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

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ClinicalTrials.gov Identifier: NCT01588496

Recruitment Status : Completed

First Posted : May 1, 2012

Results First Posted : October 2, 2015

Last Update Posted : November 29, 2018

View this study on Beta.ClinicalTrials.gov

Sponsor:

Information provided by (Responsible Party):

Amgen

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
Enrollment	58

Participant Flow

Recruitment Details	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	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).


Arm/Group Title	Part A: Evolocumab	Part B: Placebo	Part B: Evolocumab
Arm/Group Description	Participants received open-label ev...	Participants received double-blind ...	Participants received double-blind ...
Arm/Group Description	Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Participants received double-blind placebo subcutaneously once a month for 12 weeks.	Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Period Title: Overall Study
Started	8	17	33
Received Treatment	8	16	33
Completed	8	16	33
Not Completed	0	1	0
Reason Not Completed
Withdrawal by Subject	0	1	0

Baseline Characteristics

Arm/Group Title		Part A: Evolocumab	Part B: Placebo	Part B: Evolocumab	Total
Arm/Group Description		Participants received open-label ev...	Participants received double-blind ...	Participants received double-blind ...	Total of all reporting groups
Arm/Group Description		Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.	Participants received double-blind placebo subcutaneously once a month for 12 weeks.	Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.	Total of all reporting groups
Overall Number of Baseline Participants		8	17	33	58
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	8 participants	17 participants	33 participants	58 participants
		34.3 (12.4)	32.8 (13.7)	30.3 (12.4)	31.6 (12.7)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	8 participants	17 participants	33 participants	58 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 Measure Type: Number Unit of measure: Participants	Number Analyzed	8 participants	17 participants	33 participants	58 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 Measure Type: Number Unit of measure: Participants	Number Analyzed	8 participants	17 participants	33 participants	58 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] Measure Type: Number Unit of measure: Participants	Number Analyzed	8 participants	17 participants	33 participants	58 participants
< 420 mg/dL		0	11	21	32
≥ 420 mg/dL		0	6	12	18
Missing		8	0	0	8
		[1] Measure Description: Participants in Part A were not stratified based on LDL-C level.
LDL-C Concentration ^[1] Mean (Standard Deviation) Unit of measure: mg/dL	Number Analyzed	8 participants	17 participants	33 participants	58 participants
Part A		441.7 (113.3)	NA ^[2] (NA)	NA ^[2] (NA)	441.7 (113.3)
Part B		NA ^[3] (NA)	335.8 (146.0)	356.0 (134.5)	349.4 (137.2)
		[1] Measure Description: 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] Mean (Standard Deviation) Unit of measure: mg/dL	Number Analyzed	8 participants	17 participants	33 participants	58 participants
Part A		470.6 (117.8)	NA ^[2] (NA)	NA ^[2] (NA)	470.6 (117.8)
Part B		NA ^[3] (NA)	358.9 (149.1)	374.9 (136.9)	369.7 (139.6)
		[1] Measure Description: 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] Mean (Standard Deviation) Unit of measure: mg/dL	Number Analyzed	8 participants	17 participants	33 participants	58 participants
Part A		269.1 (53.0)	NA ^[2] (NA)	NA ^[2] (NA)	269.1 (53.0)
Part B		NA ^[3] (NA)	208.6 (79.5)	208.3 (68.4)	208.4 (71.4)
		[1] Measure Description: 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] Mean (Standard Deviation) Unit of measure: Ratio	Number Analyzed	8 participants	17 participants	33 participants	58 participants
Part A		15.988 (5.107)	NA ^[2] (NA)	NA ^[2] (NA)	15.988 (5.107)
Part B		NA ^[3] (NA)	12.101 (6.619)	11.972 (6.387)	12.014 (6.395)
		[1] Measure Description: 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] Mean (Standard Deviation) Unit of measure: Ratio	Number Analyzed	8 participants	17 participants	33 participants	58 participants
Part A		2.800 (0.729)	NA ^[2] (NA)	NA ^[2] (NA)	2.800 (0.729)
Part B		NA ^[3] (NA)	2.053 (0.967)	2.098 (1.046)	2.084 (1.011)
		[1] Measure Description: 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 Median (Inter-Quartile Range) Unit of measure: nmol/L	Number Analyzed	8 participants	17 participants	33 participants	58 participants
Part A		246.5 (61.5 to 276)	NA ^[1] (NA to NA)	NA ^[1] (NA to NA)	246.5 (61.5 to 276)
Part B		NA ^[2] (NA to NA)	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] Mean (Standard Deviation) Unit of measure: ng/mL	Number Analyzed	8 participants	17 participants	33 participants	58 participants
Part A		598.6 (121.1)	NA ^[2] (NA)	NA ^[2] (NA)	598.6 (121.1)
Part B		NA ^[3] (NA)	674.2 (180.0)	640.3 (207.5)	651.4 (197.7)
		[1] Measure Description: Data are provided for the full analysis set [2] Not applicable for Part B participants [3] Not applicable for Part A participants

