A multicenter open-label study of Gene-Activated Human Glucocerebrosidase (GA-GCB) enzyme replacement therapy in patients with type 1 Gaucher disease previously treated wiht imiglucerase. - TKT034

Phase 1

• Conditions: Type I Gaucher Disease; MedDRA version: 9.1Level: LLTClassification code 10018048Term: Gaucher's disease

• Registration Number: EUCTR2006-006304-11-DE
• Lead Sponsor: Shire Human Genetic Therapies Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-11-02
• Last Update Posted: 2 October 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

The patient has a documented diagnosis of type 1 Gaucher disease, as documented by deficient glucocerebrosidase (GCB) activity in leukocytes or by genotype analysis.

The patient has received consistent treatment with imiglucerase for a minimum of 30 consecutive months. Consistent treatment is defined as a prescribed dosing interval of every other week at a dose = 60 U/kg and = 15 U/kg. Patients must have received the same dose during the 6 months prior to study enrollment. Minor dosing interval variance is allowed as reflected in standard clinical practice.

The patient is at least 2 years of age.

Female patients of child bearing potential must agree to use a medically acceptable
method of contraception at all times during the study and must have negative results
to a pregnancy test performed at Screening and as required throughout their
participation in the study. Male patients must use a medically acceptable method of birth control throughout their participation in the study and must report their partner’s pregnancy.

The patient, the patient’s parent(s) or legal guardian(s) has provided written informed consent that has been approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC).

The patient must be sufficiently cooperative to participate in this clinical study as
judged by the Investigator.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients who meet any of the following criteria are not eligible for this study:
1. The patient has both a hemoglobin concentration = 10 g/dL and a platelet count = 80 x 10,000 platelets/cubic mm3.
2. The patient has unstable hemoglobin concentration during the six months prior to Screening. Stable hemoglobin concentration is defined as the average of all values in the past six months falling within a range of + 1 g/dL of the Screening value. If at least three consecutive values, including Screening, in the previous 6 months are not available, the three most recent values will be considered. At least one of the values must be six months prior to Screening. In addition, the difference between the highest and lowest values cannot exceed 1.5 g/dL. Values within the first 12 months of treatment initiation with ERT will be excluded.
3. The patient has unstable platelet count during the six months prior to Screening. Stable platelet count is defined as the average of all values in the past six months falling within a range of + 20 % of the Screening value. If at least three consecutive values, including Screening, in the previous 6 months are not available, the three most recent values will be considered. At least one of the values must be six months prior to Screening. In addition, the difference between the highest and lowest values cannot exceed 20% of the highest value. Values within the first 12 months of treatment initiation with ERT will be excluded.
4. The patient has type 2 or 3 Gaucher disease or is suspected of having type 3 Gaucher disease.
5. The patient has received treatment with any investigational drug or device within the 30 days prior to study entry; such use during the study is not permitted.
6. The patient is known to be positive for human immunodeficiency virus (HIV), i.e., has a documented positive result. Patients who do not have a documented positive result will be tested for HIV during Screening.
7. The patient is known to be positive for hepatitis B or hepatitis C, i.e., has a documented positive result. Patients who do not have a documented positive result will be tested for hepatitis during Screening.
8 The patient presents with sustained iron, folic acid or vitamin B12 deficiency-related anemia during Screening (i.e., non-Gaucher disease-related anemia).
9 The patient, patient’s parent(s), or patient’s legal guardian(s) is/are unable to understand the nature, scope, and possible consequences of the study.
10 The patient has a significant comorbidity that might affect study data or confound the study results (e.g., malignancies, primary biliary cirrhosis, autoimmune liver disease, etc.).
11 The patient is unable to comply with the protocol, e.g., has a clinically relevant medical condition making implementation of the protocol difficult, has an uncooperative attitude, is unable to return for safety evaluations, or is otherwise unlikely to complete the study, as determined by the Investigator.
12. The patient has had inconsistent treatment with imiglucerase in the last 6 months.
13. The patient has experienced an anaphylactic or anaphylactoid reaction during treatment with imiglucerase.
14. The patient has received miglustat during the 6 months prior to study enrollment.
15. The patient is currently receiving red blood cell growth factor, (e.g., erythropoietin) or chronic systemic corticosteroids in the last 6 months. (NOTE: Inhaled corticosteroid therapy, e.g., treatment for ast

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety of every other week dosing of GA-GCB in patients with type 1 Gaucher disease who were previously treated with imiglucerase.;Secondary Objective: To evaluate changes from Baseline in hemoglobin concentration after every other<br>week dosing of GA-GCB.<br><br>To evaluate changes from Baseline in platelet count after every other week dosing of GA-GCB.<br><br>To evaluate changes from Baseline in liver and spleen volumes by (MRI) after every other week dosing of GA-GCB.;Primary end point(s): to evaluate the safety of every other week dosing of GA-GCB in patients with type 1 Gaucher disease who were previously treated with imiglucerase. Safety assessments include adverse events (including infusion-related adverse events), concomitant medication use, vital signs, 12-lead ECG, physical examinations, and clinical laboratory tests (hematology, serum chemistry, urinalysis, and anti-GA-GCB antibody testing).