Efficacy and Safety of Pegzilarginase in Patients With Ar... | NCT03921541

NCT03921541

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Pegzilarginase	Experimental	Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks	Drug: Pegzilarginase
Placebo	Placebo Comparator	Weekly IV infusions of placebo plus individualized disease management for 24 weeks	Drug: Placebo
Pegzilarginase Long Term Extension	Experimental	After completion of 24 weeks DB treatment, weekly IV infusions of pegzilarginase plus individualized disease management for an additional 150 weeks, with the option to receive treatment by SC after 8 weeks of the LTE study.	Drug: Pegzilarginase

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Pegzilarginase	Drug	Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated	Pegzilarginase

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Plasma Arginine Concentration After 24 Weeks of 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.	Baseline through Week 24

Secondary Outcomes

Measure	Description	Time Frame
Mean Change From Baseline in the Mobility Assessments of the Key Secondary Outcome Measure of the 2 Minute Walk Test	The Key Secondary outcome measure is the mean change from baseline in the 2 Minute Walk Test.	Baseline through Week 24
Mean Change From Baseline in the Mobility Assessments of the Key Secondary Outcome Measure of GMFM-E

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subjects are eligible to be included in the study only if all the following criteria apply:

The subject and/or parent/guardian provides written informed consent/assent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
A current diagnosis of ARG1 D as documented in medical records, which must include 1 of the following: elevated plasma arginine levels, a mutation analysis that results in a pathogenic variant, or reduced RBC arginase activity. For entry into this study, subjects must also fulfill the following plasma arginine criteria:
1. The average of all measured values of plasma arginine during the screening period prior to the randomization visit (Visit 1, Study Day 1) is ≥ 250 µmol/L
2. If a subject is re-screened, the only values that are considered for eligibility assessment are those in the current screening period
Subjects must be ≥ 2 years of age on the date of informed consent/assent
The subject must be assessable for clinically meaningful within-subject change (clinical response) on at least one component of one assessment included in the key secondary/other secondary endpoints. To be considered assessable, the subject must be able to complete the assessment, and must have a baseline deficit in at least one component as defined in the protocol
Have received documented confirmation from the investigator and/or dietician that the subject can maintain their diet in accordance with dietary information presented in the protocol, ie, can maintain the current level of protein consumption, including natural protein and EAA supplementation
Subjects receiving ammonia scavenger therapy, anti-epileptic drugs, and/or medications for spasticity (eg, baclofen) must be on a stable dose of the medication for at least 4 weeks prior to randomization and be willing to remain on a stable dose during the double-blind portion and blinded follow-up portions of the study
Female and male subjects may participate. Female subjects of childbearing potential must have a negative serum pregnancy test during the screening period before receiving the first dose of study treatment, and a negative urine pregnancy test on the day of the first dose, prior to the first dose. If the subject (male or female) is engaging in sexual activity that could lead to pregnancy, must be surgically sterile, postmenopausal (no menses for 12 months without an alternative medical cause or a high FSH level in the postmenopausal range in women not using hormonal contraception or hormonal replacement therapy), or must agree to use a highly effective method of birth control during the study and for a minimum of 30 days after the last study drug administration. Highly effective methods of contraception include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; progesterone-only hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); or abstinence (refraining from heterosexual intercourse during the entire period of risk associated with study treatment).

Exclusion Criteria:

Hyperammonemic episode (defined as an event in which a subject has an ammonia level ≥100 µM with one or more symptoms related to hyperammonemia requiring hospitalization or emergency room management) within the 6 weeks before the first dose of study drug is administered
Active infection requiring anti-infective therapy within 3 weeks prior to first dose
Known active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
Extreme mobility deficit, defined as either the inability to be assessed on the GFAQ or a score of 1 on the GFAQ
Other medical conditions or comorbidities that, in the opinion of the investigator would interfere with study compliance or data interpretation (eg, severe intellectual disability precluding required study assessments)
Has participated in a previous interventional study with pegzilarginase
Has a history of hypersensitivity to polyethylene glycol (PEG) that, in the judgment of the investigator, puts the subject at unacceptable risk for adverse events
Subject is being treated with botulinum toxin-containing regimens or plans to initiate such regimens during the double-blind or blinded follow-up portions of the study or received surgical or botulinum-toxin treatment for spasticity-related complications within the 16 weeks prior to the first dose of study treatment in this study
Is currently participating in another therapeutic clinical trial or has received any investigational agent within 30 days (or 5 half-lives whichever is longer) prior to the first dose of study treatment in this study
Previous liver or hematopoietic transplant procedure.

