An Open-label, Multicenter, Single-arm, Phase 4 Study of the Effect of Treatment With Velaglucerase Alfa on Bone-related Pathology in Treatment-naïve Patients With Type 1 Gaucher Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 21
- 试验地点
- 15
- 主要终点
- Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-Score up to End of Study (EOS) (Week 103)
研究概览
简要总结
The primary purpose of this study is to evaluate the effect of VPRIV therapy (60 units per kilogram [U/kg] every other week [EOW]) in treatment-naive participants 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant 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 participant's medical history.
- •Participants must have a LS BMD Z-score less than (<) -1 or BMD T-score of < -1 as measured by DXA during the screening phase.
- •Participant is treatment-naive, that is (ie,) has not received ERT or SRT in the 12 months prior to enrollment.
- •The participant is greater than or equal to (>=) 18 and less than or equal to (<=) 70 years of age.
- •Female participants of childbearing potential must agree to use a medically acceptable method of contraception at all times during the study.
- •The participant, or participant'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).
- •The participant must be sufficiently cooperative to participate in this clinical study as judged by the investigator.
- •Exclusion criteria
- •Neurological symptoms indicating that the participant may have type 3 Gaucher disease.
- •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).
- •Any osteoporosis-specific treatment (eg, bisphosphonates) or treatment with erythropoietin (or erythropoietin-like substances) during the past year.
- •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 (example, pain).
- •The participant is pregnant or lactating.
- •The participant has had a splenectomy. (This criterion is not meant to exclude participants who have accessory spleens.)
- •The participant 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.
- •Severe vitamin D deficiency to the level that would be expected to result in osteomalacia (vitamin D < 10 nanograms per milliliter [ng/mL] [25 nanomoles per liter {nmol/L}]). If there is mild vitamin D insufficiency at screening (vitamin D greater than [>] 10 and < 30 ng/mL) treat with 4000 IU vitamin D per day for 1 month and rescreen.
- •The participant has previously interrupted ERT for safety reasons.
- •The participant has had hypersensitivity to the active substance or to any of the excipients.
排除标准
- 未提供
研究组 & 干预措施
Velaglucerase alfa 60 U/kg
Participants will receive 60-minute intravenous infusion of 60 units per kilogram (U/kg) velaglucerase alfa every other week (EOW) and an oral daily dose of 800 IU vitamin D for 24 months (101 weeks).
干预措施: Velaglucerase alfa (Drug)
Velaglucerase alfa 60 U/kg
Participants will receive 60-minute intravenous infusion of 60 units per kilogram (U/kg) velaglucerase alfa every other week (EOW) and an oral daily dose of 800 IU vitamin D for 24 months (101 weeks).
干预措施: Vitamin D (Dietary Supplement)
结局指标
主要结局
Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-Score up to End of Study (EOS) (Week 103)
时间窗: Baseline up to EOS (Week 103)
Bone mineral density of the lumbar spine was measured by dual energy x-ray absorptiometry (DXA), and the results was converted to Z-scores appropriate for age, sex, and race. The Z-score indicated the number of standard deviations away from a reference population in the same age range, race and with the same sex. A Z-score of 0 was equal to the mean. Negative numbers indicated values lower than the mean and positive numbers indicated values higher than the mean. Baseline was defined as last data collected prior to the first administration of study drug. Change from baseline in lumbar spine BMD Z-Score up to EOS (Week 103) was reported.
次要结局
- Change From Baseline in Lumbar Spine (LS) BMD Z-score at Week 51(Baseline, Week 51)
- Change From Baseline in Lumbar Spine BMD at Week 51 and EOS (Week 103)(Baseline, Week 51 and EOS (Week 103))
- Change From Baseline in Total Bone Marrow Burden (BMB) Score at Week 51 and EOS (Week 103)(Baseline, Week 51 and EOS (Week 103))
- Change From Baseline in Normalized Liver Volume at Week 51 and EOS (Week 103)(Baseline, Week 51 and EOS (Week 103))
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(From start of study drug infusion up to follow-up (107 weeks))
- Number of Participants Who Developed Positive Anti-velaglucerase Alfa Antibody Status(Baseline up to EOS (Week 103))
- Change From Baseline in Hemoglobin Concentration at Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)(Baseline, Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103))
- Change From Baseline in Platelet Count at Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)(Baseline, Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103))
- Number of Participants With Shift in World Health Organization (WHO) BMD Classifications Based on LS T-Scores at Week 51 and EOS (Week 103)(Baseline, Week 51 and EOS (Week 103))
- Change From Baseline in Normalized Spleen Volume at Week 51 and EOS (Week 103)(Baseline, Week 51 and EOS (Week 103))
- Change From Baseline in Severity of Bone Pain at Week 51 and EOS (Week 103)(Baseline, Week 51 and EOS (Week 103))
- Change From Baseline in Overall Fatigue Measured by Brief Fatigue Inventory (BFI) at Week 51 and EOS (Week 103)(Baseline, Week 51 and EOS (Week 103))
- Change From Baseline in Bone Pain Interference Score at Week 51 and EOS (Week 103)(Baseline, Week 51 and EOS (Week 103))