VPRIV Clinical Studies
Clinical Study Overview
We have mentioned how VPRIV was studied in the largest clinical trial program for an ERT in type 1 Gaucher disease—but what exactly does that mean when considering VPRIV? Clinical studies investigate how treatments affect different health-related outcomes in patients in a controlled environment. The safety and efficacy of VPRIV were evaluated in 99 adults and children aged 4 years and older who had been diagnosed with GD1, in various stages of life, across three initial clinical trials. Some of these patients then went on to take part in a 5-year long-term extended study.
The following sections will take a deeper look into the individual studies that made up this clinical trial program to help explain their relevance for patients considering VPRIV as part of their treatment journey. The studies have been divided into two sections:
- New to treatment (treatment-naïve): studies involving patients who were not receiving treatment for type 1 Gaucher disease prior to enrollment in the clinical trial
- New to VPRIV (treatment-experienced): studies involving patients who were receiving imiglucerase treatment for at least 2.5 years before starting treatment with VPRIV as part of the clinical trial
Clinical Studies: New to Treatment
If you are unfamiliar with any of the terms used throughout this section, please consult our Glossary for useful definitions.
12-Month Parallel-Dose Study
In the 12-month parallel-dose study, 25 participants who were new to treatment (treatment-naïve), aged 4 years and older, with type 1 Gaucher disease were randomly assigned to receive two different doses of VPRIV for 12 months. The trial was double-blind, meaning that neither the patients nor the study investigators knew which dose had been assigned to which participant. A double-blind study therefore allows the investigators to interpret the results objectively.
study 1 : 12-MONTH STUDY RESEARCH OBJECTIVES
study 1 : 12-MONTH STUDY RESEARCH OBJECTIVES
25 adults and children aged 4 years and older
VPRIV 45 units/kg once every other week (13 patients)
VPRIV 60 units/kg once every other week (12 patients)
Primary: Change in red blood cell concentration from baseline to 12 months in the 60 Units/kg treatment group.
SECONDARY: Change in red blood cell count from the start to the end of the study in the 45 Units/kg treatment group; changes in platelet (blood-clotting cell) count, and spleen and liver volumes for both treatment groups.
Additional study details:
- Patients were randomly assigned to two groups that received one of two doses: 45 Units/kg or 60 Units/kg*
- Patients were 4–62 years of age
- Both doses were given as 60-minute infusions, administered at the study center once every other week
- Participants were eligible only if considered new to treatment, which was defined as not having received treatment for type 1 Gaucher disease in the 30 months prior to study entry
- The study lasted for 52 weeks, which meant there were a total of 26 infusions analyzed
Key findings:
After 12 months, VPRIV was seen to deliver improvements in hemoglobin levels from baseline (measurements taken at the beginning of the study) in the 60 Units/kg group, which was the primary objective for this study. Differences from baseline levels in the 45 Units/kg treatment group were observed from secondary objectives.
- Between the start and end of the study, the researchers found meaningful changes in hemoglobin levels; levels of this oxygen-carrying protein in red blood cells were seen to increase in both treatment groups. This means that the primary objective of the study, which was hemoglobin change in the 60 Units/kg group, was met
- Platelet counts in both groups also showed a meaningful change, meaning participants had higher amounts of the cell fragments that form clots and help to stop or prevent bleeding by the end of this study
- Spleen and liver volumes in both treatment groups had decreased, although the decrease in liver volume was not statistically significant in this study
- No infusion-related serious adverse events were reported for the duration of the parallel-dose study trial, and no participants needed to stop treatment before the trial ended. However, in the full scope of the VPRIV clinical trials, some patients experienced hypersensitivity, or a serious allergic reaction. Talk to your doctor and visit our Safety and Tolerability information to learn more
- All patients who participated in the parallel-dose study trial were eligible to partake in the 5-Year Long-Term Extension Study
*Please note that the 45 Units/kg dose is not the recommended starting dose in patients new to treatment. The recommended starting VPRIV dosage in naïve adults and naïve pediatric patients 4 years of age and older is 60 Units/kg administered every other week as a 60-minute intravenous infusion. Learn more about how VPRIV is dosed and administered here.
AVERAGE CHANGE (%) FROM STUDY START
12 months VPRIV 60 Units/kg every other week
Increasing red blood cell and platelet counts
Decreasing spleen and liver volumes
23%
n=12
66%
n=12
-50%
n=12
-17%
n=12
*This decrease was not
statistically
significant
after adjusting for
multiple tests.
100
50
0
0
-50
-100
*This decrease was not statistically significant after adjusting for multiple tests.
n = Number of patients
Primary research objective
Red blood cell count
Average hemoglobin concentration at baseline: 10.6 g/dL
Average change at 12 months: 2.4 g/dL ± 0.3 (SE)
Primary research objective
Secondary research objectives
Platelet count
Average platelet count at baseline: 97 x 109/L
Average change at 12 months: 51 x 109/L ± 12 (SE)
Spleen volume
Average spleen volume at baseline: 2.9% of body weight
Average change at 12 months: -1.9% ± 0.5 of body weight
Liver volume
Average liver volume at baseline: 3.6% of body weight
Average change at 12 months: -0.84% ± 0.33 of body weight
Secondary research objectives
9-Month Comparison Study (Non-inferiority study)
In the 9-month comparison "Non-Inferiority" study, 34 adults and children aged 4 years and older with type 1 Gaucher disease were randomly assigned to receive imiglucerase or VPRIV for 9 months. Patients were assigned treatments without themselves or the researchers knowing which treatment they received, which helped the researchers and participants to avoid introducing bias into the results documented.
study 2: 9-MONTH COMPARISON STUDY RESEARCH OBJECTIVES
study 2: 9-MONTH COMPARISON STUDY RESEARCH OBJECTIVES
34 adults and children aged 4 years and older
VPRIV 60 units/kg once every other week (17 patients)
Imiglucerase 60 units/kg once every other week (17 patients)
Primary: Difference in the average change from the start to the end of the study in red blood cell count between the two groups.
SECONDARY: Differences in changes from the start to the end of the study in average platelet count, and spleen and liver volumes between the two groups.
Additional study details:
- 26% of the patients in the study (9 patients) were children, aged 4 years and older
Key findings:
VPRIV successfully demonstrated noninferiority to imiglucerase.
- Hemoglobin levels in both groups increased to a similar level, which supported the aim of this study to show that VPRIV is noninferior to imiglucerase
- Changes in platelet counts, as well as spleen and liver volumes, were also similar between the two groups, further supporting the noninferiority of VPRIV
- No patients in the VPRIV treatment group developed anti-drug antibodies in response to VPRIV in this study, whereas 4 patients in the imiglucerase treatment group developed antibodies to imiglucerase. It is thought that antibodies could indicate an adverse response to treatment, although further research is needed to confirm this. Learn more about developing antibodies to VPRIV here
- Throughout clinical trials of VPRIV, some patients experienced hypersensitivity, or a serious allergic reaction. It is important to make yourself aware of the reactions experienced by some VPRIV users, which can be found here
AVERAGE CHANGE (%) FROM STUDY START
Increasing red blood cell and platelet counts
Decreasing spleen and liver volumes
14%
n=17
77%
n=17
-50%
n=7
-25%
n=17
100
50
0
0
-50
-100
PATIENTS RECIEVING 60 UNITS/KG IMIGLUCERASE ONCE EVERY OTHER WEEK FOR 9 MONTHS
PATIENTS RECIEVING 60 UNITS/KG VPRIV ONCE EVERY OTHER WEEK FOR 9 MONTHS
n = Number of patients
*Baseline values are for both treatment groups
Primary research objective
Red blood cell count
Average red blood cell concentration at baseline*: VPRIV, 11.0 g/dL; imiglucerase, 10.6 g/dL
Average treatment difference (VPRIV to imiglucerase) at 9 months: 0.1 g/dL ± 0.4 (SE)
Primary research objective
Secondary research objectives
Platelet count
Average platelet count at baseline*: VPRIV, 171 x 109/L; imiglucerase, 188 x 109/L
Average treatment difference (VPRIV to imiglucerase) at 9 months: -39 x 109/L
Spleen volume
Average spleen volume at baseline*: VPRIV, 3.4% of body weight; imiglucerase, 1.4% of body weight
Average treatment difference (VPRIV to imiglucerase) at 9 months: 0.1% of body weight
Liver volume
Average liver volume at baseline*: VPRIV, 4.3% of body weight; imiglucerase, 4.0% of body weight
Average treatment difference (VPRIV to imiglucerase) at 9 months: 0.1% of body weight
Secondary research objectives
5-Year Long-Term Extension Study
All 25 patients who completed the 12-month parallel-dose study and 32 out of 34 patients from the 9-month comparison study then opted to enroll in the 5-year long-term extension study. All patients were administered 60 Units/kg VPRIV as a 60-minute infusion once every other week. The study was open-label, which means that all patients and researchers involved knew all participants in the study were receiving VPRIV.
