Trial Outcomes & Findings for Efficacy and Safety of Pegzilarginase in Patients With Arginase 1 Deficiency (NCT NCT03921541)
NCT ID: NCT03921541
Last Updated: 2024-11-19
Results Overview
The primary analysis will test the change in the level of plasma arginine between baseline and completion of week 24 assessments. It will compare the change from baseline in plasma arginine between participants treated with pegzilarginase and those treated with placebo.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
32 participants
Primary outcome timeframe
Baseline through Week 24
Results posted on
2024-11-19
Participant Flow
Participant milestones
| Measure |
Pegzilarginase
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
After completion of the 24-week double-blind treatment period, each subject entered the long term, open-label extension where all subjects received weekly SC or IV pegzilarginase plus individualized disease management
|
Placebo
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
After completion of the 24-week double-blind treatment period, each subject entered the long term, open-label extension where all subjects received weekly SC or IV pegzilarginase plus individualized disease management
|
|---|---|---|
|
Double Blind Treatment Period
STARTED
|
21
|
11
|
|
Double Blind Treatment Period
COMPLETED
|
20
|
11
|
|
Double Blind Treatment Period
NOT COMPLETED
|
1
|
0
|
|
Long Term Extension
STARTED
|
20
|
11
|
|
Long Term Extension
COMPLETED
|
20
|
11
|
|
Long Term Extension
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
| Measure |
Pegzilarginase
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
After completion of the 24-week double-blind treatment period, each subject entered the long term, open-label extension where all subjects received weekly SC or IV pegzilarginase plus individualized disease management
|
Placebo
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
After completion of the 24-week double-blind treatment period, each subject entered the long term, open-label extension where all subjects received weekly SC or IV pegzilarginase plus individualized disease management
|
|---|---|---|
|
Double Blind Treatment Period
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Data not available for 2 subjects in pegzilarginase group.
Baseline characteristics by cohort
| Measure |
Pegzilarginase
n=21 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Total
n=32 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
20 Participants
n=21 Participants
|
9 Participants
n=11 Participants
|
29 Participants
n=32 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=21 Participants
|
2 Participants
n=11 Participants
|
3 Participants
n=32 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=21 Participants
|
0 Participants
n=11 Participants
|
0 Participants
n=32 Participants
|
|
Age, Continuous
|
9.6 years
STANDARD_DEVIATION 6.16 • n=21 Participants
|
12.9 years
STANDARD_DEVIATION 6.77 • n=11 Participants
|
10.7 years
STANDARD_DEVIATION 6.47 • n=32 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=21 Participants
|
4 Participants
n=11 Participants
|
13 Participants
n=32 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=21 Participants
|
7 Participants
n=11 Participants
|
19 Participants
n=32 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=21 Participants
|
0 Participants
n=11 Participants
|
0 Participants
n=32 Participants
|
|
Race (NIH/OMB)
Asian
|
3 Participants
n=21 Participants
|
3 Participants
n=11 Participants
|
6 Participants
n=32 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=21 Participants
|
0 Participants
n=11 Participants
|
0 Participants
n=32 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=21 Participants
|
2 Participants
n=11 Participants
|
2 Participants
n=32 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=21 Participants
|
4 Participants
n=11 Participants
|
14 Participants
n=32 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=21 Participants
|
1 Participants
n=11 Participants
|
2 Participants
n=32 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
7 Participants
n=21 Participants
|
1 Participants
n=11 Participants
|
8 Participants
n=32 Participants
|
|
Age at Diagnosis
|
2.8 years