Outcome Measures

1.Primary Outcome


Title	Part A: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
Description	LDL-C was quantified using the ultracentrifugation method.
Description	LDL-C was quantified using the ultracentrifugation method.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Part A full analysis set (all enrolled participants who received at least 1 dose of evolocumab)


Arm/Group Title	Part A: Evolocumab
Arm/Group Description:	Participants received open-label ev...
Arm/Group Description:	Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.
Overall Number of Participants Analyzed	8
Mean (Standard Error) Unit of Measure: percent change
	-16.5 (6.7)

2.Primary Outcome


Title	Part B: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
Description	LDL-C was quantified using the ultracentrifugation method.
Description	LDL-C was quantified using the ultracentrifugation method.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Part B full analysis set (all enrolled participants who received at least 1 dose of investigational product)


Arm/Group Title	Part B: Placebo	Part B: Evolocumab
Arm/Group Description:	Participants received double-blind ...	Participants received double-blind ...
Arm/Group Description:	Participants received double-blind placebo subcutaneously once a month for 12 weeks.	Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Overall Number of Participants Analyzed	16	33
Least Squares Mean (Standard Error) Unit of Measure: percent change
	7.88 (5.26)	-23.05 (3.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part B: Placebo, Part B: Evolocumab
	Comments	LDL-C lowering was analyzed by comparing evolocumab and placebo. Statistical analysis was 2-sided with a significance level of 0.05.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, baseline LDL-C level (< 420 vs ≥ 420 mg/dL), scheduled visit and the interaction of treatment with scheduled visit.

Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-30.93
	Confidence Interval	(2-Sided) 95% -43.86 to -18.00
	Parameter Dispersion	Type: Standard Error of the Mean Value: 6.42
	Estimation Comments	Placebo is the reference

3.Secondary Outcome


Title	Part A: Change From Baseline in LDL-C at Week 12
Description	LDL-C was quantified using the ultracentrifugation method.
Description	LDL-C was quantified using the ultracentrifugation method.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Part A full analysis set


Arm/Group Title	Part A: Evolocumab
Arm/Group Description:	Participants received open-label ev...
Arm/Group Description:	Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.
Overall Number of Participants Analyzed	8
Mean (Standard Error) Unit of Measure: mg/dL
	-70.6 (32.3)

4.Secondary Outcome


Title	Part A: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Part A full analysis set


Arm/Group Title	Part A: Evolocumab
Arm/Group Description:	Participants received open-label ev...
Arm/Group Description:	Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.
Overall Number of Participants Analyzed	8
Mean (Standard Error) Unit of Measure: percent change
	-16.6 (6.5)

5.Secondary Outcome


Title	Part A: Percent Change From Baseline in Apolipoprotein B at Week 12
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Part A full analysis set


