Clinical trial NCT02574286: Study of the Effect of Velaglucerase Alfa (VPRIV®) on Bone-related Pathology in Treatment-naïve Participants With Type 1 Gaucher Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Gaucher Disease
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-10-12
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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.

Primary outcomes:
measure: Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) Z-Score up to End of Study (EOS) (Week 103)
timeFrame: Baseline up to EOS (Week 103)
Secondary outcomes:
measure: Change From Baseline in Lumbar Spine (LS) BMD Z-score at Week 51
timeFrame: Baseline, Week 51
measure: Change From Baseline in Lumbar Spine BMD at Week 51 and EOS (Week 103)
timeFrame: Baseline, Week 51 and EOS (Week 103)
measure: Change From Baseline in Total Bone Marrow Burden (BMB) Score at Week 51 and EOS (Week 103)
timeFrame: Baseline, Week 51 and EOS (Week 103)
measure: Change From Baseline in Hemoglobin Concentration at Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)
timeFrame: Baseline, Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)
measure: Change From Baseline in Platelet Count at Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)
timeFrame: Baseline, Week 13, 25, 37, 51, 65, 77, 89, and EOS (Week 103)
measure: Change From Baseline in Normalized Liver Volume at Week 51 and EOS (Week 103)
timeFrame: Baseline, Week 51 and EOS (Week 103)
measure: Change From Baseline in Normalized Spleen Volume at Week 51 and EOS (Week 103)
timeFrame: Baseline, Week 51 and EOS (Week 103)
measure: Change From Baseline in Severity of Bone Pain at Week 51 and EOS (Week 103)
timeFrame: Baseline, Week 51 and EOS (Week 103)
measure: Change From Baseline in Bone Pain Interference Score at Week 51 and EOS (Week 103)
timeFrame: Baseline, Week 51 and EOS (Week 103)
measure: Change From Baseline in Overall Fatigue Measured by Brief Fatigue Inventory (BFI) at Week 51 and EOS (Week 103)
timeFrame: Baseline, Week 51 and EOS (Week 103)
measure: Number of Participants With Shift in World Health Organization (WHO) BMD Classifications Based on LS T-Scores at Week 51 and EOS (Week 103)
timeFrame: Baseline, Week 51 and EOS (Week 103)
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: From start of study drug infusion up to follow-up (107 weeks)
measure: Number of Participants Who Developed Positive Anti-velaglucerase Alfa Antibody Status
timeFrame: Baseline up to EOS (Week 103)
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente
state: California
city: Atlanta
country: United States
facility: Emory Genetics
state: Georgia
city: Chicago
country: United States
facility: Ann and Robert H Lurie Childrens Hospital of Chicago
state: Illinois
city: New York
country: United States
facility: NYU School of Medicine
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Fairfax
country: United States
facility: Lysosomal and Rare Disorders Research and Treatment Center
state: Virginia
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Jerusalem
country: Israel
facility: Shaare Zedek Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Zaragoza
country: Spain
facility: Hospital Quironsalud Zaragoza
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
Study officials:
affiliation: Shire
name: Study Director
role: STUDY_DIRECTOR
References: