Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase III, Multicenter, Randomized, Double-Blind Trial to Assess the Safety and Efficacy of Two Parallel Dose Groups of Plant Cell Expressed Recombinant Human Glucocerebrosidase (prGCD) in Patients With Gaucher Disease
Brief Summary: 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.


Options:
A: Inclusion criteria:

I1. Individuals with IFG and/or IGT, or early diabetes, as defined below.

Glucose tolerance status was determined by a 75 g oral glucose tolerance test (OGTT) that was performed fasting (ie, no consumption of food or beverage other than water for at least 8 hours) at the time of screening for all candidates who were not known to have diabetes. The qualifying OGTT could be obtained up to 4 weeks prior to screening provided that anti-diabetic therapy (if any) remained unchanged between the qualifying OGTT and the screening visit. Two plasma glucose values were drawn during the OGTT - a fasting value (FPG) and a value drawn two hours after the 75 g oral glucose load was administered (postprandial plasma glucose \[PPG\]).

- Impaired glucose tolerance (IGT), defined as a PPG value ≥140 and \<200 mg/dL (ie, ≥7.8 and \<11.1 mmol/L), with a FPG \<126 mg/dL (7.0 mmol/L).

OR

- Impaired fasting glucose (IFG), defined as an FPG ≥110 and \<126 mg/dL (≥6.1 and \<7 mmol/L), without diabetes mellitus (PPG must be \<200 mg/dL \[11.1 mmol/L\]).

OR

- Early type 2 diabetes, defined as a FPG ≥126 mg/dL (7.0 mmol/L) or a PPG of ≥200 mg/dL (11.1 mmol/L), or a previous diagnosis of diabetes, and either:

* on no pharmacological treatment (while ambulatory) for at least 10 weeks prior to screening, with screening glycated hemoglobin \<150% of the upper limit of normal (ULN) for the laboratory (eg, \<9% if the ULN is 6%)
* or taking one oral antidiabetic drug (OAD) from among sulfonylureas (SU), biguanides, thiazolidinediones (TZDs), alpha-glucosidase inhibitors (AGIs), and meglitinides (MGTs) at a stable dose while ambulatory for at least 10 weeks at the time of screening (or for the 10 weeks prior to hospitalization if identified while hospitalized for a CV event), with screening glycated hemoglobin \<133% of the ULN for the laboratory (eg, \<8% if the ULN is 6%) if taking this medication at half-maximum dose or greater, and glycated hemoglobin \<142% of the ULN for the laboratory (eg, \<8.5% if the ULN is 6%) if taking this medication at less than half-maximum dose. Individuals taking combination products containing two or more OADs were not eligible.

I2. Men or women aged 50 years and older

I3. At least one of the following CV risk factors:

* previous myocardial infarction (MI) (≥ 5 days prior to randomization)
* previous stroke (≥ 5 days prior to randomization)
* previous coronary, carotid or peripheral arterial revascularization
* angina with documented ischemic changes (at least 2 mm ST segment depression on electrocardiogram during a Graded Exercise Test \[GXT\]; or with a cardiac imaging study positive for ischemia); or unstable angina with documented ischemic changes (either ST segment depression of at least 1 mm or an increase in troponin above the normal range but below the range diagnostic for acute myocardial infarction)
* microalbuminuria or clinical albuminuria (an albumin: creatinine ratio ≥ 30 μg/mg in at least one or timed collection of urine with albumin excretion ≥20 μg/min or ≥30 mg/24 hours or total protein excretion ≥500 mg/24 hours)
* left ventricular hypertrophy by electrocardiogram or echocardiogram
* significant stenosis on angiography of coronary, carotid, or lower extremity arteries (ie, 50% or more stenosis)
* ankle-brachial index \< 0.9.

I4. Provision of signed and dated informed consent prior to any study procedures.

I5. Ability and willingness to complete study diaries and questionnaires.

I6. Demonstrated ability to use the self-glucose-monitoring device, and to self-inject insulin prior to randomization.

I7. A negative pregnancy test for all women of childbearing potential (ie, ovulating, pre- menopausal, and not surgically sterile) and the agreement of these women to use a reliable method of birth control to prevent pregnancy during the duration of the study .

I8. Willingness to discontinue prior omega-3 PUFA supplements for the duration of the study.

Exclusion criteria

E1. Type 1 diabetes.

E2. Requiring ambulatory insulin treatment or uncontrolled or symptomatic hyperglycemia that is likely to require the addition of ambulatory insulin therapy or a new antidiabetic agent either before or within 2 weeks after randomization.

E3. Known anti-glutamic acid decarboxylase antibody (anti-GAD Ab) positivity in the past.

E4. Screening glycated hemoglobin ≥150% of the ULN for the laboratory (eg, ≥9% if the ULN is 6%).

