Assessing the safety and effects of ABX1100 in healthy individuals and patients with Late-Onset Pompe Disease

A Phase 1a/1b, Single Ascending Dose and Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ABX1100 in Normal Healthy Volunteers and Late-onset Pompe Disease Patients

This study is testing a new treatment called ABX1100 to see if it's safe and effective for healthy people and those with Late-Onset Pompe Disease.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 46 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Aro Biotherapeutics (Industry-sponsored)
• Locations: 3 sites (Fairfax, Virginia and 2 other locations)
• Trial ID: NCT06109948 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, tolerability, pharmacokinetics, and pharmacodynamics of ABX1100 through a series of doses administered intravenously. It consists of three parts: Part A involves a single ascending dose in healthy volunteers, Part B assesses multiple doses in healthy volunteers, and Part C focuses on multiple doses in patients with Late-Onset Pompe Disease. The study employs a double-blind, placebo-controlled design to ensure reliable results and includes a review process to monitor safety and efficacy throughout the phases.

Who should consider this trial

Good fit: Ideal candidates include individuals with Late-Onset Pompe Disease who meet specific eligibility criteria.

Not a fit: Patients with conditions that prevent them from participating in the study, such as those with a BMI outside the specified range or those who cannot undergo muscle biopsies, may not benefit.

Why it matters

Potential benefit: If successful, this study could lead to a new treatment option for patients with Late-Onset Pompe Disease.

How similar studies have performed: While this approach is novel in the context of ABX1100, similar studies assessing safety and efficacy of new treatments in rare diseases have shown promise.

Eligibility criteria

Parts A-B Inclusion Criteria:

* Body mass index (BMI) between 18.0 and 32.0 kg/m2, inclusive and weight between 50 and 90 kg, inclusive.
* Agree not to have a tattoo or body piercing until the end of the study.
* Agree not to receive COVID-19 vaccination from 7 days prior to first study drug administration until at least 7 days after the last study drug administration.
* Agree not to receive a vaccination (live attenuated vaccine) during the study and until 60 days after the study has ended (last study procedure).
* Willing to undergo needle muscle biopsies.
* Willing to avoid strenuous activities 48 hours before needle muscle biopsy and throughout the study.
* Female participants who are sexually active with a non-sterilized partner must be non-pregnant and non-lactating and agree to use a highly effective method of contraception.
* Males of childbearing potential must agree to use a highly effective method of contraception with female sexual partners of childbearing potential and not donate sperm during study participation and for 90 days after last administration of study drug ABX1100 or placebo.

Parts A-B Exclusion Criteria:

* Known history or presence of any clinically significant hepatic, renal/genitourinary, gastrointestinal, cardiovascular, cerebrovascular, pulmonary, endocrine, immunological, musculoskeletal, neurological, psychiatric, dermatological or hematological disease or condition.
* History of any inherited or acquired skeletal muscle diseases (for example, Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD), Limb-Girdle Muscular Dystrophy (LGMD), Myotonic Dystrophy, Spinal Muscular Atrophy (SMA), Polymyositis, Rhabdomyolysis and Inclusion Body Myositis (IBM).
* History of any inherited or acquired cardiac disease including congestive heart failure, ischemic heart disease, or arrhythmias; an abnormal ECG.
* History of cancer within past 5 years, with the exception of treated or excised skin basal cell carcinoma.
* Any clinically significant illness, medical/surgical procedure, or trauma within 4 weeks prior to the screening visit
* Presence of any significant physical or organ abnormality.
* Major surgery within 6 months prior to the start of the study.
* Current smoker, recent history of smoking and/or use of any nicotine-containing products (within past 6 months).
* A known history or positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody or human immunodeficiency virus (HIV) infection.
* Currently participating in another investigational trial or have received any investigational drug within the past 30 days.

Part C Key Inclusion criteria

* Male or female LOPD patients aged ≥ 18 years (inclusive) of age, at the time of informed consent.
* Body mass index (BMI) between 18.0 and 35.0 kg/m2, inclusive and weight \>50 kg.
* Agree not to receive COVID-19 vaccination from 7 days prior to first study drug administration until at least 7 days after the last study drug administration or after the final study procedure, whichever is later.
* Agree not to receive a vaccination (live attenuated vaccine) during the study and until 60 days after the study has ended (last study procedure).
* Willing to undergo needle muscle biopsies.
* Documented Acid alpha-glucosidase (GAA) deficiency and mutation analysis from blood, skin, or muscle tissue for confirmation of diagnosis of LOPD.
* Currently receiving a stable dose of standard of care enzyme replacement therapy (ERT) regularly for a minimum of 6 months immediately prior to study entry
* Capable of walking 50 meters with or without an assistive device.
* Predicted upright Forced Vital Capacity (FVC) \>= 30% within the past year prior to study entry, not requiring invasive mechanical ventilation. Non-invasive, temporary, respiratory support is acceptable
* Female participants who are sexually active with a non-sterilized partner must be non-pregnant and non-lactating and agree to use a highly effective method of contraception.
* Males of childbearing potential must agree to use a highly effective method of contraception with female sexual partners of childbearing potential and not donate sperm during study participation and for 90 days after last administration of study drug ABX1100.

Part C Key Exclusion criteria

* History of muscle biopsy within 1 month of Day 1 or planning to undergo non-study related muscle biopsies during study period.
* History of coronary artery disease or cardiovascular disease.
* History or presence of gastrointestinal, renal, or hepatic disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
* Presence of any significant physical or organ abnormality as determined by the PI/Sub-Investigator.
* Resting seated blood pressure \< 90/40 mmHg or \> 140/90 mmHg , unless deemed not clinically significant by the PI/Sub-Investigator.
* Resting seated heart rate \< 45 bpm or \> 99 bpm, unless deemed not clinically significant by the PI/Sub-Investigator.
* Intolerance to and/or difficulty with blood sampling through venipuncture.
* Positive pregnancy test for female participants.
* Currently participating in another investigational trial or have received any investigational drug within the past 30 days or 5 elimination half-lives of the investigational drug, whichever is longer, prior to dosing.
* Requires a wheelchair or invasive ventilation.
* Fridericia's corrected QT (QTcF) \> 450 ms for participants or history of QT interval prolongation unless deemed not clinically significant by the PI/Sub-Investigator.
* Uncontrolled diabetes (Hemoglobin A1c \[HbA1c\] equal to or higher than 7.5%).
* A known history or positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody or human immunodeficiency virus (HIV) infection.

Where this trial is running

Fairfax, Virginia and 2 other locations

• Lysosomal and Rare Disorders Research and Treatment Center, Inc — Fairfax, Virginia, United States (Recruiting)
• MAGIC clinic — Calgary, Alberta, Canada (Recruiting)
• McMaster University — Hamilton, Ontario, Canada (Not_yet_recruiting)

Study contacts

• Study coordinator: Aro Study Information Center

Conditions Healthy; Late Onset Pompe Disease