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

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Hypercholesterolemia	Drug: ALN-PCSSC; Drug: Sterile Normal Saline (0.9% NaCl)	Phase 1

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	70 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Participant)
Primary Purpose:	Treatment
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 Start Date :	December 2014
Actual Primary Completion Date :	May 2015
Actual Study Completion Date :	November 2015

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: ALN-PCSSC	Drug: ALN-PCSSC; Single or multiple doses of ALN-PCSSC by subcutaneous (sc) injection
Placebo Comparator: Sterile Normal Saline (0.9% NaCl)	Drug: Sterile Normal Saline (0.9% NaCl); calculated volume to match active comparator

Outcome Measures

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Primary Outcome Measures :

1. 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 Measures :

1. 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 ]
2. 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 ]
3. 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 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 60 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

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)

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United Kingdom
Covance Clinical Research Unit
Leeds, United Kingdom
Richmond Pharmacology
London, United Kingdom

Sponsors and Collaborators

Alnylam Pharmaceuticals

The Medicines Company

Investigators

Study Director:	Robert Kauffman, MD	Alnylam Pharmaceuticals

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Responsible Party:	Alnylam Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT02314442 History of Changes
Other Study ID Numbers:	ALN-PCSSC-001
First Posted:	December 11, 2014
Last Update Posted:	December 17, 2015
Last Verified:	December 2015

Keywords provided by Alnylam Pharmaceuticals:

LDL-C; RNAi therapeutic

Additional relevant MeSH terms:

Hypercholesterolemia; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases