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

Study Overview
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Brief Summary
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Study ABX1100-1001 is a first-in-human (FIH), phase 1 study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of a single ascending dose (SAD) and multiple doses (MD) of ABX1100 administered intravenously to healthy participants. Part A is a SAD, double-blind, placebo-controlled, randomized design in normal healthy volunteers. Part A will enroll up to 24 subjects (18 active: 6 placebo). Part B is a MD, double-blind, placebo-controlled, randomized design in normal healthy volunteers. Part B will commence after Part A and enroll 12 subjects (9 active: 3 placebo).

Official Title
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A Phase 1, Single Ascending Dose and Multiple Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ABX1100 in Normal Healthy Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Drug: ABX1100 injection for IV infusion
* Drug: Placebo injection for IV infusion


Participation Criteria
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Eligibility Criteria
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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. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A Single Dose (active)<br>Subjects will receive 1 single IV dose of ABX1100 on Day 1. | Drug: ABX1100 injection for IV infusion<br>* Centyrin protein-siRNA conjugate<br>|
| Placebo Comparator: Part A Single Dose (placebo)<br>Subjects will receive 1 single IV dose of placebo on Day 1. | Drug: Placebo injection for IV infusion<br>* placebo saline injection<br>|
| Experimental: Part B Multi-dose (active)<br>Subjects will receive 1 IV dose of ABX1100 on Day 1 and Day 29 each. | Drug: ABX1100 injection for IV infusion<br>* Centyrin protein-siRNA conjugate<br>|
| Placebo Comparator: Part B Multi-dose (placebo)<br>Subjects will receive 1 IV dose of placebo on Day 1 and Day 29 each. | Drug: Placebo injection for IV infusion<br>* placebo saline injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with treatment-emergent adverse events (TEAEs) | Adverse Events will be graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Adverse events (AEs) will be reported based on clinical laboratory tests, vital signs, physical examinations, electrocardiograms, and echocardiograms from the time informed consent is signed through 8 weeks after ABX1100 administration for Part A and through 12 weeks after ABX1100 administration for Part B. AEs will be considered to be treatment emergent (TEAE) if they occurred or worsened in severity after the first dose of study treatment. | up to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma pharmacokinetics as measured by Cmax | Plasma samples will be taken pre-dose, 10 min, end of infusion, 0.5, 1, 3, 6, 9, 12 and 24 hours after the start of ABX1100 administration | 0-24 hours after ABX1100 administration | 
| Plasma pharmacokinetics as measured by Tmax | Plasma samples will be taken pre-dose, 10 min, end of infusion, 0.5, 1, 3, 6, 9, 12 and 24 hours after the start of ABX1100 administration | 0-24 hours after ABX1100 administration | 
| Plasma pharmacokinetics as measured by AUC | Plasma samples will be taken pre-dose, 10 min, end of infusion, 0.5, 1, 3, 6, 9, 12 and 24 hours after the start of ABX1100 administration | 0-24 hours after ABX1100 administration | 
| Immunogenicity of AXB1100 as measured by anti-ABX1100 antibodies in serum | Plasma samples will be taken pre-dose, Day 15 and Day 29 after ABX1100 administration (Part A); Plasma samples will be taken pre-dose, Day 15, Day 29 Day 43 and Day 57 after ABX1100 administration (Part B) | Up to 8 weeks |