Clinical trial NCT03626662: Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Study of AMG 890 in Subjects With Elevated Plasma Lipoprotein(a)
Official title: A Phase 1, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 890 in Subjects With Elevated Plasma Lipoprotein(a)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cardiovascular Disease
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2018-08-13
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This is a first-in-human, randomized, double-blind, placebo-controlled, single ascending dose study in subjects with elevated plasma Lipoprotein(a) \[Lp(a)\]. AMG 890 will be evaluated in approximately 80 subjects to assess safety, tolerability, pharmacokinetics and pharmacodynamic effects.


Eligibility criteria: Inclusion Criteria:

* Men and women with ages between 18 and 70 years old, inclusive.
* Protocol-defined elevated plasma Lp(a) level.
* Body mass index (BMI) greater than or equal to 18 and less than or equal to 40 kg/m2, at screening.
* Women must be of non-reproductive potential.
* Other Inclusion criteria may apply

Exclusion Criteria:

* Currently receiving treatment in another investigational device or drug study.
* Women who are lactating/breastfeeding or who plan to breastfeed while on study or through 90 days after receiving the last dose of investigational product (for subjects who withdraw prior to end of study).
* History or evidence of a clinically significant disorder, condition or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
* History or clinical evidence of bleeding diathesis or any coagulation disorder.
* History or clinical evidence of peripheral neuropathy.
* Other Exclusion criteria may apply

Primary outcomes:
measure: Subject incidence of treatment-emergent adverse events
timeFrame: up to 365 days
measure: Changes in blood pressure
timeFrame: Up to 365 days
measure: Changes in heart rate
timeFrame: Up to 365 days
measure: Changes in respiratory rate
timeFrame: Up to 365 days
measure: Changes in temperature
timeFrame: Up to 365 days
measure: Changes in QRS interval
timeFrame: Up to 365 days
measure: Changes in PR interval
timeFrame: Up to 365 days
measure: Changes in QT interval
timeFrame: Up to 365 days
measure: Changes in RR interval
timeFrame: Up to 365 days
measure: Changes in red blood cells
timeFrame: Up to 365 days
measure: Changes in platelets
timeFrame: Up to 365 days
measure: Changes in white blood cells
timeFrame: Up to 365 days
measure: Changes in prothrombin time (PT)
timeFrame: Up to 365 days
measure: Changes in international normalized ratio (INR)
timeFrame: Up to 365 days
measure: Changes in activated partial thromboplastin time (aPTT)
timeFrame: Up to 365 days
measure: Changes in Thrombin time (TT)
timeFrame: Up to 365 days
measure: Changes in aspartate aminotransferase (AST) levels (units: U/L)
timeFrame: Up to 365 days
measure: Changes in alanine aminotransferase (ALT) levels (units: U/L)
timeFrame: Up to 365 days
measure: Changes in total bilirubin levels (units: μmol/L)
timeFrame: Up to 365 days
measure: Changes in direct bilirubin levels (units: μmol/L)
timeFrame: Up to 365 days
measure: Changes in alkaline phosphatase levels (units: U/L)
timeFrame: Up to 365 days
measure: Changes in total protein levels (units: g/L)
timeFrame: Up to 365 days
measure: Changes in albumin levels (units: g/L)
timeFrame: Up to 365 days
Secondary outcomes:
measure: Pharmacokinetics parameter of maximum observed concentration (Cmax)
timeFrame: up to 365 days
measure: Pharmacokinetics parameter of time of maximum observed concentration (tmax)
timeFrame: up to 365 days
measure: Pharmacokinetics parameter of area under the concentration time curve (AUC)
timeFrame: up to 365 days
measure: Change in plasma Lp(a) over time
timeFrame: Up to 365 days
measure: Percent change in plasma Lp(a) over time
timeFrame: Up to 365 days
Other outcomes:
Locations:
city: Tustin
country: United States
facility: Orange County Research Center
state: California
city: Boca Raton
country: United States
facility: Excel Medical Clinical Trials
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: South Miami
country: United States
facility: QPS Miami Research Associates
state: Florida
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: New York
country: United States
facility: New York University
state: New York
city: Cincinnati
country: United States
facility: Medpace Inc
state: Ohio
city: Adelaide
country: Australia
facility: Clinical Medical and Analytical eXellence CMAX
state: South Australia
city: Nedlands
country: Australia
facility: Linear Clinical Research Limited
state: Western Australia
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Koren MJ, Moriarty PM, Baum SJ, Neutel J, Hernandez-Illas M, Weintraub HS, Florio M, Kassahun H, Melquist S, Varrieur T, Haldar SM, Sohn W, Wang H, Elliott-Davey M, Rock BM, Pei T, Homann O, Hellawell J, Watts GF. Preclinical development and phase 1 trial of a novel siRNA targeting lipoprotein(a). Nat Med. 2022 Jan;28(1):96-103. doi: 10.1038/s41591-021-01634-w. Epub 2022 Jan 13.