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

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	Homozygous Familial Hypercholesterolemia
Interventions:	Biological: Evolocumab; Drug: Placebo

  Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Male and female adults and adolescents ages ≥ 12 to ≤ 65 years (≥ 12 to ≤ 80 years in Part B) with a diagnosis of homozygous familial hypercholesterolemia (HoFH) were eligible for this study. The first participant enrolled on 05 April 2012 and the last participant enrolled on 08 November 2013.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Part A was an open-label, single-arm, multicenter pilot study. Part B was a double-blind, randomized, placebo-controlled, multicenter study with expanded enrollment. In Part B participants were randomized in a 1:2 allocation stratified on the basis of screening low-density lipoprotein cholesterol (LDL-C) (< 420 mg/dL vs ≥ 420 mg/dL).

Reporting Groups

	Description
Part A: Evolocumab	Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.
Part B: Placebo	Participants received double-blind placebo subcutaneously once a month for 12 weeks.
Part B: Evolocumab	Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.

Participant Flow:   Overall Study

	Part A: Evolocumab	Part B: Placebo	Part B: Evolocumab
STARTED	8	17	33
Received Treatment	8	16	33
COMPLETED	8	16	33
NOT COMPLETED	0	1	0
Withdrawal by Subject	0	1	0

  Baseline Characteristics

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Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups

	Description
Part A: Evolocumab	Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.
Part B: Placebo	Participants received double-blind placebo subcutaneously once a month for 12 weeks.
Part B: Evolocumab	Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Total	Total of all reporting groups

Baseline Measures

	Part A: Evolocumab	Part B: Placebo	Part B: Evolocumab	Total
Overall Participants Analyzed; [Units: Participants]	8	17	33	58
Age; [Units: Years]; Mean (Standard Deviation)	34.3 (12.4)	32.8 (13.7)	30.3 (12.4)	31.6 (12.7)
Sex: Female, Male; [Units: Participants]; Count of Participants
Female	2 25.0%	8 47.1%	16 48.5%	26 44.8%
Male	6 75.0%	9 52.9%	17 51.5%	32 55.2%
Race/Ethnicity, Customized; [Units: Participants]
American Indian or Alaska Native	0	0	0	0
Asian	0	1	1	2
Black or African American	0	0	0	0
Native Hawaiian or Other Pacific Islander	0	0	0	0
White	8	16	29	53
Other	0	0	3	3
Race/Ethnicity, Customized; [Units: Participants]
Hispanic or Latino	0	0	1	1
Not Hispanic or Latino	8	17	32	57
Stratification Factor: Low-Density Lipoprotein Cholesterol (LDL-C) Level [1]; [Units: Participants]
< 420 mg/dL	0	11	21	32
≥ 420 mg/dL	0	6	12	18
Missing	8	0	0	8
[1] Participants in Part A were not stratified based on LDL-C level.
LDL-C Concentration [1] [2] [3]; [Units: mg/dL]; Mean (Standard Deviation)
Part A	441.7 (113.3)	NA [2]	NA [2]	441.7 (113.3)
Part B	NA [3]	335.8 (146.0)	356.0 (134.5)	349.4 (137.2)
[1] LDL-C was quantified using the ultracentrifugation method. Data are provided for the full analysis set (all enrolled participants who received at least 1 dose of evolocumab (Part A) or all randomized participants who received at least 1 dose of investigational product (Part B). [2] Not applicable for Part B participants [3] Not applicable for Part A participants
Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration [1] [2] [3]; [Units: mg/dL]; Mean (Standard Deviation)
Part A	470.6 (117.8)	NA [2]	NA [2]	470.6 (117.8)
Part B	NA [3]	358.9 (149.1)	374.9 (136.9)	369.7 (139.6)
[1] Data are provided for the full analysis set [2] Not applicable for Part B participants [3] Not applicable for Part A participants
Apolipoprotein B Concentration [1] [2] [3]; [Units: mg/dL]; Mean (Standard Deviation)
Part A	269.1 (53.0)	NA [2]	NA [2]	269.1 (53.0)
Part B	NA [3]	208.6 (79.5)	208.3 (68.4)	208.4 (71.4)
[1] Data are provided for the full analysis set [2] Not applicable for Part B participants [3] Not applicable for Part A participants
Total Cholesterol/HDL-C Ratio [1] [2] [3]; [Units: Ratio]; Mean (Standard Deviation)
Part A	15.988 (5.107)	NA [2]	NA [2]	15.988 (5.107)
Part B	NA [3]	12.101 (6.619)	11.972 (6.387)	12.014 (6.395)
[1] Data are provided for the full analysis set [2] Not applicable for Part B participants [3] Not applicable for Part A participants
Apolipoprotein B/Apolipoprotein A1 Ratio [1] [2] [3]; [Units: Ratio]; Mean (Standard Deviation)
Part A	2.800 (0.729)	NA [2]	NA [2]	2.800 (0.729)
Part B	NA [3]	2.053 (0.967)	2.098 (1.046)	2.084 (1.011)
[1] Data are provided for the full analysis set [2] Not applicable for Part B participants [3] Not applicable for Part A participants
Lipoprotein(a) Concentration [1] [2]; [Units: nmol/L]; Median (Inter-Quartile Range)
Part A	246.5; (61.5 to 276)	NA [1]	NA [1]	246.5; (61.5 to 276)
Part B	NA [2]	127.5; (79.5 to 200.5)	76.0; (25.5 to 145.0)	100.5; (31.0 to 146.0)
[1] Not applicable for Part B participants [2] Not applicable for Part A participants
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Concentration [1] [2] [3]; [Units: ng/mL]; Mean (Standard Deviation)
Part A	598.6 (121.1)	NA [2]	NA [2]	598.6 (121.1)
Part B	NA [3]	674.2 (180.0)	640.3 (207.5)	651.4 (197.7)
[1] Data are provided for the full analysis set [2] Not applicable for Part B participants [3] Not applicable for Part A participants