Contacts/Locations Module

Name	Affiliation	Role
Cortney Caudill	Aeglea BioTherapeutics, Inc.	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Harvey Pediatrics		Rogers	Arkansas	72758	United States
Children's Hospital of Orange County

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
38292042	Derived	Russo RS, Gasperini S, Bubb G, Neuman L, Sloan LS, Diaz GA, Enns GM; PEACE Investigators. Efficacy and safety of pegzilarginase in arginase 1 deficiency (PEACE): a phase 3, randomized, double-blind, placebo-controlled, multi-centre trial. EClinicalMedicine. 2024 Jan 12;68:102405. doi: 10.1016/j.eclinm.2023.102405. eCollection 2024 Feb.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Dec 11, 2020	Sep 2, 2024

Derived Section

Miscellaneous Info Module

Submission Tracking

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Pegzilarginase Long Term Extension

FG00021 subjects
FG00111 subjects

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	Pegzilarginase	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
BG001	Placebo	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
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	OG0000.244± 1.635 OG0010.918± 1.371

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Mixed Models Analysis		<0.0001														Superiority

Secondary

Mean Change From Baseline in the Mobility Assessments of the Key Secondary Outcome Measure of the 2 Minute Walk Test

The Key Secondary outcome measure is the mean change from baseline in the 2 Minute Walk Test.

Posted

Mean

Standard Deviation

meters

Baseline through Week 24

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Units	Counts
Participants	OG000

Secondary

Mean Change From Baseline in the Mobility Assessments of the Key Secondary Outcome Measure of GMFM-E

The 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

Posted

Mean

Standard Deviation

score on a scale

Baseline through Week 24

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Units	Counts
Participants

Secondary

Proportion of Participants With Plasma Arginine Levels Below Target Guidance

Proportion of participants with plasma arginine levels below 200umol/L (target level set in disease management guidelines) after 24 weeks of treatment.

Full Analysis Set

Posted

Count of Participants

Participants

Baseline and week 24

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Units	Counts
Participants	OG000

Secondary

Proportion of Participants With Plasma Arginine Levels in Normal Range

Proportion of participants with plasma arginine levels between 40 - 115 umol/L (normal range for plasma arginine) after 24 weeks.

Full Analysis Set

Posted

Count of Participants

Participants

Baseline to Week 24

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Units	Counts
Participants	OG000

Secondary

Change in Ornithine

This analysis will measure the change from baseline in the level of ornithine after 24 weeks of treatment.

Posted

Geometric Least Squares Mean

Standard Error

micromolar

Baseline and week 24

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Units	Counts
Participants	OG000

Secondary

Change in Guanidino Compound-ARGA

This analysis will measure the change from baseline in the level of ARGA after 24 weeks of treatment.

Posted

Geometric Least Squares Mean

Standard Error

micromolar

Baseline to week 24

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Units	Counts
Participants	OG000

Secondary

Change in Guanidino Compound - GAA

This analysis will measure the change from baseline in the level of GAA compound after 24 weeks of treatment.

Posted

Geometric Least Squares Mean

Standard Error

micromolar

Baseline to week 24

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Units	Counts
Participants	OG000

Secondary

Change in Guanidino Compound - GVA

This analysis will measure the change from baseline in the level of GVA compound after 24 weeks of treatment.

Posted

Geometric Least Squares Mean

Standard Error

micromolar

Baseline to week 24

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Units	Counts
Participants	OG000

Secondary

Change in Guanidino Compound - NAArg

This analysis will measure the change from baseline in the level of NAArg compound after 24 weeks of treatment.

Posted

Geometric Least Squares Mean

Standard Error

micromolar

Baseline to week 24

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Units	Counts
Participants	OG000

Secondary

Mean Change From Baseline at Week 24 in Other Aspects of Mobility Assessed by GMFM-D

To 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

Posted

Mean

Standard Deviation

score on a scale

Baseline to week 24

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Units	Counts
Participants

Secondary

Mean Change From Baseline at Week 24 in Other Aspects of Mobility Assessed by the Functional Mobility Scale (FMS)

To 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.

Posted

Mean

Standard Deviation

score on a scale

Baseline to week 24

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Secondary

Mean Change From Baseline at Week 24 in Other Aspects of Mobility Assessed by the Functional Mobility Scale (FMS)

To compare pegzilarginase with placebo with respect to other aspects of mobility utilizing the FMS-50 Score.

Posted

Mean

Standard Deviation

score on a scale

Baseline to week 24

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Secondary

Mean Change From Baseline at Week 24 in Other Aspects of Mobility Assessed by the Functional Mobility Scale (FMS)

To compare pegzilarginase with placebo with respect to other aspects of mobility utilizing the FMS-500 Score.

Posted

Mean

Standard Deviation

score on a scale

Baseline to week 24

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Secondary

Mean Change From Baseline at Week 24 in Other Aspects of Mobility Assessed by the Gillette Functional Assessment Questionnaire (GFAQ)

To 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).

Posted

Mean

Standard Deviation

score on a scale

Baseline to week 24

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Units	Counts

Secondary

Mean Change From Baseline at Week 24 in Adaptive Behavior Assessed Using the Vineland Adaptive Behavior Scales (VABS)-II

To 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.

Posted

Mean

Standard Deviation

score on a scale

Baseline to week 24

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Secondary

Evaluate Safety of Pegzilarginase

Number of participants developing treatment related adverse events.

Posted

Count of Participants

Participants

Reporting will be from signing consent through follow-up (Baseline to Week 24)

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Units	Counts
Participants	OG000

Secondary

Evaluate Immunogenicity of Pegzilarginase

The proportion of participants who develop (ADA) anti-drug antibodies to pegzilarginase will be measured over the period of the clinical trial.