STANDARD_DEVIATION 4.06 • n=21 Participants
|
4.2 years
STANDARD_DEVIATION 3.07 • n=11 Participants
|
3.3 years
STANDARD_DEVIATION 3.75 • n=32 Participants
|
|
GMFCS Level
I
|
9 Participants
n=21 Participants
|
5 Participants
n=11 Participants
|
14 Participants
n=32 Participants
|
|
GMFCS Level
II
|
9 Participants
n=21 Participants
|
4 Participants
n=11 Participants
|
13 Participants
n=32 Participants
|
|
GMFCS Level
III
|
0 Participants
n=21 Participants
|
0 Participants
n=11 Participants
|
0 Participants
n=32 Participants
|
|
GMFCS Level
IV
|
3 Participants
n=21 Participants
|
2 Participants
n=11 Participants
|
5 Participants
n=32 Participants
|
|
GMFCS Level
V
|
0 Participants
n=21 Participants
|
0 Participants
n=11 Participants
|
0 Participants
n=32 Participants
|
|
Level of Spasticity
None
|
8 Participants
n=21 Participants
|
3 Participants
n=11 Participants
|
11 Participants
n=32 Participants
|
|
Level of Spasticity
Mild
|
7 Participants
n=21 Participants
|
2 Participants
n=11 Participants
|
9 Participants
n=32 Participants
|
|
Level of Spasticity
Moderate
|
5 Participants
n=21 Participants
|
4 Participants
n=11 Participants
|
9 Participants
n=32 Participants
|
|
Level of Spasticity
Severe
|
1 Participants
n=21 Participants
|
2 Participants
n=11 Participants
|
3 Participants
n=32 Participants
|
|
Historical arginine level
|
409.4 micromolar
STANDARD_DEVIATION 114.83 • n=19 Participants • Data not available for 2 subjects in pegzilarginase group.
|
476.1 micromolar
STANDARD_DEVIATION 124.09 • n=11 Participants • Data not available for 2 subjects in pegzilarginase group.
|
433.9 micromolar
STANDARD_DEVIATION 120.68 • n=30 Participants • Data not available for 2 subjects in pegzilarginase group.
|
PRIMARY outcome
Timeframe: Baseline through Week 24Population: Full Analysis Set - all subjects who are randomized and who receive at least 1 dose of blinded study treatment
The primary analysis will test the change in the level of plasma arginine between baseline and completion of week 24 assessments. It will compare the change from baseline in plasma arginine between participants treated with pegzilarginase and those treated with placebo.
Outcome measures
| Measure |
Pegzilarginase
n=21 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Change From Baseline in Plasma Arginine Concentration After 24 Weeks of Treatment
|
0.244 micromolar
Standard Deviation 1.635
|
0.918 micromolar
Standard Deviation 1.371
|
SECONDARY outcome
Timeframe: Baseline through Week 24The Key Secondary outcome measure is the mean change from baseline in the 2 Minute Walk Test.
Outcome measures
| Measure |
Pegzilarginase
n=19 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=10 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Mean Change From Baseline in the Mobility Assessments of the Key Secondary Outcome Measure of the 2 Minute Walk Test
|
7.3 meters
Standard Deviation 30.64
|
2.7 meters
Standard Deviation 19.66
|
SECONDARY outcome
Timeframe: Baseline through Week 24The Key Secondary outcome measure is the mean change from baseline in GMFM-E The Gross Motor Function Measure (GMFM) utilize a 4-point scoring system for each item across dimensions A-E. GMFM-E assesses walking, running, and jumping. The minimum score for GMFM-E is 0; the maximum score is 72, with a higher score representing better gross motor function
Outcome measures
| Measure |
Pegzilarginase
n=20 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Mean Change From Baseline in the Mobility Assessments of the Key Secondary Outcome Measure of GMFM-E
|
4.2 score on a scale
Standard Deviation 7.69
|
-0.4 score on a scale
Standard Deviation 6.20
|
SECONDARY outcome
Timeframe: Baseline and week 24Population: Full Analysis Set
Proportion of participants with plasma arginine levels below 200umol/L (target level set in disease management guidelines) after 24 weeks of treatment.
Outcome measures
| Measure |
Pegzilarginase
n=21 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Proportion of Participants With Plasma Arginine Levels Below Target Guidance
|
19 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Full Analysis Set
Proportion of participants with plasma arginine levels between 40 - 115 umol/L (normal range for plasma arginine) after 24 weeks.