Arm/Group Title	Part A: Evolocumab
Arm/Group Description:	Participants received open-label ev...
Arm/Group Description:	Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.
Overall Number of Participants Analyzed	8
Mean (Standard Error) Unit of Measure: percent change
	-14.9 (5.0)

6.Secondary Outcome


Title	Part A: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Part A full analysis set


Arm/Group Title	Part A: Evolocumab
Arm/Group Description:	Participants received open-label ev...
Arm/Group Description:	Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.
Overall Number of Participants Analyzed	8
Mean (Standard Error) Unit of Measure: percent change
	-18.319 (6.058)

7.Secondary Outcome


Title	Part A: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Part A full analysis set


Arm/Group Title	Part A: Evolocumab
Arm/Group Description:	Participants received open-label ev...
Arm/Group Description:	Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.
Overall Number of Participants Analyzed	8
Mean (Standard Error) Unit of Measure: percent change
	-15.65 (4.690)

8.Secondary Outcome


Title	Part A: Percentage of Participants With 15% or Greater Reduction in LDL-C From Baseline at Week 12
Description	LDL-C was quantified using the ultracentrifugation method.
Description	LDL-C was quantified using the ultracentrifugation method.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Part A full analysis set


Arm/Group Title	Part A: Evolocumab
Arm/Group Description:	Participants received open-label ev...
Arm/Group Description:	Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.
Overall Number of Participants Analyzed	8
Measure Type: Number Unit of Measure: percentage of participants
	50.0

9.Secondary Outcome


Title	Part A: Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) at Week 12
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Part A full analysis set


Arm/Group Title	Part A: Evolocumab
Arm/Group Description:	Participants received open-label ev...
Arm/Group Description:	Participants received open-label evolocumab 420 mg subcutaneously (SC) once a month (QM) for 12 weeks.
Overall Number of Participants Analyzed	8
Mean (Standard Error) Unit of Measure: ng/mL
	-151.3 (81.7)

10.Secondary Outcome


Title	Part B: Percent Change From Baseline in LDL-C at the Mean of Weeks 6 and 12
Description	LDL-C was quantified using the ultracentrifugation method.
Description	LDL-C was quantified using the ultracentrifugation method.
Time Frame	Baseline and Weeks 6 and 12

Outcome Measure Data

Analysis Population Description

Part B full analysis set


Arm/Group Title	Part B: Placebo	Part B: Evolocumab
Arm/Group Description:	Participants received double-blind ...	Participants received double-blind ...
Arm/Group Description:	Participants received double-blind placebo subcutaneously once a month for 12 weeks.	Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Overall Number of Participants Analyzed	16	33
Least Squares Mean (Standard Error) Unit of Measure: percent change
	4.22 (4.56)	-25.56 (3.28)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part B: Placebo, Part B: Evolocumab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, baseline LDL-C level (< 420 vs ≥ 420 mg/dL), scheduled visit and the interaction of treatment with scheduled visit.

Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-29.78
	Confidence Interval	(2-Sided) 95% -40.94 to -18.62
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.54
	Estimation Comments	Placebo is the reference

11.Secondary Outcome


Title	Part B: Percent Change From Baseline in Apolipoprotein B at Week 12
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Part B full analysis set


Arm/Group Title	Part B: Placebo	Part B: Evolocumab
Arm/Group Description:	Participants received double-blind ...	Participants received double-blind ...
Arm/Group Description:	Participants received double-blind placebo subcutaneously once a month for 12 weeks.	Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Overall Number of Participants Analyzed	16	33
Least Squares Mean (Standard Error) Unit of Measure: percent change
	3.97 (4.74)	-19.17 (3.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part B: Placebo, Part B: Evolocumab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, baseline LDL-C level (< 420 vs ≥ 420 mg/dL), scheduled visit and the interaction of treatment with scheduled visit.

Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-23.14
	Confidence Interval	(2-Sided) 95% -34.83 to -11.45
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.81
	Estimation Comments	Placebo is the reference

12.Secondary Outcome


Title	Part B: Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 6 and 12
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline and Weeks 6 and 12

Outcome Measure Data

Analysis Population Description

Part B full analysis set


Arm/Group Title	Part B: Placebo	Part B: Evolocumab
Arm/Group Description:	Participants received double-blind ...	Participants received double-blind ...
Arm/Group Description:	Participants received double-blind placebo subcutaneously once a month for 12 weeks.	Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Overall Number of Participants Analyzed	16	33
Least Squares Mean (Standard Error) Unit of Measure: percent change
	2.65 (4.42)	-20.24 (3.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part B: Placebo, Part B: Evolocumab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, baseline LDL-C level (< 420 vs ≥ 420 mg/dL), scheduled visit and the interaction of treatment with scheduled visit.

Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-22.89
	Confidence Interval	(2-Sided) 95% -33.72 to -12.05
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.38
	Estimation Comments	Placebo is the reference

13.Secondary Outcome


Title	Part B: Percent Change From Baseline in Lipoprotein (a) at Week 12
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Part B full anlaysis set


Arm/Group Title	Part B: Placebo	Part B: Evolocumab
Arm/Group Description:	Participants received double-blind ...	Participants received double-blind ...
Arm/Group Description:	Participants received double-blind placebo subcutaneously once a month for 12 weeks.	Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Overall Number of Participants Analyzed	16	33
Least Squares Mean (Standard Error) Unit of Measure: percent change
	2.43 (5.49)	-9.40 (4.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part B: Placebo, Part B: Evolocumab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.088
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
	Method	Repeated measures linear effects model
	Comments	Model includes treatment group, baseline LDL-C level (< 420 vs ≥ 420 mg/dL), scheduled visit and the interaction of treatment with scheduled visit.

Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-11.83
	Confidence Interval	(2-Sided) 95% -25.48 to 1.82
	Parameter Dispersion	Type: Standard Error of the Mean Value: 6.77
	Estimation Comments	Placebo is the reference

14.Secondary Outcome


Title	Part B: Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 6 and 12
Description	[Not Specified]
Description	[Not Specified]
Time Frame	Baseline and Weeks 6 and 12

Outcome Measure Data

Analysis Population Description

Part B full analysis set


Arm/Group Title	Part B: Placebo	Part B: Evolocumab
Arm/Group Description:	Participants received double-blind ...	Participants received double-blind ...
Arm/Group Description:	Participants received double-blind placebo subcutaneously once a month for 12 weeks.	Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
Overall Number of Participants Analyzed	16	33
Least Squares Mean (Standard Error) Unit of Measure: percent change
	-1.43 (4.78)	-12.71 (3.53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part B: Placebo, Part B: Evolocumab
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.088
	Comments	Multiplicity adjusted p-value is significant if less than the familywise error rate of 0.05.
	Method	Repeated measures linear effects
	Comments	Model includes treatment group, baseline LDL-C level (< 420 vs ≥ 420 mg/dL), scheduled visit and the interaction of treatment with scheduled visit.

Method of Estimation	Estimation Parameter	LS Mean Treatment Difference
	Estimated Value	-11.27
	Confidence Interval	(2-Sided) 95% -23.11 to 0.56
	Parameter Dispersion	Type: Standard Error of the Mean Value: 5.86
	Estimation Comments	Placebo is the reference

Adverse Events

Time Frame	12 weeks
Adverse Event Reporting Description	Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold. MedDRA 16.0 was used to code adverse events in Part A; MedDRA 16.1 was used to code adverse events in Part B.

