A Study of AT-02 in Subjects With Systemic Amyloidosis.

Study Overview
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Brief Summary
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This is a Phase 2 open-label extension study to evaluate the long-term safety, tolerability, and clinical activity of AT-02. AT-02 is an investigational medicinal product being developed to treat systemic amyloidosis.

Detailed Description
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The study will enroll subjects with systemic amyloidosis who have participated in AT02-001 study. The study includes screening period (56 days), treatment period (week 104), follow up (week 112). The total duration of participant in study is up to 120 weeks. A Safety Review Committee (SRC) will periodically convene and review all available clinical and laboratory data during the study. A single SRC will monitor safety across all AT-02 studies to ensure that safety signals are assessed in aggregate.

Official Title
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A Phase 2, Open-label Extension Study to Evaluate the Long-term Safety and Tolerability of AT-02

Conditions
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Amyloidosis; Systemic

Intervention / Treatment
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* Drug: AT02


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject understands the study procedures and can give signed informed consent. Subject is willing and able to comply with this protocol and will be available for the entire duration of the study. Subject must have a confirmed diagnosis of SA per the diagnostic criteria specified in the parent study protocol. Subject must have participated in the study AT01-001 and wishes to receive open-label AT-02. AT02-001 Part 2: a. Subjects must have completed the last follow-up visit in AT02-001 Part 2 without significant adverse events, as determined by the Investigator. AT02-001 Part 3: a. Subjects must have completed the post-treatment imaging studies in AT02-001Part 3 (e.g., CMR, echocardiogram) without significant AEs in the parent study as determined by the Investigator. Must continue to satisfy the eligibility criteria in the parent study protocol for WOCBP, WONCBP, or male participants Exclusion Criteria: Is pregnant, breastfeeding, or is planning to become pregnant or breastfeed during this study and follow-up period. Is mentally or legally incapacitated, has significant emotional problems at the time of the study, or has a history of psychosis. Has acquired any new, clinically significant underlying illness since enrollment in the parent study. Has any clinically significant worsening of organ function associated with underlying SA or clinically significant change in concomitant medications for the treatment of SA since enrollment in the parent study. Estimated glomerular filtration (eGFR) ≤30 mL/min/1.73 m2. Currently using any prohibited concomitant medications. Any contraindication to MRI or MRI contrast. Is currently participating in an interventional clinical study or has participated in another clinical study (other than AT02-001) within the last four (4) weeks or within five (5) half-lives of the prior study treatment, whichever is longer.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

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: A (AT-02)<br>Subjects will receive AT-02 via intravenous infusion once every two or 4 weeks for 104 weeks (52 total AT-02 administrations). | Drug: AT02<br>* Dosage Form: Solution for injection/infusion Dosage level: Different dose levels of AT02 Route of Administration: Intravenous use<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence, frequency, and severity of Treatment-emergent adverse events (TEAEs) as assessed National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version 5.0) |  | Up to 112 weeks | 
| To assess the safety and tolerability of AT-02 through change from baseline in clinical laboratory results |  | Up to 112 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess PK of AT-02 during long-term administration | Parameter: maximum observed concentration of AT-02 (Cmax) | Up to 112 weeks | 
| To assess PK of AT-02 during long-term administration | Parameter: time to maximum observed AT-02 concentration (Tmax) | Up to 112 weeks | 
| To assess PK of AT-02 during long-term administration | Parameter: AUClast | Up to 112 weeks | 
| To assess PK of AT-02 during long-term administration | Parameter: AUCinf | Up to 112 weeks | 
| To assess PK of AT-02 during long-term administration | Parameter: volume of distribution at steady state (Vss) | Up to 112 weeks | 
| To assess PK of AT-02 during long-term administration | Parameter: total body clearance (CL) of AT-02 | Up to 112 weeks | 
| To assess PK of AT-02 during long-term administration | Parameter: AT-02 half-life (t½) | Up to 112 weeks | 
| Incidence of treatment-emergent Anti-drug antibodies (ADAs) | The number and percentage of subjects who develop detectable ADA will be summarized by dose cohort. | Up to 112 weeks | 
| To evaluate the clinical efficacy of AT-02 during long-term administration through change from baseline in biomarkers | Biomarkers include serum N-terminal prohormone of brain natriuretic peptide (NT-proBNP) | Up to 112 weeks | 
| To evaluate the clinical efficacy of AT-02 during long-term administration through change from baseline in biomarkers | Biomarkers include serum High-sensitivity cardiac troponin T (hsTnT) | Up to 112 weeks | 
| To evaluate the clinical efficacy of AT-02 during long-term administration through change from baseline in biomarkers | Biomarkers include serum Urine albumin creatinine ratio (UACR) | Up to 112 weeks | 
| Serial cardiac magnetic resonance assessments of systemic amyloidosis |  | Up to 112 weeks |