Phase 1/2 Study of ABO-101 in Primary Hyperoxaluria Type 1

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Arbor Biotechnologies Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16], Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

3 Sep 2025 → ongoing

Decision date (initial)

2025-05-19

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Arbor Biotechnologies, Inc.

External identifiers

EU CT number

2024-518144-20-00

WHO UTN

U1111-1315-7113

ClinicalTrials.gov

NCT06839235

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Safety, Efficacy, Pharmacokinetic, Pharmacodynamic, Others

To evaluate the safety and tolerability of ABO-101 in participants with PH1

Secondary objectives 3

1. To evaluate the pharmacodynamics of ABO- 101 in participants with PH1
2. To characterize the pharmacokinetics of ABO-101 in participants with PH1
3. To characterize the immunogenicity to ABO-101 in participants with PH1

Conditions and MedDRA coding

Primary Hyperoxaluria Type 1 (PH1)

Study design 2 periods

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut, Food And Drug Administration, Medicines And Healthcare Products Regulatory Agency

Plan to share IPD

Yes

IPD plan description

Arbor Biotechnologies intends to share individual participant data (IPD) upon reasonable request from qualified researchers. Upon review of the proposed research and confirmation of researcher credentials Arbor and researcher will enter into a data sharing agreement. The agreement will govern the IPD access and include details of intended research, confirmation of adherence to privacy regulations and restrictions on the IPD processing. Transfer of the IPD will be in accordance with data protection laws. IPD will be provided in pseudonymized form. Researchers will be committed to secrecy, undertaking not to attempt reidentification of the IPD. IPD will be securely transferred and processed on systems in compliance regulatory security requirements. IPD availability periods will be determined during the course of the trial and specific details regarding data availability, access and processing protocols, and contact information to be outlined in the respective data sharing agreement.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 1. Confirmed diagnosis of PH1
2. 12. Weight ≤90 kg
3. 13. For female participants: a. If of childbearing potential, must agree to use at least 1 highly effective method of contraception from the time of signing the ICF through 12 months after dosing with ABO-101; b. Be postmenopausal c. Be surgically sterile at least 1 month prior to Screening
4. 14. For male participants: Must agree to use condoms with spermicide or abstain from sexual intercourse, and their female partners of childbearing potential must use a highly effective method of contraception from the time of signing the ICF through 4 months after dosing with ABO-101. Male participants must agree to not donate sperm through 4 months after trial drug administration
5. 15. Capable of providing signed informed consent. In case of participants who are below the legal age, informed consent must be obtained from the participant’s parent/LAR and the participant must provide assent per local and national requirements
6. 16. Must be willing to comply with the requirements of the trial
7. 2. Age at time of signing the ICF/assent form: a. Cohorts 1-3: ≥18 years to ≤64 years b. Cohort 4: ≥6 years to <18 years
8. 3. Documentation of PH1 as determined by genetic analysis confirming pathogenic mutations in the alanine-glyoxylate aminotransferase gene (AGXT)
9. 5. Mean of (CCI) valid 24-hour UOx ≥0.7 mmol (63 mg)/24 hours/1.73 m2
10. 6. Able to follow directions and provide 24-hour urine collections
11. 7. If taking pyridoxine (vitamin B6) for the treatment of PH1, must have been on a stable regimen for at least 90 days prior to ABO-101 administration, and be willing to remain on this stable regimen during Study Period 1
12. 8. Must meet the following laboratory: a. Within laboratory reference range or deemed clinically non-significant by the Investigator: AST, ALT, and total bilirubin b. eGFR ≥30 mL/min/1.73m2 based on CKD-EPI 2021 equation for participants ≥18 years of age at Screening and the Schwartz equation for participants <18 years of age at Screening c. Platelet count >100,000/mm3 d. Within laboratory reference range or deemed clinically non-significant by the Investigator: PT, aPTT, INR, D-dimer, and fibrinogen
13. 10. Participant must not have received any experimental agent for the treatment of PH1 for at least (CCI) half-lives
14. 11. Participant must agree to not participate in another interventional trial during the Screening Period and for at least 6 months following ABO-101 administration
15. 4. History of renal stone events, clinically related symptoms, or history of nephrocalcinosis.
16. 9. All available standard of care options (including approved siRNA treatment) were considered according to local medical practice and guidelines

Exclusion criteria 18

1. 1. Confirmed diagnosis of PH2 or PH3
2. 4. Participant has previously used (within past (CCI) months) or is currently on an approved or investigational urinary oxalate lowering (CCI) or (CCI) therapy
3. 5. Medical history includes clinical evidence of extrarenal systemic oxalosis, as determined by the Investigator
4. 6. Known hypersensitivity to any LNP component or history of Grade 3 or higher AE following administration of any LNP requiring treatment or discontinuation of treatment, or any LNP treatment-related AE that, in the opinion of the Investigator, may pose undue risk to the participant
5. 7. History of liver cirrhosis
6. 8. Known or suspected systemic bacterial, viral, or fungal infection, or requirement of systemic anti-infectives either ongoing or within 14 days prior to trial drug administration, or where inclusion in the clinical trial would jeopardize the participant’s health and wellbeing, as determined by the Investigator.
7. 10. History of active malignancy within 5 years prior to Screening except for adequately treated basal or squamous cell carcinoma of the skin, adequately treated cervical carcinoma in situ or adequately treated organ confined prostate cancer
8. 14. Use of antiplatelet (e.g., aspirin, clopidogrel) or antithrombotic therapy (e.g., warfarin, dabigatran, apixaban) within 14 days prior to ABO-101 administration.
9. 15. History of thrombotic disorders or medical history suggestive of predisposing factors for thromboembolic events (e.g., recent surgery or trauma, or known genetic disorder that increase the propensity for venous thromboembolism).
10. 11. Female participants who are pregnant or breastfeeding (or are planning either during the first 12 months)
11. 12. History of alcohol or drug abuse within 3 years prior to Screening
12. 13. History of active hepatitis B, C or human immunodeficiency virus (HIV) infection; or positive hepatitis B surface antigen. Participants who are hepatitis C virus (HCV) antibody positive must have negative HCV RNA
13. 16. Any condition or laboratory abnormality that in the opinion of the Investigator could pose undue risk, confound the ability to interpret trial results, or preclude compliance with the trial
14. 17. Anticipated survival <2 years in the opinion of the Investigator
15. 18. Unwilling to comply with trial procedures including Long-Term Safety Follow-Up
16. 2. History of a liver, kidney, or combined liver/kidney transplant
17. 3. Currently on dialysis or anticipated requirement for dialysis within the initial (CCI) months of the trial
18. 9. History of known gram-negative urinary tract infection or presumptively treated urinary tract infection (i.e., no culture) or gram-negative systemic infection within 90 days prior to ABO-101 administration

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence and severity of treatment-emergent adverse events (TEAEs), including ABO-101- related TEAEs and serious adverse events (SAEs)

Secondary endpoints 7

1. Percent change in 24-hour urinary oxalate excretion (UOx) from Baseline to Month (CCI)
2. Absolute change in UOx corrected for body surface area
3. Percent change in plasma glycolate from Baseline to Month (CCI)
4. Changes in estimated glomerular filtration rate (eGFR) from Baseline to Month (CCI) and Month (CCI)
5. Plasma concentrations for (CCI), and (CCI)
6. Urine concentrations for (CCI) and (CCI)
7. Antidrug antibodies to ABO-101 and anti-Cas12i2 protein antibodies

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Arbor Biotechnologies Inc.

Sponsor organisation

Arbor Biotechnologies Inc.

Address

20 Acorn Park Drive Suite 500

City

Cambridge

Postcode

02140-2133

Country

United States

Scientific contact point

Organisation

Arbor Biotechnologies Inc.

Contact name

Tara Naylor

Public contact point

Organisation

Arbor Biotechnologies Inc.

Contact name

Jennifer Casagrande

Third parties 14

Locations

3 EU/EEA countries · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 65 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications