A Three-part, Phase 1, Single-ascending, and Multiple-ascending Dose Escalation Study in Healthy Volunteers and Subjects With Systemic Amyloidosis to Assess the Safety, Tolerability, and Pharmacokinetics of AT-02
Overview
- Phase
- Phase 1
- Intervention
- AT-02
- Conditions
- Amyloidosis; Systemic
- Sponsor
- Attralus, Inc.
- Enrollment
- 100
- Locations
- 11
- Primary Endpoint
- Incidence and frequency of abnormal and clinically significant abnormal clinical laboratory parameter values.
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a multicenter, international, three-part, Phase 1 study designed to evaluate the safety, tolerability, and PK of rising single doses of AT-02 in healthy volunteers and in subjects with systemic amyloidosis and to assess the safety, tolerability, and PK of multiple doses of AT-02 in subjects with systemic amyloidosis.
Detailed Description
Systemic amyloidosis is an incurable disease, and about 20% of patients with cardiac or advanced kidney involvement experience early deaths (\<1 year). Despite recent progress in proteasome inhibitors, chemotherapies, and immunotherapies that target plasma cells have greatly improved the prognosis of patients with systemic amyloidosis, median survival remains low at approximately five years. AT-02 (INN: not yet available) is a full-length, humanized, recombinant immunoglobulin 1 (IgG1)-like glycoprotein monoclonal antibody (mAb) that is being developed to treat systemic amyloidosis. This is a three-part, Phase 1 study designed to evaluate the safety, tolerability, and PK of rising single doses of AT-02 in healthy volunteers (HV) and in subjects with systemic amyloidosis (SA) and to assess the safety, tolerability, and PK of multiple doses of AT-02 in subjects with systemic amyloidosis. Part 1 is a double-blind, single-center, single-ascending dose escalation study in HV to assess the safety, tolerability, and PK of AT-02. Healthy volunteers between 18 to 56 years of will be enrolled in the Part 1 study. Part 2 is an open-label, single-ascending dose escalation study in subjects with systemic amyloidosis to assess the safety, tolerability, and PK of AT-02 and to identify a maximum tolerated dose (MTD). Subjects with SA over 18 years of age will be involved in the Part 2 study. Part 3 is an open-label, multiple-ascending dose, dose escalation study in subjects with systemic amyloidosis to assess the safety, tolerability, PK, PD, and clinical activity of multiple doses of AT-02. Subjects with SA ≥18 and ≤85 years of age will be involved in the Part 3 study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Eligibility Criteria for Healthy Volunteers:
- •Healthy volunteers are eligible to be included in the study only if all the following criteria apply:
- •Understands the study procedures and can give signed informed consent
- •Male or female between \>18 and \<56 years of age.
- •Willing and able to comply with this protocol and informed consent and be available for the entire duration of the study.
- •Willing to abstain from alcohol and strenuous physical activity (i.e., strenuous or unaccustomed weightlifting, running, bicycling, etc.) from 48 hours prior to study treatment administration until discharge from the clinical unit and prior to each outpatient visit.
- •In good general health, determined by no clinically significant findings in the opinion of the Investigator from medical history, physical examination, 12-lead electrocardiogram (ECG), clinical laboratory findings, and vital signs at Screening and Phase 1 unit Check-in.
- •Has body mass index (BMI) of 18 to 32 kg/m2, inclusive.
- •Women of childbearing potential (WOCBP)
- •WOCBP must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug.
Exclusion Criteria
- Not provided
Arms & Interventions
Part 1 AT-02
Part 1 enrolling Healthy Volunteers (Randomised, Double-blind) Drug: AT-02 Dosage: 30mg to 1000mg Dosage Form \& Route of Admin: Solution for IV Infusion
Intervention: AT-02
Part 1 Placebo
Part 1 enrolling Healthy Volunteers (Randomised, Double-blind) Dosage Form \& Route of Admin: Normal Saline Solution for IV Infusion
Intervention: AT-02 (Placebo)
Part 2 AT-02
Part 2 enrolling Systemic Amyloidosis Participants (Single-Arm, Open-label) Drug: AT-02 Dosage: 300mg to 4000mg Frequency: Single Dose Dosage Form \& Route of Admin: Solution for IV Infusion
Intervention: AT-02
Part 3 AT-02
Part 3 enrolling Systemic Amyloidosis Participants (Single-Arm, Open-label) Drug: AT-02 Dosage: Dose levels will be determined by the SRC. The starting dose in Part 3 will be determined by the SRC based on all available safety, tolerability, PK, and PD data from all prior cohorts Frequency: Multiple Doses Dosage Form \& Route of Admin: Solution for IV Infusion
Intervention: AT-02
Outcomes
Primary Outcomes
Incidence and frequency of abnormal and clinically significant abnormal clinical laboratory parameter values.
Time Frame: Up to 85+/-7 Days
Incidence of treatment-emergent anti-drug antibodies (ADA)
Time Frame: Up to 85+/-7 Days
The number and percentage of subjects who develop detectable ADA will be summarized by dose cohort.
Incidence of dose-limiting toxicities (DLTs) in subjects with systemic amyloidosis.
Time Frame: Up to 85+/-7 Days
A DLT is defined as any related TEAE with a National Cancer Institute (NCI) CTCAE version 5.0 Grade ≥3 which also represents a shift from Baseline clinical status of \>1 NCI CTCAE Grade.
Incidence and severity of treatment-emergent adverse events (TEAEs) from Day 1 to end of study (EOS).
Time Frame: Up to 57+/-7 days
Safety will be assessed by review of clinical laboratory parameters and incidence and severity of TEAEs (graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5).
Secondary Outcomes
- To determine the plasma pharmacokinetics (PK) profile of AT-02(Up to 85+/-7 Days)