Arginase I DeficiencyPhase 1/2NCT02488044
A Phase 1/2 Study of AEB1102 in Patients With Arginase I Deficiency
A Phase 1/2 study testing AEB1102 in people with Arginase I Deficiency and Hyperargininemia, run by Aeglea Biotherapeutics at 9 sites in 4 countries.
Trial summary
A Phase 1/2 Open-label Study in Patients with Arginase I Deficiency to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous AEB1102. This study is designed to evaluate the safety and tolerability of IV administration of AEB1102 for the treatment of pediatric and adult patients with Arginase I… Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Arginase I Deficiency, Hyperargininemia
- What is being tested?
- AEB1102
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 9 sitesin 4 countries
- Study dates
- Jun 2016to Feb 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Documented diagnosis of Arginase I deficiency
- Adequate organ function: Hgb ≥ 10 g/dL, ANC ≥ 1.5 x 109/L, plt count ≥ 100,000/µL; liver transaminase levels ≤ 2.5x ULN, total bilirubin ≤ 2.0 mg/dL; serum creatinine <1.5 x ULN
- If female and of child-bearing potential, has a negative serum pregnancy test within 7 days before enrollment
- If a sexually active (male or female), must be surgically sterile, post-menopausal (female), or must agree to use a physician-approved method of birth control during the study and for a minimum of 30 days after the last study drug administration
- Patient or legal guardian is able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures and continuation of prescribed diet without modification) prior to any screening procedures
Who cannot join
- Transfusion of ≥ 2 u RBC within 60 days
- Active infection requiring systemic treatment
- Known infection with HIV, Hep B or Hep C
- Severe hyperammonemia requiring hospitalization within 14 days. Had more than one episode of hyperammonemia requiring hospitalization within the 30 days prior to enrollment.
- Current uncontrolled hyperammonemia
- Has a history of hypersensitivity to PEG or any other component of the AEB1102 (Co-ArgI-PEG) formulation
Show all 9Show fewer
- If female, is lactating or breast feeding
- PART 2 INCLUSION CRITERION:
- 1. Did not experience any safety or tolerability event in Part 1 which would preclude continued participation and dosing of AEB1102
Trial locations and contacts
9 sites in 4 countries.
9 sites in 4 countries
United States6 sites
UTSW
Dallas, Texas, 75390
Children's Hospital of Michigan
Detroit, Michigan, 48201
University of Florida
Gainesville, Florida, 32611
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Seattle Children's Hospital
Seattle, Washington, 98105
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: A Phase 1/2 Open-label Study in Patients With Arginase I Deficiency to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous AEB1102
A Phase 1/2 Open-label Study in Patients with Arginase I Deficiency to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous AEB1102. This study is designed to evaluate the safety and tolerability of IV administration of AEB1102 for the treatment of pediatric and adult patients with Arginase I deficiency and hyperargininemia. This study will be conducted in 2 parts: Part 1 (Single Ascending Dose Escalation) and Part 2 (Repeated Dosing). Each part will be preceded by a baseline assessment of arginine levels. All patients who participate in Part 1 may continue AEB1102 dosing in Part 2 if they qualify for continued dosing. A data safety monitoring board (DSMB) will provide independent review of study safety data and recommend whether the sponsor should continue the study as planned, modify the study protocol, or discontinue the study.
- Conditions
- Arginase I Deficiency, Hyperargininemia
- Being tested
- AEB1102
- Medical subject headings
- Hyperargininemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AEB1102Drug
Also called Co-ArgI-PEG
modified human arginase I
| Study group | Role | What they receive |
|---|---|---|
| AEB1102 | Experimental | AEB1102, modified human Arginase I administered IV Part 1 Each patient may receive up to 7 doses given up to every other week over a maximum of 14 weeks.
Part 2 Each patient will receive up to 8 weeks of repeat-dose therapy. Receives: Drug: AEB1102 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects with adverse events
Includes significant changes in hematology, chemistry and coagulation laboratory studies as well as in physical exam and vital signs
Measured: weekly throughout the study, up to 14 weeks
Secondary outcomes (3)
Number of subjects with a decrease from baseline in plasma arginine level
Measured: Baseline to 2, 4, 6, 8 weeks
Pharmacokinetic profile including Cmax, AUC, Tmax, T1/2 for each subject
Measured: At 15 min, 1, 2, 4, 8, 12, 24, 48, 72, and 120 hours following dose escalation
Number of subjects with a decrease from baseline in plasma guanidino compound levels
Measured: Baseline to 2, 4, 6, 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2015 (estimated)
- Study startJun 2016
- Primary completionFeb 2019
- Study completionFeb 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Arginase I DeficiencyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aeglea Biotherapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Josie Gayton, Study director, Aeglea Biotherapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02488044
- Sponsor's protocol ID
- CAEB1102-101A
- Status last verified
- Jun 2019
- First submitted
- 29 Jun 2015
- Last updated
- 12 Jun 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Crombez EA, Cederbaum SD. Hyperargininemia due to liver arginase deficiency. Mol Genet Metab. 2005 Mar;84(3):243-51. doi: 10.1016/j.ymgme.2004.11.004. Epub 2004 Dec 19.
PubMed 15694174Glazer ES, Stone EM, Zhu C, Massey KL, Hamir AN, Curley SA. Bioengineered human arginase I with enhanced activity and stability controls hepatocellular and pancreatic carcinoma xenografts. Transl Oncol. 2011 Jun;4(3):138-46. doi: 10.1593/tlo.10265. Epub 2011 Jun 1.
