An Open-Label, Phase IV Study of Velaglucerase alfa on Bone Related Pathology in Adult, Treatment-Naïve Patients with Type 1 Gaucher Disease

Phase 1

• Conditions: Gaucher Disease; MedDRA version: 20.0Level: PTClassification code 10075697Term: Gaucher's disease type ISystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

• Registration Number: EUCTR2015-001578-17-DE
• Lead Sponsor: Shire Human Genetic Therapies, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-12-22
• Last Update Posted: 7 January 2019

Recruitment & Eligibility

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

Inclusion Criteria

Each patient must meet the following criteria to be enrolled in this study.
1. The patient has a documented diagnosis of type 1 Gaucher disease, as documented by deficient GCB activity in leukocytes (whole blood only) or cultured skin fibroblasts.
Diagnosis by only dry blood spot test is insufficient. Diagnosis may be based on results obtained prior to screening if documented in the patient’s medical history.
2. Patients must have a LS BMD Z-score < -1 or BMD T-score of < -1 measured by DXA during the screening phase.
3. Patient is treatment-naïve, ie, has not received ERT or SRT in the 12 months prior to enrollment.
4. The patient is =18 and =70 years of age.
5. Female patients of childbearing potential must agree to use a medically acceptable method of contraception at all times during the study. (See Section 6.8.3 for acceptable methods of contraception).
6. The patient, or patient’s legally authorized representative(s), if applicable, understands the nature, scope, and possible consequences of the study and has provided written informed consent that has been approved by the Institutional Review Board/Independent Ethics Committee (IRB/IEC).
7. The patient must be sufficiently cooperative to participate in this clinical study as judged by the investigator.
Are the trial subjects under 18? no
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 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 10

Exclusion Criteria

Patients who meet any of the following criteria will be excluded from the
study.
1. Neurological symptoms indicating that the patient may have type 3
Gaucher disease.
2. A significant comorbidity, which, as determined by the investigator,
might affect study data or confound the study results (eg, malignancies,
primary biliary cirrhosis, autoimmune liver disease, etc).
3. Any osteoporosis-specific treatment (eg, bisphosphonates) or
treatment with erythropoietin (or erythropoietin-like substances) during
the past year.
4. Structural, joint-associated bone damage of such extent and severity
that the investigator deems it could impact participation in the study and
assessment of relevant study endpoints (eg, pain).
5. The patient is pregnant or lactating.
6. The patient has had a splenectomy.
7. The patient is enrolled in another clinical study that involves clinical
investigations or use of any investigational product (drug or device)
within 30 days prior to study enrollment or at any time during the study.
8. Severe vitamin D deficiency to the level that would be expected to
result in osteomalacia (vitamin D < 10 ng/mL [25 nmol/L]). If there is
mild vitamin D insufficiency at screening (vitamin D > 10 and < 30
ng/mL) treat with 4000 IU vitamin D per day for 1 month and rescreen.
9. The patient has previously interrupted ERT for safety reasons.
10. The patient has had hypersensitivity to the active substance or to
any of the excipients.

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 effect of VPRIV therapy (60 U/kg EOW) in treatment-naïve patients with type 1 Gaucher disease on change from baseline in lumbar spine (LS) bone mineral density (BMD) Z-score as measured by dual energy x-ray absorptiometry (DXA) after 24 months of treatment;Secondary Objective: To evaluate the effect of VPRIV therapy (60 U/kg EOW) on bone mineral density (BMD) in treatment-naïve patients with type 1 Gaucher disease as measured by the change from baseline in LS BMD Z-score at 12 months, and bone marrow burden (BMB) as measured by magnetic resonance imaging (MRI) of the LS and femur after 12 and 24 months of treatment<br>;Primary end point(s): Change from baseline to 24 months (Week 103 [end of study]) in LS BMD Z-score as measured by DXA. ;Timepoint(s) of evaluation of this end point: Assessments will be performed at the screening visit and Weeks 51 and 103 (end of study).

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The key secondary endpoints of this study are:<br>• Change from baseline to 12 months (Week 51) and 24 months (Week<br>103 [end of study]) in BMB score (MRI of LS and femur). Assessments<br>will be performed at the baseline visit and Weeks 51 and 103 (end of<br>study).<br>• Change from baseline to 12 months (Week 51) in LS BMD Z-score.<br>Assessments will be performed at the screening visit and Weeks 51 and<br>103 (end of study). ;Timepoint(s) of evaluation of this end point: Assessments will be performed at the baseline visit and Weeks 51 and 103 (end of study).<br><br>Assessments will be performed at the screening visit and Weeks 51 and<br>103 (end of study).