STUDY 4: 5-YEAR LONG-TERM STUDY RESEARCH OBJECTIVES
Studies 1 & 2 Overall VPRIV (41 patients)
Study 2 Imiglucerase to VPRIV
(16 patients)
VPRIV 60 units/kg once every other week
(57 patients)*
Primary: To evaluate the long-term safety of VPRlV treatment.
SECONDARY: To evaluate the effects of treatment on red blood cell and platelet counts, and liver and spleen volumes.
*One patient from each group in Study 2 did not participate in Study 4
In the initial studies (Study 1 and Study 2), all patients were new to treatment; patients in Study 2 received different treatments (VPRIV and imiglucerase). The following results are specific to the patient subsets that only received VPRIV in these initial trials.
At 24 months, patients demonstrated improvements from the start of Study 1 and Study 2 in clinical measures. Improvements were maintained for up to 5 years.
AVERAGE INCREASE IN RED BLOOD CELL COUNT
At 12 months, baseline: 10.6 g/dL; average change from the start of Studies 1 and 2: 2.4 g/dL
At 24 months, baseline: 11.0 g/dL; average change from the start of Studies 1 and 2: 2.8 g/dL
AVERAGE INCREASE IN PLATELET COUNT
At 12 months, baseline: 97 × 109/L; average change from the start of Studies 1 and 2: 51 x 109/L
At 24 months, baseline: 108.6 × 109/L; average change from the start of Studies 1 and 2: 87.9 x 109/L
AVERAGE DECREASE IN SPLEEN VOLUME
At 12 months, baseline: 2.9% of body weight; average change from the start of Studies 1 and 2: -1.9% of body weight
At 24 months, baseline: 3.8% of body weight; average change from the start of Studies 1 and 2: -2.7% of body weight
AVERAGE DECREASE IN LIVER VOLUME
At 12 months, baseline: 3.6% of body weight; average change from the start of Studies 1 and 2: -0.84% of body weight
At 24 months, baseline: 4.0% of body weight; average change from the start of Studies 1 and 2: -1.2% of body weight
n = Number of patients
BL = Baseline (Baseline was defined as being before the first dose in the initial study)
Pediatric Patients
The safety and efficacy of VPRIV have been established for children aged 4–17 years with type 1 Gaucher disease and were found to be similar in children and adults.
The recommended starting dose for children aged 4 years and older is 60 Units/kg once every other week as a 60-minute infusion. VPRIV should be administered under the supervision of a healthcare professional.
In a subgroup of 24 children who participated in the 5-year long-term extension study, safety results were consistent with those of the other participants:
- No new safety concerns were identified
- No serious side effects were related to treatment with VPRIV
- No serious infusion-related side effects occurred
- No patient stopped participating in the study due to a side effect
- One pediatric patient tested positive for antibodies to VPRIV in the 5-year long-term extension study. Learn more about developing antibodies to VPRIV here
- Side effects more common in children than in adults (>10% difference) include: rash, increased time for blood to clot, and fever
- The safety and efficacy of VPRIV have not been established in children younger than 4 years of age. Learn more about the safety profile of VPRIV here
Clinical Studies: New to VPRIV
If you are unfamiliar with any of the terms used throughout this section, please consult our Glossary for useful definitions.
12-Month Switch Study
In the 12-month switch study, 40 patients aged 9 years and older, who had previously received treatment with imiglucerase, were treated with VPRIV at the same dose once every other week for 12 months. The study was open-label, which means that all patients and researchers involved knew which treatment all participants were receiving.
STUDY 3: 12-MONTH SWITCH STUDY RESEARCH OBJECTIVES
STUDY 3: 12-MONTH SWITCH STUDY RESEARCH OBJECTIVES
Patients treated with imiglucerase for ≥2.5 years
VPRIV
15–60 units/kg once
every other week (40 patients)
Primary: To evaluate the safety of once every other week dosing of VPRIV in switch patients.
