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A Phase 1 Study of an Investigational Drug, ALN-PCSSC, in Subjects With Elevated Low Density Lipoprotein Cholesterol (LDL-C)

Primary Purpose

Hypercholesterolemia

Status

Completed

Phase

Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

ALN-PCSSC

Sterile Normal Saline (0.9% NaCl)

About this trial

This is an interventional treatment trial for Hypercholesterolemia focused on measuring LDL-C, RNAi therapeutic

Eligibility Criteria

18 Years - 60 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

Adequate complete blood counts, liver and renal function
Female subjects must be of non-childbearing potential; e.g. post-menopausal or pre-menopausal with surgical sterilization
Male subjects agree to use appropriate contraception
Willing to provide written informed consent and willing to comply with study requirements.
Non-smokers and non-nicotine users for at least 90 days before screening
On stable statin co-medication [for designated multiple dose cohorts only]

Exclusion Criteria:

Any uncontrolled or serious disease, or any medical or surgical condition, that may interfere with participation in the clinical study and/or put the subject at significant risk
Received an investigational agent within 90 days before the first dose of study drug or are in follow-up of another clinical study
History of multiple drug allergies or intolerance to subcutaneous injection
Received any medication or nutraceutical to alter serum lipids within 30 days before screening (non-statin cohorts only)

Sites / Locations

Covance Clinical Research Unit
Richmond Pharmacology

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

ALN-PCSSC

Sterile Normal Saline (0.9% NaCl)

Arm Description

Outcomes

Primary Outcome Measures

The safety of ALN-PCSSC evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation

Secondary Outcome Measures

The pharmacokinetics (PK) of ALN-PCSSC (Cmax, tmax, AUC, t1/2)

The effect of ALN-PCSSC on serum levels of LDL-C

The effect of ALN-PCSSC on plasma levels of PCSK9

Full Information

NCT ID

NCT02314442

First Posted

December 5, 2014

Last Updated

December 16, 2015

Sponsor

Alnylam Pharmaceuticals

Collaborators

The Medicines Company

1. Study Identification

Unique Protocol Identification Number

NCT02314442

Brief Title

A Phase 1 Study of an Investigational Drug, ALN-PCSSC, in Subjects With Elevated Low Density Lipoprotein Cholesterol (LDL-C)

Official Title

A Phase 1, Randomized, Single Blind, Placebo Controlled, Single Ascending Dose and Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered ALN PCSSC in Subjects With Elevated Low Density Lipoprotein Cholesterol

Study Type

Interventional

2. Study Status

Record Verification Date

December 2015

Overall Recruitment Status

Completed

Study Start Date

December 2014 (undefined)

Primary Completion Date

May 2015 (Actual)

Study Completion Date

November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Alnylam Pharmaceuticals

Collaborators

The Medicines Company

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ALN-PCSSC in subjects with elevated LDL-C.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hypercholesterolemia

Keywords

LDL-C, RNAi therapeutic

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

Participant

Allocation

Randomized

Enrollment

70 (Actual)

8. Arms, Groups, and Interventions

Arm Title

ALN-PCSSC

Arm Type

Active Comparator

Arm Title

Sterile Normal Saline (0.9% NaCl)

Arm Type

Placebo Comparator

Intervention Type

Drug

Intervention Name(s)

ALN-PCSSC

Intervention Description

Single or multiple doses of ALN-PCSSC by subcutaneous (sc) injection

Intervention Type

Drug

Intervention Name(s)

Sterile Normal Saline (0.9% NaCl)

Intervention Description

calculated volume to match active comparator

Primary Outcome Measure Information:

Title

The safety of ALN-PCSSC evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), and AEs leading to study drug discontinuation

Time Frame

Part 1 (SAD phase): up to 180 days post dose; Part 2 (MD) phase: up to 180 days post final dose

Secondary Outcome Measure Information:

Title

The pharmacokinetics (PK) of ALN-PCSSC (Cmax, tmax, AUC, t1/2)

Time Frame

Part 1 (SAD) phase: predose, 0.5,1,2,4,6,8,12,24,48,72,96 hours; 7, 14, 21, 28, 42, 56 days post-dose; Part 2 (MD) phase: predose, 0.5,1,2,4,6,8,12,24,48,72,96 hours; 7, 14, 21, 28, 29, 35, 42, 56, 84 days post-dose

Title

The effect of ALN-PCSSC on serum levels of LDL-C

Time Frame

Through the sooner of final follow up visit or 180 days post final dose

Title

The effect of ALN-PCSSC on plasma levels of PCSK9

Time Frame

Through the sooner of final follow up visit or 180 days post final dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Adequate complete blood counts, liver and renal function Female subjects must be of non-childbearing potential; e.g. post-menopausal or pre-menopausal with surgical sterilization Male subjects agree to use appropriate contraception Willing to provide written informed consent and willing to comply with study requirements. Non-smokers and non-nicotine users for at least 90 days before screening On stable statin co-medication [for designated multiple dose cohorts only] Exclusion Criteria: Any uncontrolled or serious disease, or any medical or surgical condition, that may interfere with participation in the clinical study and/or put the subject at significant risk Received an investigational agent within 90 days before the first dose of study drug or are in follow-up of another clinical study History of multiple drug allergies or intolerance to subcutaneous injection Received any medication or nutraceutical to alter serum lipids within 30 days before screening (non-statin cohorts only)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Robert Kauffman, MD

Organizational Affiliation

Alnylam Pharmaceuticals

Official's Role

Study Director

Facility Information:

Facility Name

Covance Clinical Research Unit

City

Leeds

Country

United Kingdom

Facility Name

Richmond Pharmacology

City

London

Country

United Kingdom

12. IPD Sharing Statement

Citations:

PubMed Identifier

27959715

Citation

Fitzgerald K, White S, Borodovsky A, Bettencourt BR, Strahs A, Clausen V, Wijngaard P, Horton JD, Taubel J, Brooks A, Fernando C, Kauffman RS, Kallend D, Vaishnaw A, Simon A. A Highly Durable RNAi Therapeutic Inhibitor of PCSK9. N Engl J Med. 2017 Jan 5;376(1):41-51. doi: 10.1056/NEJMoa1609243. Epub 2016 Nov 13.

Results Reference

derived

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A Phase 1 Study of an Investigational Drug, ALN-PCSSC, in Subjects With Elevated Low Density Lipoprotein Cholesterol (LDL-C)

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