A Phase 2 Long Term Safety Study of AEB1102 (CAEB1102-102A)
Research type
Research Study
Full title
An Open-label, Multicenter Study to Evaluate the Long-Term Safety, Tolerability, and Efficacy of AEB1102 in Patients with Arginase I Deficiency
IRAS ID
252576
Contact name
Spyros Batzios, Dr
Contact email
Sponsor organisation
Aeglea BioTherapeutics, Inc.
Eudract number
2018-003163-67
Clinicaltrials.gov Identifier
Clinicaltrials.gov Identifier
127774, IND Number
Duration of Study in the UK
3 years, 0 months, 0 days
Research summary
Research Summary
The study sponsor, Aeglea BioTherapeutics, Inc., is developing AEB1102 (pegzilarginase) a recombinant human arginase enzyme to treat excess arginase levels in patients with Arginase 1 Deficiency, a urea cycle disorder caused by a mutation in the arginase 1 gene that results in the inability to degrade the amino acid arginine. Arginase 1 Deficiency is a debilitating, progressive disease with significant morbidity and early mortality.
Pegzilarginase is an engineered human arginase 1 enzyme and is intended for use as enzyme replacement therapy to reduce the elevated blood arginine levels to the normal physiological range.
This Phase 2 clinical study is being conducted to evaluate the long-term safety, tolerability and efficacy of iv or sc administration of AEB1102 for the treatment of patients with Arginase I Deficiency and hyperargininaemia.
The study will enrol approximately 10 patients, adult and paediatric, with Arginase 1 Deficiency in the United States, Canada, Portugal, and UK.
Summary of Results
The study was conducted from December 2017 to December 2022 in the United States, Canada, Portugal, and the United Kingdom.
A total of 14 patients with Arginase 1 deficiency (ARG1-D) who had already been treated with pegzilarginase in a previous Phase 1/2 study (CAEB1102-101A) continued to receive the drug for up to 5 years. The predominantly female participants (11 versus 3 male participants) were aged between 6 and 32 years with minor limitations of gross motor skills at the start of the study. 3 participants (21%) had more severe limitations in their gross motor skills. 10 participants (71%) had mild to severe spasticity.
Participants continued with the same dose and schedule of pegzilarginase as they had at the end of the CAEB1102-101A study. However, doctors could adjust the dose based on how the drug was working in the body or if there were any safety concerns. The first 24 doses were given weekly by IV (into-the-vene). Thereafter, participants received weekly SC (under-the-skin) injections, starting with the same dose as the last IV treatment. 1 participant left the study early and stopped long-term treatment for personal reasons.
During the study, 7 participants (50%) had 1 or more health problems that the doctors thought were caused by the study drug (side effects). Common side effects (that were experienced in more than 2 participants) were high ammonia levels (in 4 participants, 36%) and vomiting (in 3 participants, 21%). All side effects were mild or moderate in intensity and mostly resolved during the study. For 2 participants, the high ammonia levels were serious, meaning that they had to be admitted to the hospital or stay there longer than expected. No side effects led to leaving the study, stopping the treatment, or death.
No participants developed antibodies against pegzilarginase during treatment, whether it was given by IV or SC. This means the body did not react negatively to the drug in a way that could affect how it works.
Overall, long-term use of pegzilarginase up to 5 years was well tolerated. All side effects were temporary, manageable, and either went away on their own or with routine medical care.
Over time, pegzilarginase helped keeping arginine levels in the blood within a healthy range. It also lowered levels of another connected substance, called guanidino compounds, increased levels of ornithine (a helpful amino acid), and led to improvements in movement and physical abilities (walking and balance ability, gross motor skills, spasticity) which are noticeable to the doctor and patient.
Where further information is available
To learn more about this study, you can find more detailed information on this website (EU database of clinical studies): https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fwww.clinicaltrialsregister.eu%252Fctr-search%252Fsearch%253Fquery%253D2018-003163-67.%2FNBTI%2FAyfBAQ%2FAQ%2F8f65dbd1-d77d-46d6-b34c-53282aa03bfc%2F1%2FoeK-whTszH&data=05%7C02%7Cedgbaston.rec%40hra.nhs.uk%7Cbe54164aef954a753a4608de1b8a56f7%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638978478142386443%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=VnvSN9uGgY86o9rdw8akzDxZgraZS62D%2BG7jZVdH%2BIk%3D&reserved=0
You can also find more details about this study at (US database of clinical studies): https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fclinicaltrials.gov%252Fstudy%252FNCT03378531.%2FNBTI%2FAyfBAQ%2FAQ%2F8f65dbd1-d77d-46d6-b34c-53282aa03bfc%2F2%2FB3sbU0nJkk&data=05%7C02%7Cedgbaston.rec%40hra.nhs.uk%7Cbe54164aef954a753a4608de1b8a56f7%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638978478142434984%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=fQDRBtZ49j4goLX0MveUFoXY2akUyCwS3X317K4eSOU%3D&reserved=0
The study results were also published in scientific journals: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fpubmed.ncbi.nlm.nih.gov%252F33325055%252F%252C%2FNBTI%2FAyfBAQ%2FAQ%2F8f65dbd1-d77d-46d6-b34c-53282aa03bfc%2F3%2FHH98KD9n1N&data=05%7C02%7Cedgbaston.rec%40hra.nhs.uk%7Cbe54164aef954a753a4608de1b8a56f7%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638978478142475466%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=ME0Ch3EnMy%2F0cPzVD9aCnF7Chnmx7XjoOuhjEUZf75I%3D&reserved=0 https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Ftrack.pstmrk.it%2F3ts%2Fpubmed.ncbi.nlm.nih.gov%252F40714964%252F.%2FNBTI%2FAyfBAQ%2FAQ%2F8f65dbd1-d77d-46d6-b34c-53282aa03bfc%2F4%2FRV1byxRk7K&data=05%7C02%7Cedgbaston.rec%40hra.nhs.uk%7Cbe54164aef954a753a4608de1b8a56f7%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638978478142512856%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=zYj9IYXViaYRugCZOFDIDIxolvNIJDSUOuT7l8hVvAc%3D&reserved=0REC name
West Midlands - Edgbaston Research Ethics Committee
REC reference
18/WM/0353
Date of REC Opinion
15 Jan 2019
REC opinion
Further Information Favourable Opinion