Outcome measures
| Measure |
Pegzilarginase
n=21 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Proportion of Participants With Plasma Arginine Levels in Normal Range
|
19 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline and week 24This analysis will measure the change from baseline in the level of ornithine after 24 weeks of treatment.
Outcome measures
| Measure |
Pegzilarginase
n=15 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=10 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Change in Ornithine
|
1.941 micromolar
Standard Error 1.087
|
0.938 micromolar
Standard Error 1.107
|
SECONDARY outcome
Timeframe: Baseline to week 24This analysis will measure the change from baseline in the level of ARGA after 24 weeks of treatment.
Outcome measures
| Measure |
Pegzilarginase
n=21 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Change in Guanidino Compound-ARGA
|
0.306 micromolar
Standard Error 1.099
|
1.003 micromolar
Standard Error 1.141
|
SECONDARY outcome
Timeframe: Baseline to week 24This analysis will measure the change from baseline in the level of GAA compound after 24 weeks of treatment.
Outcome measures
| Measure |
Pegzilarginase
n=21 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Change in Guanidino Compound - GAA
|
0.481 micromolar
Standard Error 1.111
|
1.030 micromolar
Standard Error 1.157
|
SECONDARY outcome
Timeframe: Baseline to week 24This analysis will measure the change from baseline in the level of GVA compound after 24 weeks of treatment.
Outcome measures
| Measure |
Pegzilarginase
n=21 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Change in Guanidino Compound - GVA
|
0.290 micromolar
Standard Error 1.108
|
0.916 micromolar
Standard Error 1.153
|
SECONDARY outcome
Timeframe: Baseline to week 24This analysis will measure the change from baseline in the level of NAArg compound after 24 weeks of treatment.
Outcome measures
| Measure |
Pegzilarginase
n=21 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Change in Guanidino Compound - NAArg
|
0.289 micromolar
Standard Error 1.140
|
0.956 micromolar
Standard Error 1.200
|
SECONDARY outcome
Timeframe: Baseline to week 24To compare pegzilarginase with placebo with respect to other aspects of mobility. The Gross Motor Function Measure (GMFM) utilize a 4-point scoring system for each item across dimensions A-E. GMFM-D assesses tasks related to standing. The minimum score for GMFM-D is 0; the maximum score is 39 with a higher score representing better gross motor function
Outcome measures
| Measure |
Pegzilarginase
n=20 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Mean Change From Baseline at Week 24 in Other Aspects of Mobility Assessed by GMFM-D
|
2.7 score on a scale
Standard Deviation 3.88
|
0.4 score on a scale
Standard Deviation 0.97
|
SECONDARY outcome
Timeframe: Baseline to week 24To compare pegzilarginase with placebo with respect to other aspects of mobility utilizing the FMS-5 Score. The functional mobility scale (FMS) is a 6-point scale from Level 1 (uses wheelchair, stroller, scooter, shopping cart, wagon, or is carried OR walks for exercise only with highly specialized/ supportive walker OR does limited stepping with substantial support/assistance from another person) to Level 6 (independent walking and running on all surfaces without assistive devices or help from another person) that assesses the need for assistive devices for walks of 3 different lengths: 5 meters, 50 meters, and 500 meters.
Outcome measures
| Measure |
Pegzilarginase
n=20 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Mean Change From Baseline at Week 24 in Other Aspects of Mobility Assessed by the Functional Mobility Scale (FMS)
|
0.1 score on a scale
Standard Deviation 0.39
|
-0.1 score on a scale
Standard Deviation 0.70
|
SECONDARY outcome
Timeframe: Baseline to week 24To compare pegzilarginase with placebo with respect to other aspects of mobility utilizing the FMS-50 Score. The functional mobility scale (FMS) is a 6-point scale from Level 1 (uses wheelchair, stroller, scooter, shopping cart, wagon, or is carried OR walks for exercise only with highly specialized/ supportive walker OR does limited stepping with substantial support/assistance from another person) to Level 6 (independent walking and running on all surfaces without assistive devices or help from another person) that assesses the need for assistive devices for walks of 3 different lengths: 5 meters, 50 meters, and 500 meters.
