Purpose

CAEB1102-300A is a multi-center randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of pegzilarginase in patients with ARG1-D. This study will consist of a screening period; a randomized, double-blind treatment period; a long-term extension; and a follow up visit for final safety assessments.

Conditions

Eligibility

Eligible Ages
Over 2 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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. For entry into this study, subjects must also fulfill the following plasma arginine criterion:
  3. The average of all measured values of plasma arginine during the screening period prior to the randomization visit (Visit 1, Study Day 0) is ≥ 250 µmol/L
  4. If a subject is re-screened, the only values that are considered for eligibility assessment are those in the current screening period
  5. Subjects must be ≥ 2 years of age on the date of informed consent/assent
  6. 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 endpoint. To be considered assessable, the subject must be able to complete the assessment, and must have a baseline deficit in the specific component as defined in the protocol
  7. Have received documented confirmation from the investigator and/or dietician that the subject is capable of maintaining their diet in accordance with dietary information presented in the protocol, i.e., is capable of maintaining their current level of protein consumption including natural protein and essential amino acid supplementation
  8. Subjects receiving ammonia scavenger therapy, anti-epileptic drugs, and/or medications for spasticity (e.g., 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
  9. Female and male subjects may participate. Female subjects of child-bearing 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 (female), 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); or intrauterine hormone-releasing system (IUS)

Exclusion Criteria

  1. Hyperammonemic episode (defined as an event in which a subject has an ammonia level > 100 umol/L 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 in 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 (e.g., 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 follow-up portions of the study or received surgical or botulinum-toxin treatment within last 6 months for spasticity related complications
  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 on this study
  10. Previous liver or hematopoietic transplant procedure.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Pegzilarginase
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
  • Drug: Pegzilarginase
    Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
    Other names:
    • Co-ArgI-PEG; AEB1102
  • Drug: Pegzilarginase
    Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
    Other names:
    • Co-ArgI-PEG; AEB1102
Placebo Comparator
Placebo
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
  • Drug: Placebo
    Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
Experimental
Pegzilarginase Long Term Extension
After 24 weeks, weekly IV infusions of pegzilarginase plus individualized disease management for for an additional 150 weeks
  • Drug: Pegzilarginase
    Individualized disease management which includes severe protein restriction, essential amino acid supplementation and the ammonia scavengers when indicated
    Other names:
    • Co-ArgI-PEG; AEB1102

Recruiting Locations

Children's National and nearby locations

Children's National Medical Center
Washington, District of Columbia 20010
Contact:
Nicholas Ah Mew, MD

More Details

NCT ID
NCT03921541
Status
Recruiting
Sponsor
Aeglea Biotherapeutics

Study Contact

Aeglea Clinical Department
1.855.509.9921
raredisease@aegleabio.com

Detailed Description

CAEB1102-300A is a multi-center randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of pegzilarginase in patients with ARG1-D. This study will consist of a screening period; a randomized, double-blind treatment period; a long-term extension; and a follow up visit for final safety assessments.

Subjects will be randomized to treatment following completion of all screening assessments and confirmation of study eligibility in a 2:1 ratio to receive weekly IV infusions of pegzilarginase plus individualized disease management (IDM) or placebo plus IDM during the 24-week double blind treatment period. After completion of the 24-week double-blind treatment period, each subject will enter the long term, open-label extension, the first 8 weeks of which are blinded. During the long-term extension, all subjects receive pegzilarginase plus IDM.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.