receive IV infusion of prGCD every two weeks at the selected medical center. The duration of the study will be nine months. At the end of the 9-month treatment period (20 visits, 38 weeks) eligible patients will be offered enrollment in an open-label extension study.

There will be two treatment groups, 15 patients in each treatment group.

Treatment Group I: 30 units/kg every 2 weeks. Treatment Group II: 60 units/kg every 2 weeks.

All patients will have pharmacokinetic data collected over approximately 3 hours with frequent blood samples following the first and final doses of prGCD.

• Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD)
  Intravenous infusion every two weeks for 9 months
  Other Name: Taliglucerase alfa
• Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD)
  Intravenous infusion every 2 weeks for 9 months
  Other Name: Taliglucerase alfa

• Experimental: prGCD 30 Units/kg
  Intervention: Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD)
• Experimental: prGCD 60 Units/kg
  Intervention: Drug: Plant cell expressed recombinant glucocerebrosidase (prGCD)

• Abbas R, Park G, Damle B, Chertkoff R, Alon S. Pharmacokinetics of Novel Plant Cell-Expressed Taliglucerase Alfa in Adult and Pediatric Patients with Gaucher Disease. PLoS One. 2015 Jun 8;10(6):e0128986. doi: 10.1371/journal.pone.0128986. eCollection 2015.
• Zimran A, Brill-Almon E, Chertkoff R, Petakov M, Blanco-Favela F, Muñoz ET, Solorio-Meza SE, Amato D, Duran G, Giona F, Heitner R, Rosenbaum H, Giraldo P, Mehta A, Park G, Phillips M, Elstein D, Altarescu G, Szleifer M, Hashmueli S, Aviezer D. Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease. Blood. 2011 Nov 24;118(22):5767-73. doi: 10.1182/blood-2011-07-366955. Epub 2011 Sep 6. Erratum in: Blood. 2012 May 10;119(19):4577.
• Winckler T. [Enzyme replacement therapy for Gaucher's Disease]. Pharm Unserer Zeit. 2008;37(5):352-3. doi: 10.1002/pauz.200890067. German.

Inclusion Criteria:

• Males and females, 18 years or older
• Confirmed enzymatic diagnosis of Gaucher disease
• Splenomegaly defined as greater than eight times the expected volume (measured volume divided by estimated volume (0.2% of body weight)] as determined by MRI volumetric analysis
• Female patients of child-bearing potential who agree to use a medically acceptable method of contraception
• Thrombocytopenia (defined as platelet counts below the lower limit of normal) and/or anemia (defined by hemoglobin level at least 1 g/dL below normal range according to sex and age).
• Patients who have not received ERT in the past or patients whoc have not received ERT in the past 12 months and have a negative anti-glucocerebrosidase antibody test.
• Patients who have not received substrate reduction therapy (SRT) in the past 12 months.
• Ability to provide a written informed consent.

Exclusion Criteria:

• Currently taking another experimental drug for any condition
• Pregnant or nursing
• Presence of HIV and/or, HBsAg and/or hepatitis C infections
• Presence of severe neurological signs and symptoms, defined as complete ocular paralysis, overt myoclonus or history of seizures, characteristic of neuronopathic Gaucher disease.
• Previous anaphylactoid reaction to Cerezyme® or Ceredase®.
• History of allergy to carrots.