A research study in patients with Arginase I Deficiency to investigate the safety of a new drug and its ability to lower arginine levels

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 40

Inclusion Criteria

1. 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.
2. 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 s pathogenic variant, or reduced RBC arginase
activity. For entry into this study, subjects must also fulfill the following
plasma arginine criteria:
a. 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.
b. If a subject is re-screened, the only values that are considered for eligibility assessment are those in the current screening period.
3. Subjects must be = 2 years of age on the date of informed consent /
assent.4. The subject must be assessable for clinically meaningful withinsubject
change (clinical response) on at least 1 component of 1
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 1 component as defined in the
protocol.
5. 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
essential amino acid supplementation.
6. 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.
7. 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).

Are the trial subjects under 18? yes
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Hyperammonemic episode (defined as an event in which a subject has an ammonia level =100 uM 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.
2. Active infection requiring anti-infective therapy within 3 weeks prior to first dose.
3. Known active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
4. Extreme mobility deficit, defined as either the inability to be assessed on the GFAQ or a score of 1 on the GFAQ.
5. 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).
6. Has participated in a previous interventional study with pegzilarginase.
7. 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.
8. Subject is being treated with botulinum-toxin containing regimens or
plans to initiate such regimens during the double-blind or blinded followup
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.
9. 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.
10. Previous liver or hematopoietic transplant procedure.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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