Outcome measures
| Measure |
Pegzilarginase
n=19 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Mean Change From Baseline at Week 24 in Other Aspects of Mobility Assessed by the Functional Mobility Scale (FMS)
|
0.2 score on a scale
Standard Deviation 0.42
|
0.1 score on a scale
Standard Deviation 0.83
|
SECONDARY outcome
Timeframe: Baseline to week 24To compare pegzilarginase with placebo with respect to other aspects of mobility utilizing the FMS-500 Score. The functional mobility scale (FMS) is a 6-point scale from Level 1 (uses wheelchair, stroller, scooter, shopping cart, wagon, or is carried OR walks for exercise only with highly specialized/ supportive walker OR does limited stepping with substantial support/assistance from another person) to Level 6 (independent walking and running on all surfaces without assistive devices or help from another person) that assesses the need for assistive devices for walks of 3 different lengths: 5 meters, 50 meters, and 500 meters.
Outcome measures
| Measure |
Pegzilarginase
n=18 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Mean Change From Baseline at Week 24 in Other Aspects of Mobility Assessed by the Functional Mobility Scale (FMS)
|
0.1 score on a scale
Standard Deviation 0.24
|
0.2 score on a scale
Standard Deviation 0.40
|
SECONDARY outcome
Timeframe: Baseline to week 24To compare pegzilarginase with placebo with respect to other aspects of mobility. The Gillette Functional Assessment Questionnaire (GFAQ) is a parent/caregiver assessment consisting of a single question describing a child's ability to walk using a 10-point scale from Level 1 (cannot take any steps at all) to Level 10 (walks, runs, and climbs on uneven terrain and does stairs without difficulty or assistance; is typically able to keep up with peers).
Outcome measures
| Measure |
Pegzilarginase
n=20 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Mean Change From Baseline at Week 24 in Other Aspects of Mobility Assessed by the Gillette Functional Assessment Questionnaire (GFAQ)
|
0.1 score on a scale
Standard Deviation 0.79
|
-0.3 score on a scale
Standard Deviation 0.90
|
SECONDARY outcome
Timeframe: Baseline to week 24To compare pegzilarginase with placebo with respect to adaptive behavior. The Vineland Adaptive Behavior Scales (VABS-II) is a scale designed to measure adaptive behavior of individuals from birth to age 90 years. The VABS-II contains 4 domains: communication, daily living skills, socialization, and motor skills. The domains are made up of 11 subdomains in which the scores are added to form the domain composite scores. The 4 domain composite scores then combine to form the adaptive behavior composite for those individuals aged birth to 6 years 11 months. Three domain composite scores (communication, daily living skills, and socialization) combine to form the adaptive behavior composite for those ages 7 through 90 years. The VABS-II scoring system describes adequate adaptive behavior by subdomain as 13 to 17 and 86 to 114 for the composite score, with higher scores indicating better adaptive functioning.
Outcome measures
| Measure |
Pegzilarginase
n=18 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=10 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Mean Change From Baseline at Week 24 in Adaptive Behavior Assessed Using the Vineland Adaptive Behavior Scales (VABS)-II
|
1.4 score on a scale
Standard Deviation 16.54
|
-1.6 score on a scale
Standard Deviation 8.78
|
SECONDARY outcome
Timeframe: Reporting will be from signing consent through follow-up (Baseline to Week 24)Number of participants developing treatment related adverse events.
Outcome measures
| Measure |
Pegzilarginase
n=21 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Evaluate Safety of Pegzilarginase
|
18 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: Baseline to week 24The proportion of participants who develop (ADA) anti-drug antibodies to pegzilarginase will be measured over the period of the clinical trial.
