Phase III Study of ISU302 in Patients With Type 1 Gaucher Disease

A Multicenter, Open-Label Phase III Study to Evaluate the Safety and Efficacy of ISU302 (Imiglucerase for Injection) in Patients With Type 1 Gaucher Disease

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02770625

Enrollment

Registered

2016-05-12

Start date

2011-09-30

Completion date

2014-08-31

Last updated

2017-07-12

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Gaucher Disease, Type 1

Keywords

Type I Gaucher, ISU302, Imiglucerase

Brief summary

The purpose of this study is to evaluate the safety and efficacy of ISU302 in patients with Type 1 Gaucher disease.

Detailed description

The objectives of this clinical study were to evaluate the efficacy and safety of every other week (EOW) dosing of ISU302 at a dose of 60 U/kg as an effective glucocerebrosidase enzyme replacement therapeutic product in patients with Type 1 Gaucher disease (GD). Primary efficacy endpoint was the difference in hemoglobin concentration between baseline and Week 24. Secondary efficacy endpoints included assessment of platelet counts, spleen and liver volume, and biomarker levels in plasma at Week 24 compared to baseline; skeletal change and bone mineral density (BMD); and single-dose pharmacokinetic (PK) analysis. Secondary safety endpoints included the assessment of adverse events (AEs), vital signs, physical examination, and electrocardiogram (ECG); clinical safety laboratory analyses included serum chemistry, urinalysis, hematology and coagulation, and the measurement of anti-ISU302 antibodies.

Interventions

DRUGISU302

60 U/kg given intravenously

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

2 Years to No maximum

Healthy volunteers

Inclusion criteria

* Diagnosis of Type 1 GD. * Documented glucocerebrosidase deficiency. * GD-related anemia, defined as hemoglobin levels of at least 1 g/dL below the lower limit of normal for age and gender and one or more of the following 3 criteria: * At least moderate splenomegaly (2 to 3 cm below the left costal margin) by palpation, * GD-related thrombocytopenia, defined as a platelet count \<90 x 109 platelets/L, * GD-related readily palpable enlarged liver. * Not received treatment for GD (investigational products, miglustat, velaglucerase alfa, or imiglucerase) within 12 months prior to study entry. * Ability to comprehend and willing to sign the ICF. * Legal guardian (and patient if age appropriate) understood the nature of the procedure, was willing to comply with associated follow-up evaluations, and provided written informed consent and assent prior to the procedure. * Female patients of childbearing potential must had agreed to use a medically acceptable method of contraception at all the times during the study. Male patients must have used a medically acceptable method of birth control throughout their participation in the study and were required to report the pregnancy of a partner.

Exclusion criteria

* Type 2 or 3 GD. * Splenectomy. * Antibody positive to ISU302 or imiglucerase during screening or the patient had experienced an anaphylactic reaction to ISU302 or imiglucerase. - Treatment with any non-GD-related investigational drug or medical device within 30 days prior to study entry; such use during the study was also not permitted. * Currently receiving red blood cell (RBC) growth factor (eg, erythropoietin) chronic systemic corticosteroids or received such treatment within the last 6 months. * Positive for human immunodeficiency virus (HIV) and hepatitis B or C. * Exacerbated anemia at screening (due to iron, folic acid, or vitamin B12 deficiency or infectious/immune-mediated cause). * Significant comorbidity(ies) that could affect study data or confounded the study results (eg, malignancies, primary biliary cirrhosis, autoimmune liver disease). * Pregnant or lactating female patients and those not willing to use highly effective barrier or medical method of contraception.

Design outcomes

Primary

Measure	Time frame
The Difference in Hemoglobin Concentration [g/dL]	from baseline to Week 24

Secondary

Measure	Time frame	Description
Platelet Counts [10^3 Platelets/uL]	from baseline to Week 24	—
Spleen Volume	from baseline to Week 24	—
Liver Volume	from baseline to Week 24	—
Angiotensin-converting Enzyme Level	from baseline to Week 24	—
Chemokine Ligand (CCL-18) Level [ng/mL]	from baseline to Week 24	—
Acid Phosphatase (ACP) Level (U/L)	from baseline to Week 24	—
Skeletal Status Improvement	from baseline to Week 24	The number of participant who have the skeletal status diagnosed as Osteosclerosis
Change in Bone Mineral Density	from baseline to Week 24	—
Chitotriosidase Level (Nmol/mL/hr)	from baseline to Week 24	—

Other

Measure	Time frame
Assessment of AEs, Vital Signs, Physical Examination, and Electrocardiogram (ECG)	Screening to Visit14 (Week 26)

Participant flow

Pre-assignment details

A total of 9 patients were planned to be enrolled in the study; 8 patients were enrolled into the study and all 8 patients completed the study.

Participants by arm

Arm	Count
ISU302 60 U/kg (once every 2 weeks for 6 months) ISU302: 60 U/kg given intravenously	8
Total	8

Baseline characteristics

Characteristic	ISU302
Age, Continuous	5.8 years STANDARD_DEVIATION 4.74
Body Mass Index (BMI)	17.244 Kilogram per square meter (kg/m^2) STANDARD_DEVIATION 1.9236
Height	100.40 cm STANDARD_DEVIATION 22.852
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	0 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	8 Participants
Weight	17.9 kg STANDARD_DEVIATION 7.64

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 8
other Total, other adverse events	0 / 8
serious Total, serious adverse events	3 / 8