Clinical trial NCT02314442: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypercholesterolemia
Keywords: LDL-C
RNAi therapeutic
Lead sponsor: Alnylam Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: The Medicines Company
First posted: 2014-12-11
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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)

Primary outcomes:
measure: 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
timeFrame: Part 1 (SAD phase): up to 180 days post dose; Part 2 (MD) phase: up to 180 days post final dose
Secondary outcomes:
measure: The pharmacokinetics (PK) of ALN-PCSSC (Cmax, tmax, AUC, t1/2)
timeFrame: 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
measure: The effect of ALN-PCSSC on serum levels of LDL-C
timeFrame: Through the sooner of final follow up visit or 180 days post final dose
measure: The effect of ALN-PCSSC on plasma levels of PCSK9
timeFrame: Through the sooner of final follow up visit or 180 days post final dose
Other outcomes:
Locations:
city: Leeds
country: United Kingdom
facility: Covance Clinical Research Unit
city: London
country: United Kingdom
facility: Richmond Pharmacology
Study officials:
affiliation: Alnylam Pharmaceuticals
name: Robert Kauffman, MD
role: STUDY_DIRECTOR
References:
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.