ASC618 Gene Therapy in Hemophilia A Patients

Study Overview
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Brief Summary
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Currently, hemophilia A patients are managed with prophylactic or on-demand replacement therapy with recombinant FVIII or alternative therapeutics. The major challenges of current treatment regimens, such as the short half-life of hemophilia therapeutics with the need for frequent IV injections, encourage the current efforts for gene transfer therapy. This study will evaluate the safety and preliminary efficacy of ASC618, an AAV vector encoding B-domain deleted codon-optimized human factor VIII under a synthetic liver-directed promoter

Official Title
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Assessment of Safety and Preliminary Efficacy of ASC618 in Subjects With Severe and Moderately Severe Hemophilia A

Conditions
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Hemophilia A

Intervention / Treatment
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* Biological: ASC618


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male ≥18 years of age Severe or moderately severe hemophilia A (FVIII activity ≤ 2 IU/dL) as evidenced by medical history Received FVIII prophylactic or on-demand replacement therapy for ≥ 150 accumulated days (exposure days) ≥12 bleeding episodes if receiving on-demand therapy over the preceding 12 months BMI ≤ 30 Agree to use double-barrier contraceptive until at least 3 consecutive semen samples are negative after ASC-618 infusion Exclusion Criteria: Pre-existing immunity to AAV8 vector as defined by AAV8 total antibodies and neutralizing antibodies qualified tests. Current inhibitors, or history of high titer FVIII inhibitors Presence of > Grade 2 liver fibrosis on elastography/Fibroscan or comparable imaging methodology History of chronic renal disease Active infection or any immunosuppressive disorder History of cardiac surgery and need anticoagulant therapy Any cardiovascular / genetic risk factors for thromboembolic disorders Evidence of active Hepatitis B, Hepatitis C, Human Immunodeficiency Virus (HIV)-1/2 or syphilis infection. Receipt of any vector or gene transfer agent Current antiviral therapy for hepatitis B or C

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASC618<br>Experimental Arm | Biological: ASC618<br>* ASC618 will be given as a single IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse events, and serious AEs |  | 12 months post-infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in FVIII activity levels from baseline |  | 12 months post-infusion | 
| Annualized FVIII consumption |  | 12 months post-infusion | 
| Annualized bleeding rate (ABR) |  | 12 months post-infusion |