PubMed 21633669Diaz GA, Schulze A, McNutt MC, Leao-Teles E, Merritt JL 2nd, Enns GM, Batzios S, Bannick A, Zori RT, Sloan LS, Potts SL, Bubb G, Quinn AG. Clinical effect and safety profile of pegzilarginase in patients with arginase 1 deficiency. J Inherit Metab Dis. 2021 Jul;44(4):847-856. doi: 10.1002/jimd.12343. Epub 2021 Jan 26.
PubMed 33325055
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2 Open-label Study in Patients With Arginase I Deficiency to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous AEB1102
- ClinicalTrials.gov ID
- NCT02488044
- Acronym / sponsor ID
- CAEB1102-101A
- Conditions
- Arginase I Deficiency, Hyperargininemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Aeglea BiotherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Jun 2016
- Primary completion
- Feb 2019 (actual)
- Study completion
- Feb 2019 (actual)
- First posted
- 2 Jul 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
A Phase 1/2 Open-label Study in Patients with Arginase I Deficiency to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous AEB1102. This study is designed to evaluate the safety and tolerability of IV administration of AEB1102 for the treatment of pediatric and adult patients with Arginase I deficiency and hyperargininemia. This study will be conducted in 2 parts: Part 1 (Single Ascending Dose Escalation) and Part 2 (Repeated Dosing). Each part will be preceded by a baseline assessment of arginine levels. All patients who participate in Part 1 may continue AEB1102 dosing in Part 2 if they qualify for continued dosing. A data safety monitoring board (DSMB) will provide independent review of study safety data and recommend whether the sponsor should continue the study as planned, modify the study protocol, or discontinue the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AEB1102 | Experimental | Drug: AEB1102AEB1102, modified human Arginase I administered IV Part 1 Each patient may receive up to 7 doses given up to every other week over a maximum of 14 weeks. Part 2 Each patient will receive up to 8 weeks of repeat-dose therapy. |
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Documented diagnosis of Arginase I deficiency
- Adequate organ function: Hgb ≥ 10 g/dL, ANC ≥ 1.5 x 109/L, plt count ≥ 100,000/µL; liver transaminase levels ≤ 2.5x ULN, total bilirubin ≤ 2.0 mg/dL; serum creatinine <1.5 x ULN
- If female and of child-bearing potential, has a negative serum pregnancy test within 7 days before enrollment
- If a sexually active (male or female), must be surgically sterile, post-menopausal (female), or must agree to use a physician-approved method of birth control during the study and for a minimum of 30 days after the last study drug administration
- Patient or legal guardian is able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures and continuation of prescribed diet without modification) prior to any screening procedures
Key exclusion criteria (9 listed)
- Transfusion of ≥ 2 u RBC within 60 days
- Active infection requiring systemic treatment
- Known infection with HIV, Hep B or Hep C
- Severe hyperammonemia requiring hospitalization within 14 days. Had more than one episode of hyperammonemia requiring hospitalization within the 30 days prior to enrollment.
- Current uncontrolled hyperammonemia
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AEB1102Also: Co-ArgI-PEGmodified human arginase I | Drug | AEB1102 |
Primary outcome
Number of subjects with adverse events
Time frame: weekly throughout the study, up to 14 weeks
Includes significant changes in hematology, chemistry and coagulation laboratory studies as well as in physical exam and vital signs
3 secondary outcomes
Number of subjects with a decrease from baseline in plasma arginine level
Time frame: Baseline to 2, 4, 6, 8 weeks
Pharmacokinetic profile including Cmax, AUC, Tmax, T1/2 for each subject
Time frame: At 15 min, 1, 2, 4, 8, 12, 24, 48, 72, and 120 hours following dose escalation
Number of subjects with a decrease from baseline in plasma guanidino compound levels
Time frame: Baseline to 2, 4, 6, 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2019.
- Background: PubMed 15694174Crombez EA, Cederbaum SD. Hyperargininemia due to liver arginase deficiency. Mol Genet Metab. 2005 Mar;84(3):243-51. doi: 10.1016/j.ymgme.2004.11.004. Epub 2004 Dec 19.
- Background: PubMed 21633669Glazer ES, Stone EM, Zhu C, Massey KL, Hamir AN, Curley SA. Bioengineered human arginase I with enhanced activity and stability controls hepatocellular and pancreatic carcinoma xenografts. Transl Oncol. 2011 Jun;4(3):138-46. doi: 10.1593/tlo.10265. Epub 2011 Jun 1.
- Derived from this study: PubMed 33325055Diaz GA, Schulze A, McNutt MC, Leao-Teles E, Merritt JL 2nd, Enns GM, Batzios S, Bannick A, Zori RT, Sloan LS, Potts SL, Bubb G, Quinn AG. Clinical effect and safety profile of pegzilarginase in patients with arginase 1 deficiency. J Inherit Metab Dis. 2021 Jul;44(4):847-856. doi: 10.1002/jimd.12343. Epub 2021 Jan 26.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Josie Gayton study director
Aeglea Biotherapeutics, Inc.
9 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AEB1102 in people with Arginase I Deficiency and Hyperargininemia, run by Aeglea Biotherapeutics at 9 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Canada, Portugal, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subjects with adverse events (time frame: weekly throughout the study, up to 14 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02488044, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2019.