Posted

Count of Participants

Participants

Baseline to week 24

ID	Title	Description
OG000	Pegzilarginase	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
OG001	Placebo	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

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pegzilarginase	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	0	21	4	21	18	21
EG001	Placebo	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	0	11	4	11	11	11

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Hyperammonaemia	Metabolism and nutrition disorders	Systematic Assessment	EG0002 affected21 at risk EG0013 affected11 at risk
Hyperammonaemic encephalopathy	Metabolism and nutrition disorders	Systematic Assessment	EG0001 affected21 at risk EG0011 affected11 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0001 affected21 at risk EG0010 affected11 at risk

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Abdominal Pain	Gastrointestinal disorders	Systematic Assessment	EG0000 affected21 at risk EG0013 affected11 at risk
Constipation	Gastrointestinal disorders	Systematic Assessment	EG0003 affected21 at risk EG0011 affected11 at risk
Diarrhoea	Gastrointestinal disorders	Systematic Assessment	EG0000 affected21 at risk EG0011 affected11 at risk
Nausea	Gastrointestinal disorders	Systematic Assessment	EG0000 affected21 at risk EG0014 affected11 at risk
Vomiting	Gastrointestinal disorders	Systematic Assessment	EG0005 affected21 at risk EG0013 affected11 at risk
Pyrexia	General disorders	Systematic Assessment	EG0004 affected21 at risk EG0010 affected11 at risk
Hepatic cytolysis	Hepatobiliary disorders	Systematic Assessment	EG0000 affected21 at risk EG0011 affected11 at risk
Nasopharyngitis	Infections and infestations	Systematic Assessment	EG0002 affected21 at risk EG0010 affected11 at risk
Fall	Injury, poisoning and procedural complications	Systematic Assessment	EG0002 affected21 at risk EG0010 affected11 at risk
Alanine aminotransferase increased	Investigations	Systematic Assessment	EG0002 affected21 at risk EG0010 affected11 at risk
Ammonia increased	Investigations	Systematic Assessment	EG0003 affected21 at risk EG0012 affected11 at risk
Aspartate aminotransferase increased	Investigations	Systematic Assessment	EG0002 affected21 at risk EG0010 affected11 at risk
Blood potassium decreased	Investigations	Systematic Assessment	EG0000 affected21 at risk EG0011 affected11 at risk
Body temperature increased	Investigations	Systematic Assessment	EG0000 affected21 at risk EG0011 affected11 at risk
Cardiac murmur	Investigations	Systematic Assessment	EG0000 affected21 at risk EG0011 affected11 at risk
Decreased appetite	Metabolism and nutrition disorders	Systematic Assessment	EG0000 affected21 at risk EG0012 affected11 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected21 at risk EG0011 affected11 at risk
Osteochondrosis	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected21 at risk EG0011 affected11 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	Systematic Assessment	EG0000 affected21 at risk EG0011 affected11 at risk
Dizziness	Nervous system disorders	Systematic Assessment	EG0002 affected21 at risk EG0010 affected11 at risk
Headache	Nervous system disorders	Systematic Assessment	EG0002 affected21 at risk EG0011 affected11 at risk
Lethargy	Nervous system disorders	Systematic Assessment	EG0000 affected21 at risk EG0011 affected11 at risk
Aggression	Psychiatric disorders	Systematic Assessment	EG0000 affected21 at risk EG0011 affected11 at risk
Generalized anxiety disorder	Psychiatric disorders	Systematic Assessment	EG0000 affected21 at risk EG0011 affected11 at risk
Mood altered	Psychiatric disorders	Systematic Assessment	EG0000 affected21 at risk EG0011 affected11 at risk
Cough	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0004 affected21 at risk EG0012 affected11 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected21 at risk EG0011 affected11 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0000 affected21 at risk EG0011 affected11 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	Systematic Assessment	EG0002 affected21 at risk EG0010 affected11 at risk
Pruritus	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0002 affected21 at risk EG0010 affected11 at risk
Rash	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected21 at risk EG0011 affected11 at risk
Skin exfoliation	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected21 at risk EG0011 affected11 at risk

Point of Contact

Title	Organization	Phone	Extension	Email
Vice President, Head of Global Integrated Evidence / Global Head of Genetic and Metabolic Diseases	Immedica Pharma AB	+46 8 533 39 500		Clinical@immedica.com

First MCP Posted Date

ID	Term
D020162	Hyperargininemia

Ancestor Terms

ID	Term
D056806	Urea Cycle Disorders, Inborn
D020739	Brain Diseases, Metabolic, Inborn
D001928	Brain Diseases, Metabolic
D001927	Brain Diseases
D002493	Central Nervous System Diseases
D009422	Nervous System Diseases
D000592	Amino Acid Metabolism, Inborn Errors
D008661	Metabolism, Inborn Errors
D030342	Genetic Diseases, Inborn
D009358	Congenital, Hereditary, and Neonatal Diseases and Abnormalities
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

Units	Counts
Participants	OG00020 OG00111

Units	Counts
Participants	OG00019 OG00111

Units	Counts
Participants	OG00018 OG00111