Arm/Group Title	Part A: OL Evolocumab	Part B: DB Placebo	Part B: DB Evolocumab
Arm/Group Description	Participants received open-label (O...	Participants received double-blind ...	Participants received double-blind ...
Arm/Group Description	Participants received open-label (OL) evolocumab 420 mg subcutaneously once a month for 12 weeks.	Participants received double-blind (DB) placebo subcutaneously once a month for 12 weeks.	Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks.
All-Cause Mortality
	Part A: OL Evolocumab	Part B: DB Placebo	Part B: DB Evolocumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--
Serious Adverse Events Serious Adverse Events
	Part A: OL Evolocumab	Part B: DB Placebo	Part B: DB Evolocumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/8 (0.00%)	0/16 (0.00%)	0/33 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Part A: OL Evolocumab	Part B: DB Placebo	Part B: DB Evolocumab
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	4/8 (50.00%)	10/16 (62.50%)	11/33 (33.33%)
Cardiac disorders
Palpitations ^† 1	0/8 (0.00%)	1/16 (6.25%)	0/33 (0.00%)
Gastrointestinal disorders
Abdominal pain ^† 1	0/8 (0.00%)	1/16 (6.25%)	1/33 (3.03%)
Abdominal pain upper ^† 1	0/8 (0.00%)	1/16 (6.25%)	0/33 (0.00%)
Dyspepsia ^† 1	1/8 (12.50%)	0/16 (0.00%)	0/33 (0.00%)
Nausea ^† 1	0/8 (0.00%)	2/16 (12.50%)	0/33 (0.00%)
General disorders
Chest pain ^† 1	0/8 (0.00%)	1/16 (6.25%)	1/33 (3.03%)
Fatigue ^† 1	0/8 (0.00%)	1/16 (6.25%)	0/33 (0.00%)
Injection site pain ^† 1	0/8 (0.00%)	1/16 (6.25%)	0/33 (0.00%)
Medical device site reaction ^† 1	0/8 (0.00%)	1/16 (6.25%)	0/33 (0.00%)
Pain ^† 1	1/8 (12.50%)	0/16 (0.00%)	0/33 (0.00%)
Infections and infestations
Bronchitis ^† 1	1/8 (12.50%)	0/16 (0.00%)	0/33 (0.00%)
Gastroenteritis ^† 1	0/8 (0.00%)	0/16 (0.00%)	2/33 (6.06%)
Influenza ^† 1	0/8 (0.00%)	0/16 (0.00%)	3/33 (9.09%)
Nasopharyngitis ^† 1	0/8 (0.00%)	0/16 (0.00%)	2/33 (6.06%)
Upper respiratory tract infection ^† 1	0/8 (0.00%)	1/16 (6.25%)	3/33 (9.09%)
Investigations
Blood creatine phosphokinase increased ^† 1	0/8 (0.00%)	1/16 (6.25%)	0/33 (0.00%)
Weight decreased ^† 1	0/8 (0.00%)	1/16 (6.25%)	0/33 (0.00%)
Musculoskeletal and connective tissue disorders
Back pain ^† 1	0/8 (0.00%)	1/16 (6.25%)	0/33 (0.00%)
Nervous system disorders
Dizziness ^† 1	0/8 (0.00%)	1/16 (6.25%)	0/33 (0.00%)
Headache ^† 1	0/8 (0.00%)	1/16 (6.25%)	0/33 (0.00%)
Presyncope ^† 1	0/8 (0.00%)	1/16 (6.25%)	0/33 (0.00%)
Reproductive system and breast disorders
Dysmenorrhoea ^† 1	0/8 (0.00%)	1/16 (6.25%)	1/33 (3.03%)
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic ^† 1	1/8 (12.50%)	0/16 (0.00%)	0/33 (0.00%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA 16.0/16.1

Limitations and Caveats

[Not Specified]

More Information

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 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

Layout table for Results Point of Contact information

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

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

Layout table for additonal information

Responsible Party:	Amgen
ClinicalTrials.gov Identifier:	NCT01588496
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:	November 29, 2018

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