Study to Assess the Safety, Tolerability, PK and PD of ABX1100

Launched by ARO BIOTHERAPEUTICS · Oct 25, 2023

Keywords

ClinConnect Summary

This clinical trial, called ABX1100-1001, is looking at a new treatment called ABX1100 to see how safe it is and how it works in the body. The study will first test the drug on healthy volunteers in different groups to find the right dose and monitor any side effects. Once that part is complete, they will move on to testing the drug in patients with Late-Onset Pompe Disease, a rare muscle condition. The goal is to determine if this treatment can help improve their health.

To participate, individuals must be healthy volunteers aged 18-75, with a specific body weight and BMI. For patients with Late-Onset Pompe Disease, they should be at least 18 years old, confirm their condition through specific tests, and have been on stable enzyme replacement therapy or be treatment-naïve. Participants should be ready for some medical procedures, like blood tests and muscle biopsies, and will be asked to avoid certain activities and vaccinations during the study. This trial is a great opportunity to contribute to research that could benefit those with Pompe Disease, and participants will receive close monitoring throughout the study.

Gender

ALL

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.