  Outcome Measures

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1. Primary:

Part A: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 [ Time Frame: Baseline and Week 12 ]

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2. Primary:

Part B: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 [ Time Frame: Baseline and Week 12 ]

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3. Secondary:

Part A: Change From Baseline in LDL-C at Week 12 [ Time Frame: Baseline and Week 12 ]

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4. Secondary:

Part A: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12 [ Time Frame: Baseline and Week 12 ]

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5. Secondary:

Part A: Percent Change From Baseline in Apolipoprotein B at Week 12 [ Time Frame: Baseline and Week 12 ]

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6. Secondary:

Part A: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12 [ Time Frame: Baseline and Week 12 ]

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7. Secondary:

Part A: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12 [ Time Frame: Baseline and Week 12 ]

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8. Secondary:

Part A: Percentage of Participants With 15% or Greater Reduction in LDL-C From Baseline at Week 12 [ Time Frame: Baseline and Week 12 ]

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9. Secondary:

Part A: Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) at Week 12 [ Time Frame: Baseline and Week 12 ]

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10. Secondary:

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 ]

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11. Secondary:

Part B: Percent Change From Baseline in Apolipoprotein B at Week 12 [ Time Frame: Baseline and Week 12 ]

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12. Secondary:

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 ]

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13. Secondary:

Part B: Percent Change From Baseline in Lipoprotein (a) at Week 12 [ Time Frame: Baseline and Week 12 ]

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14. Secondary:

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 ]

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  Serious Adverse Events

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  Other Adverse Events

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  Limitations and Caveats

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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information

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Certain Agreements:  

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is: The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo. The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo. Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.; Restriction Description: The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.

Results Point of Contact:  

Name/Title: Study Director
Organization: Amgen Inc.
phone: 866-572-6436

Publications:

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.

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.

Responsible Party:	Amgen
ClinicalTrials.gov Identifier:	NCT01588496 History of Changes
Other Study ID Numbers:	20110233; 2011-005399-40 ( EudraCT Number )
First Submitted:	February 27, 2012
First Posted:	May 1, 2012
Results First Submitted:	August 28, 2015
Results First Posted:	October 2, 2015
Last Update Posted:	March 15, 2017