SECONDARY: Change from the start to the end of the study in red blood cell count, and percentage change from the start to the end of the study in platelet count and spleen and liver volumes normalized by body weight.
Additional study details:
- The age of participants ranged from 9 to 71 years old
- To be eligible for the study, all participants had to be diagnosed with GD1 and had to have been receiving imiglucerase treatment for 30 consecutive months prior to starting the trial
Key findings:
Over 12 months, stability versus baseline levels were maintained in all four of the study's clinical measurements.
- Hemoglobin and platelet counts, as well as spleen and liver volumes, remained stable throughout the 12 months of treatment switch to VPRIV
- It is thought that antibodies could indicate an unwanted response to treatment, although further research is needed to confirm this. Learn more about developing antibodies to VPRIV here
- No patients required a higher dose of VPRIV than what they had previously been receiving of imiglucerase
- The investigators of the study concluded that the safety profile was sufficient to transition appropriate patients currently receiving imiglucerase onto VPRIV
AVERAGE INCREASE IN RED BLOOD CELL COUNT
40 patients receiving 15-60 Units/kg VPRIV once every other week for 12 months
AVERAGE % CHANGE FROM STUDY START
Patients receiving 15-60 Units/kg VPRIV once every other week for 12 months
AVERAGE % CHANGE FROM STUDY START
Patients receiving 15-60 Units/kg VPRIV once every other week for 12 months
AVERAGE % CHANGE FROM STUDY START
Patients receiving 15-60 Units/kg VPRIV once every other week for 12 months
n = Number of patients
BL = Baseline (Baseline was defined as being before the first dose in the initial study)
Red blood cell count
Median hemoglobin concentration at baseline:
13.8 g/dL
At 12 months, average
change: -0.1g/dL
Platelet
count
Median platelet count at baseline: 162 × 109/L
At 12 months, average
change: +7.0%
Spleen
volume
Median spleen volume at baseline: 2.5 times greater than normal spleen volume
At 12 months, average
change: -5.6%
Liver
volume
Median liver volume at baseline: 0.8 times greater than normal liver volume
At 12 months, average
change: 0.0%
Median = the middle value in a list of numbers or values
5-Year Long-Term Extension Study
Patients who had previously been treated with imiglucerase and completed the 12-month switch study then had the option to take part in the 5-year long-term extension study. All patients were administered VPRIV via a 60-minute infusion once every other week at the same dose they had received in the 12-month switch study. The study was open-label, which means that all patients and researchers involved knew all participants were receiving VPRIV.
STUDY 4: 5-YEAR LONG-TERM STUDY RESEARCH OBJECTIVES
STUDY 4: 5-YEAR LONG-TERM STUDY RESEARCH OBJECTIVES
Study 3 Overall
VPRIV (40 patients)
VPRIV
15–60 units/kg once every
other week (38 patients)
Primary: To evaluate the long-term safety of VPRIV treatment.
SECONDARY: To evaluate the effects of treatment on red blood cell and platelet counts, and spleen and liver volumes.
After 24 months of VPRIV treatment in this study, patients switching from imiglucerase maintained stability in clinical parameters compared with baseline. These improvements were maintained throughout the 5-year long-term extension study.
AVERAGE INCREASE IN RED BLOOD CELL COUNT
At 12 months, baseline: 13.8 g/dL; average change from the start of Study 3: -0.1 g/dL
At 24 months, baseline: 13.82 g/dL; average change from the start of Study 3: -0.05 g/dL
AVERAGE INCREASE IN PLATELET COUNT
At 12 months, baseline: 162 × 109/L; average change from the start of Study 3: +7.0%
At 24 months, baseline: 164.5 × 109/L; average change from the start of Study 3: 9.03 × 109/L
AVERAGE DECREASE IN SPLEEN VOLUME
At 12 months, baseline: 2.5 times greater than normal spleen volume; average change from the start of Study 3: -5.6%
At 24 months, baseline: 0.821% of body weight; average change from the start of Study 3: -0.110% of body weight
AVERAGE DECREASE IN LIVER VOLUME
At 12 months, baseline: 0.8 times greater than normal liver volume; average change from the start of Study 3: 0.0%
At 24 months, baseline: 2.062% of body weight; average change from the start of Study 3: -0.026% of body weight
n = Number of patients
BL = Baseline (Baseline was defined as being before the first dose in the initial study)
