Multiple-Dose Safety Study Of RN316 For TheTreatment Of Hypercholesterolemia

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the safety and tolerability of repeated doses of RN316 in eligible healthy volunteers. RN316 is an investigational drug that is currently being studied as a cholesterol lowering therapy.

Official Title
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A Phase 1, Placebo-Controlled, Randomized Study To Assess The Safety, Tolerability, Pharmacokinetics, And Pharmacodynamics Following Multiple Intravenous Doses Of RN316 In Healthy Adult Subjects With Hypercholesterolemia

Conditions
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Hypercholesterolemia, Dyslipidemia

Intervention / Treatment
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* Biological: Placebo
* Biological: 1 mg/kg every 2 weeks
* Biological: 2 mg/kg every 4 weeks
* Biological: 4 mg/kg every 4 weeks
* Biological: 4 mg/kg every 8 weeks
* Biological: 8 mg/kg every 8 weeks
* Biological: 12 mg/kg every 8 weeks


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: LDL-C must be greater or equal to 130 mg/dl BMI must be between 18.5 and 40 kg/m2 Exclusion Criteria: History of cardiovascular or cerebrovascular event during the past year. Poorly controlled type 1 or type 2 diabetes mellitus Subjects who have taken lipid lowering therapies within the last 3 months of screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* Subjects will receive placebo or active treatment every 2 weeks for a total of 9 doses. Duration of IV infusion is 60 minutes. Total dose is based on subjects weight.<br>|
| Experimental: RN316: 1 mg/kg every 2 weeks<br> | Biological: 1 mg/kg every 2 weeks<br>* Subjects will receive placebo or active treatment every 2 weeks for a total of 9 doses. Duration of IV infusion is 60 minutes. Total dose is based on subjects weight.<br>|
| Experimental: RN316: 2 mg/kg every 4 weeks<br> | Biological: 2 mg/kg every 4 weeks<br>* Subjects will receive placebo or active treatment every 2 weeks for a total of 9 doses. Duration of IV infusion is 60 minutes. Total dose is based on subjects weight.<br>|
| Experimental: RN316: 4 mg/kg every 4 weeks<br> | Biological: 4 mg/kg every 4 weeks<br>* Subjects will receive placebo or active treatment every 2 weeks for a total of 9 doses. Duration of IV infusion is 60 minutes. Total dose is based on subjects weight.<br>|
| Experimental: RN316: 4 mg/kg every 8 weeks<br> | Biological: 4 mg/kg every 8 weeks<br>* Subjects will receive placebo or active treatment every 2 weeks for a total of 9 doses. Duration of IV infusion is 60 minutes. Total dose is based on subjects weight.<br>|
| Experimental: RN316: 8 mg/kg every 8 weeks<br> | Biological: 8 mg/kg every 8 weeks<br>* Subjects will receive placebo or active treatment every 2 weeks for a total of 9 doses. Duration of IV infusion is 60 minutes. Total dose is based on subjects weight.<br>|
| Experimental: RN316: 12 mg/kg every 8 weeks<br> | Biological: 12 mg/kg every 8 weeks<br>* Subjects will receive placebo or active treatment every 2 weeks for a total of 9 doses. Duration of IV infusion is 60 minutes. Total dose is based on subjects weight.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of dose limiting or intolerable treatment related adverse events (AEs). |  | Every Scheduled Visit | 
| Incidence, severity and causal relationship of treatment emergent AEs (TEAEs). |  | Every Scheduled Visit | 
| Incidence of abnormal and clinically relevant safety laboratories. |  | Screening and Days 29, 57, 85, 113, 135, 141, 169 and 197 | 
| Abnormal and clinically relevant changes in vital signs, BP, and ECG parameters. |  | Every Scheduled Visit | 
| Incidence of anti-drug-antibodies. |  | Baseline and Day 15 and monthly thereafter | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK parameter estimates including but not be limited to: AUC, Tmax, Cmax terminal elimination half life (t1/2), Clearance (CL), volume of distribution at steady state (Vss), and accumulation ratio (R) of RN316. |  | Day 1 and every scheduled visit thereafter | 
| Absolute and percentage change in LDL C from baseline. |  | Every scheduled visit except Day 1 | 
| Proportion of subjects who achieve a target LDL C of <100 mg/mL. |  | Every scheduled visit except Day 1 | 
| Proportion of subjects who achieve a target LDL C of <70 mg/dL. |  | Every scheduled visit except Day 1 | 
| Proportion of subjects achieving 50% decrease in LDL C from baseline. |  | Every scheduled visit except Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypercholesterolemia, Dyslipidemia, LDL, Cholesterol, High Cholesterol