A First in Human Study of STT-5058, an Antibody That Binds ApoC3

Study Overview
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Brief Summary
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A First in Human Study of STT-5058, an Antibody That Binds ApoC3, investigating single and multiple ascending intravenous doses and ascending subcutaneous doses of STT-5058 in otherwise healthy volunteers with elevated triglyceride levels

Detailed Description
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The study is in five parts. Part A is up to 6 single ascending intravenous dose cohorts of STT-5058 in otherwise healthy volunteers with TRGs >150mg/dL. Part B is up to 4 multiple ascending intravenous dose cohorts of STT-5058 in otherwise healthy volunteers with TRGs >150mg/dL who will receive 3 doses at 2 week intervals. Part C will recruit a single cohort of patient volunteers with TRG >200mg/dL who will receive 3 doses at 2 week intervals of STT-5058. Part D will investigate up to 2 single ascending doses of subcutaneous STT-5058. Part E will recruit a single cohort of otherwise healthy volunteers with TRG > 150mg/dL to receive 4 doses subcutaneously of STT-5058 over 4 weeks

Official Title
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A Double-blind, Randomised, Placebo-controlled, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple-ascending Doses of Intravenously Administered STT-5058 in Otherwise Healthy Subjects With Elevated Triglyceride Levels and Single-ascending and Multiple Doses of Subcutaneously Administered STT-5058 in Otherwise Healthy Subjects With Elevated Triglyceride Levels and Patient Volunteers With Hypertriglyceridemia.

Conditions
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Hypertriglyceridemia

Intervention / Treatment
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* Drug: STT-5058
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: in good health Able to comprehend and willing to sign an ICF and to abide by the study restrictions. Females will not be pregnant or lactating, and females of childbearing potential and males will agree to use contraception Parts A, B and D BMI between 18 and 35 kg/m2 inclusive Fasting Triglycerides between 150 and 400mg/dL inclusive Part C Fasting Triglycerides between 200 and 400 mg/dL inclusive Fasting LDL-C between 70 and 160 mg/dL inclusive BMI between 18 and 40 kg/m2 Exclusion Criteria: significant history or clinical manifestation of metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator Confirmed (eg, 2 consecutive measurements) systolic blood pressure >150 or <90 mmHg, diastolic blood pressure >90 or <50 mmHg, and heart rate >90 or <40 beats per minute at Screening, Check-in, or prior to dosing on Day 1. History of alcoholism or drug/chemical abuse within 2 years prior to Check-in. Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days or 5 half-lives (if known), whichever is longer, prior to dosing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STT-5058<br> | Drug: STT-5058<br>* Monoclonal Antibody STT-5058<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching placebo to STT-5058<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability | incidence and severity of adverse events | 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC | Area under the PK curve | 10-14 weeks | 
| Cmax | Maximum concentration | 24 hours | 
| Half life | time to reduction in plasma levels by 50% | 10-14 weeks |