Trial Evaluating PCSK9 Antibody in Subjects With LDL Receptor Abnormalities (TESLA)

Tracking Information
First Submitted Date ICMJE	February 27, 2012
First Posted Date ICMJE	May 1, 2012
Results First Submitted Date	August 28, 2015
Results First Posted Date	October 2, 2015
Last Update Posted Date	November 29, 2018
Actual Study Start Date ICMJE	April 5, 2012
Actual Primary Completion Date	January 31, 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: August 28, 2015)	Part A: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 [ Time Frame: Baseline and Week 12 ]LDL-C was quantified using the ultracentrifugation method.; Part B: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 [ Time Frame: Baseline and Week 12 ]LDL-C was quantified using the ultracentrifugation method.
Original Primary Outcome Measures ICMJE; (submitted: April 27, 2012)	Percent change from baseline in low density lipoprotein cholesterol (LDL-C) at week 12 for Part A and Part B. [ Time Frame: 12 weeks ]
Change History	Complete list of historical versions of study NCT01588496 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 19, 2015)	Part A: Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]LDL-C was quantified using the ultracentrifugation method.; Part A: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 [ Time Frame: Baseline and Week 12 ]; Part A: Percent Change From Baseline in Apolipoprotein B at Week 12 [ Time Frame: Baseline and Week 12 ]; Part A: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 [ Time Frame: Baseline and Week 12 ]; Part A: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 [ Time Frame: Baseline and Week 12 ]; Part A: Percentage of Participants With 15% or Greater Reduction in LDL-C From Baseline at Week 12 [ Time Frame: Baseline and Week 12 ]LDL-C was quantified using the ultracentrifugation method.; Part A: Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) at Week 12 [ Time Frame: Baseline and Week 12 ]; Part B: Percent Change From Baseline in LDL-C at the Mean of Weeks 6 and 12 [ Time Frame: Baseline and Weeks 6 and 12 ]LDL-C was quantified using the ultracentrifugation method.; Part B: Percent Change From Baseline in Apolipoprotein B at Week 12 [ Time Frame: Baseline and Week 12 ]; Part B: Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 6 and 12 [ Time Frame: Baseline and Weeks 6 and 12 ]; Part B: Percent Change From Baseline in Lipoprotein (a) at Week 12 [ Time Frame: Baseline and Week 12 ]; Part B: Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 6 and 12 [ Time Frame: Baseline and Weeks 6 and 12 ]
Original Secondary Outcome Measures ICMJE; (submitted: April 27, 2012)	Change from baseline in LDL-C at week 12 for Part A and Part B. [ Time Frame: 12 weeks ]; Percent change from baseline in non-high density lipoprotein cholesterol (non-HDL-C) at week 12 for Part A and Part B. [ Time Frame: 12 weeks ]; Percent change from baseline in apolipoprotein B (ApoB) at week 12 for Part A and Part B. [ Time Frame: 12 weeks ]; Percent change from baseline in the total cholesterol/HDL-C ratio at week 12 for Part A and Part B. [ Time Frame: 12 weeks ]; Percent change from baseline in ApoB/apolipoprotein A-1 (ApoA1) ratio at week 12 for Part A and Part B. [ Time Frame: 12 weeks ]; Response rate of subjects with 15% or greater reduction in LDL-C from baseline to Week 12 (Part A only). [ Time Frame: 12 weeks ]; Change from baseline in PCSK9 at week 12 for Part A and Part B. [ Time Frame: 12 weeks ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Trial Evaluating PCSK9 Antibody in Subjects With LDL Receptor Abnormalities
Official Title ICMJE	2-part, Phase 2/3 Study to Assess the Safety, Tolerability and Efficacy of AMG 145 in Subjects With Homozygous Familial Hypercholesterolemia. Part A - Open-label, Single-arm, Multicenter Pilot Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 in Subjects With Homozygous Familial Hypercholesterolemia. Part B - Double-blind, Randomized, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of AMG 145 in Subjects With Homozygous Familial Hypercholesterolemia
Brief Summary	A study to determine the safety, tolerability, and efficacy of evolocumab (AMG 145) in patients with homozygous familial hypercholesterolemia (HoFH).
Detailed Description	Study Masking: Part A: Open Label Part B: Double Blind
Study Type ICMJE	Interventional
Study Phase	Phase 2; Phase 3
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Homozygous Familial Hypercholesterolemia
Intervention ICMJE	Biological: Evolocumab Administered by subcutaneous injection Other Names: AMG 145 Repatha; Drug: Placebo Administered by subcutaneous injection
Study Arms	Experimental: Part A: Evolocumab Participants received open-label evolocumab 420 mg subcutaneously once a month for 12 weeks. Intervention: Biological: Evolocumab; Experimental: Part B: Evolocumab Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks. Intervention: Biological: Evolocumab; Placebo Comparator: Part B: Placebo Participants received double-blind placebo subcutaneously once a month for 12 weeks. Intervention: Drug: Placebo
Publications *	Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7. Review.; Raal FJ, Honarpour N, Blom DJ, Hovingh GK, Xu F, Scott R, Wasserman SM, Stein EA; TESLA Investigators. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial. Lancet. 2015 Jan 24;385(9965):341-50. doi: 10.1016/S0140-6736(14)61374-X. Epub 2014 Oct 1.; Stein EA, Honarpour N, Wasserman SM, Xu F, Scott R, Raal FJ. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation. 2013 Nov 5;128(19):2113-20. doi: 10.1161/CIRCULATIONAHA.113.004678. Epub 2013 Sep 6.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: November 14, 2013)	58
Original Estimated Enrollment ICMJE; (submitted: April 27, 2012)	66
Actual Study Completion Date	January 31, 2014
Actual Primary Completion Date	January 31, 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Males and females ≥ 12 to ≤ 80 years of age; Diagnosis of homozygous familial hypercholesterolemia; Stable lipid-lowering therapies for at least 4 weeks; LDL cholesterol ≥ 130 mg/dl (3.4 mmol/L); Triglyceride ≤ 400 mg/dL (4.5 mmol/L); Bodyweight of ≥ 40 kg at screening. Exclusion Criteria: LDL or plasma apheresis within 8 weeks prior to randomization; New York Heart Association (NYHA) class III or IV or last known left ventricular ejection fraction < 30%; Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months of randomization; Planned cardiac surgery or revascularization; Uncontrolled cardiac arrhythmia; Uncontrolled hypertension
Sex/Gender	Sexes Eligible for Study: All
Ages	12 Years to 80 Years (Child, Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Belgium, Canada, Czechia, France, Hong Kong, Italy, Lebanon, Netherlands, New Zealand, South Africa, Spain, United States
Removed Location Countries	Czech Republic
Administrative Information
NCT Number ICMJE	NCT01588496
Other Study ID Numbers ICMJE	20110233; 2011-005399-40 ( EudraCT Number )
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Amgen
Study Sponsor ICMJE	Amgen
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: MD Amgen
PRS Account	Amgen
Verification Date	November 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP