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

• ClinicalTrials.gov Identifier: NCT01588496
• Recruitment Status: Completed
• First Posted: May 1, 2012
• Results First Posted: October 2, 2015
• Last Update Posted: November 29, 2018
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: February 27, 2012
• First Posted Date: 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: April 5, 2012
• Actual Primary Completion Date: January 31, 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 ]

Current Secondary Outcome Measures (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 (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 Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial Evaluating PCSK9 Antibody in Subjects With LDL Receptor Abnormalities
• Official Title: 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: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Homozygous Familial Hypercholesterolemia

Intervention

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 14, 2013): 58
• Original Estimated Enrollment (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

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: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: 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: NCT01588496
• Other Study ID Numbers: 20110233; 2011-005399-40 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Amgen
• Original Responsible Party: Global Development Leader, Amgen Inc.
• Current Study Sponsor: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: November 2018