E5. Unwillingness to inject insulin or perform self-monitoring of blood glucose.

E6. Nonadherence to the run-in requirement to inject placebo insulin and do capillary glucose monitoring for at least 4 days prior to randomization.

E7. Coronary artery bypass grafting (CABG) either planned at the time of screening, or CABG within the 4 years prior to screening - however, participants with angina, MI, or stroke since a previous CABG will be eligible for randomization, even if the last CABG was within 4 years.

E8. Serum creatinine \>2.0 mg/dL (176 μmol/L) at screening.

E9. Active liver disease, or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.5 times ULN at screening.

E10. Chronic or recurrent treatment with systemic corticosteroids, or niacin treatment for hyperlipidemia.

E11. Heart failure of New York Heart Association (NYHA) Functional Class III or IV.

E12. Expected survival of \<3 years for non-CV causes such as cancer.

E13. Any other factor likely to limit protocol compliance or reporting of adverse events (AEs).

E14. Unwilling or unable to discontinue TZDs.

E15. Simultaneous participation in any other clinical trial of an active pharmacologic agent.

E16. Unwillingness to permit sites to contact their primary physicians to communicate information about the study and the participant's data and treatment assignment.

E17. History of hypersensitivity to the investigational products.

E18. Previous randomization in this study.

E19. A prior heart transplant, or awaiting a heart transplant.

E20. Known infection with human immunodeficiency virus (HIV).
B: 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.
C: Inclusion Criteria:

* The participant (and/or their parent/legal guardian) was willing and able to provide signed informed consent prior to any study-related procedures to be performed;
* The participant was at least 16 years old at the time of randomization;
* The participant had a confirmed diagnosis of Gaucher disease Type 1;
* Female participants of childbearing potential must had a documented negative pregnancy test prior to dosing. In addition all female participants of childbearing potential must use a medically accepted form of contraception throughout the study.

Exclusion Criteria:

* The participant has had a partial or total splenectomy;
* The participant had received pharmacological chaperones or miglustat within 6 months prior to randomization;
* The participant had received enzyme replacement therapy within 9 months prior to randomization;
* The participant had Type 2 or 3 Gaucher disease or was suspected of having Type 3 Gaucher disease;
* The participant had any clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal (GI), pulmonary, neurologic, endocrine, metabolic, (for example, hypokalemia, hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illness that might confound the study results, or, on the opinion of the investigator, might preclude participation in the study;
* The participant had tested positive for the human immunodeficiency virus (HIV) antibody, Hepatitis C antibody, or Hepatitis B surface antigen;
* The participant had received an investigational product within 30 days prior to randomization;
* The participant was pregnant or lactating.
D: Inclusion Criteria:

* The participant had a diagnosis of Gaucher Type I disease and a documented deficiency of glucocerebrosidase activity by enzyme assay and was willing and able to provide written informed consent prior to initiating any study-related procedures;
* The participant was 18 to 65 years old and weighed between 50 and 120 kilogram (kg) at enrollment;
* The participant had the following symptoms of Gaucher disease identified within 28 days of enrollment (at screening);

  * Anemia - indicated by hemoglobin measurements taken during the screening phase (8 to 10 gram per deciliter (g/dL) if female, 8 to 11 g/dL if male);
  * Thrombocytopenia - indicated by platelet count measurements taken during the screening phase (60000 to 100000 per cubic millimeter);
  * Splenomegaly, as indicated by magnetic resonance imaging (MRI) or spiral computed tomography (CT) (\>= 10 multiples of normal);
* Female participants of child-bearing potential must had a documented negative serum pregnancy test prior to dosing. Female participants agreed to use a reliable method of birth control throughout duration of trial.

Exclusion Criteria:

* Participant had a partial or total splenectomy or infarcted areas of the spleen;
* Participant had documented prior bleeding varices or liver infarction;
* Participant received miglustat within 12 months prior to study enrollment;
* The participant had received an investigational product within 30 days prior to study enrollment;
* Participant had neurologic or pulmonary involvement;
* Participant had new pathological bone involvement or bone crisis in the 12 months prior to enrollment;
* Participant was transfusion-dependent;
* Participant had a documented etiology of anemia due to causes other than Gaucher disease;
* The participant had cardiac functional and/or anatomical abnormalities, a history of cancer or tested positive for human immunodeficiency virus (HIV) antibody or Hepatitis;
* Participant had a clinically significant disease, other than Gaucher disease, including cardiovascular, renal, hepatic, gastrointestinal, pulmonary, neurologic, endocrine, metabolic, or psychiatric disease, other medical conditions, or serious intercurrent illnesses that, in the opinion of the Investigator, might preclude participation in the study.

Answer: B