Outcome measures
| Measure |
Pegzilarginase
n=21 Participants
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 Participants
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Evaluate Immunogenicity of Pegzilarginase
|
4 Participants
|
3 Participants
|
Adverse Events
Pegzilarginase
Serious events: 4 serious events
Other events: 18 other events
Deaths: 0 deaths
Placebo
Serious events: 4 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pegzilarginase
n=21 participants at risk
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 participants at risk
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Metabolism and nutrition disorders
Hyperammonaemia
|
9.5%
2/21 • Baseline to 24 weeks
|
27.3%
3/11 • Baseline to 24 weeks
|
|
Metabolism and nutrition disorders
Hyperammonaemic encephalopathy
|
4.8%
1/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Gastrointestinal disorders
Vomiting
|
4.8%
1/21 • Baseline to 24 weeks
|
0.00%
0/11 • Baseline to 24 weeks
|
Other adverse events
| Measure |
Pegzilarginase
n=21 participants at risk
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
Pegzilarginase: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
Placebo
n=11 participants at risk
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
Placebo: Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
|
|---|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/21 • Baseline to 24 weeks
|
27.3%
3/11 • Baseline to 24 weeks
|
|
Gastrointestinal disorders
Constipation
|
14.3%
3/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/21 • Baseline to 24 weeks
|
36.4%
4/11 • Baseline to 24 weeks
|
|
Gastrointestinal disorders
Vomiting
|
23.8%
5/21 • Baseline to 24 weeks
|
27.3%
3/11 • Baseline to 24 weeks
|
|
General disorders
Pyrexia
|
19.0%
4/21 • Baseline to 24 weeks
|
0.00%
0/11 • Baseline to 24 weeks
|
|
Hepatobiliary disorders
Hepatic cytolysis
|
0.00%
0/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Infections and infestations
Nasopharyngitis
|
9.5%
2/21 • Baseline to 24 weeks
|
0.00%
0/11 • Baseline to 24 weeks
|
|
Injury, poisoning and procedural complications
Fall
|
9.5%
2/21 • Baseline to 24 weeks
|
0.00%
0/11 • Baseline to 24 weeks
|
|
Investigations
Alanine aminotransferase increased
|
9.5%
2/21 • Baseline to 24 weeks
|
0.00%
0/11 • Baseline to 24 weeks
|
|
Investigations
Ammonia increased
|
14.3%
3/21 • Baseline to 24 weeks
|
18.2%
2/11 • Baseline to 24 weeks
|
|
Investigations
Aspartate aminotransferase increased
|
9.5%
2/21 • Baseline to 24 weeks
|
0.00%
0/11 • Baseline to 24 weeks
|
|
Investigations
Blood potassium decreased
|
0.00%
0/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Investigations
Body temperature increased
|
0.00%
0/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Investigations
Cardiac murmur
|
0.00%
0/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Metabolism and nutrition disorders
Decreased appetite
|
0.00%
0/21 • Baseline to 24 weeks
|
18.2%
2/11 • Baseline to 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Osteochondrosis
|
0.00%
0/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Nervous system disorders
Dizziness
|
9.5%
2/21 • Baseline to 24 weeks
|
0.00%
0/11 • Baseline to 24 weeks
|
|
Nervous system disorders
Headache
|
9.5%
2/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Nervous system disorders
Lethargy
|
0.00%
0/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Psychiatric disorders
Aggression
|
0.00%
0/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Psychiatric disorders
Generalized anxiety disorder
|
0.00%
0/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Psychiatric disorders
Mood altered
|
0.00%
0/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
19.0%
4/21 • Baseline to 24 weeks
|
18.2%
2/11 • Baseline to 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
9.5%
2/21 • Baseline to 24 weeks
|
0.00%
0/11 • Baseline to 24 weeks
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
9.5%
2/21 • Baseline to 24 weeks
|
0.00%
0/11 • Baseline to 24 weeks
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
0.00%
0/21 • Baseline to 24 weeks
|
9.1%
1/11 • Baseline to 24 weeks
|
Additional Information
Vice President, Head of Global Integrated Evidence / Global Head of Genetic and Metabolic Diseases
Immedica Pharma AB
Phone: +46 8 533 39 500
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60