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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT01588496
First received: February 27, 2012
Last updated: November 19, 2015
Last verified: November 2015
Results First Received: August 28, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, 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.
No text entered.

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  
Number of Participants  
[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)  
Gender  
[units: participants]
       
Female     2     8     16     26  
Male     6     9     17     32  
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  
LDL-C Concentration [2]
[units: mg/dL]
Mean (Standard Deviation)
       
Part A     441.7  (113.3)     NA [3]   NA [3]   441.7  (113.3)  
Part B     NA [4]   335.8  (146.0)     356.0  (134.5)     349.4  (137.2)  
Non-High-Density Lipoprotein Cholesterol (non-HDL-C) Concentration [5]
[units: mg/dL]
Mean (Standard Deviation)
       
Part A     470.6  (117.8)     NA [3]   NA [3]   470.6  (117.8)  
Part B     NA [4]   358.9  (149.1)     374.9  (136.9)     369.7  (139.6)  
Apolipoprotein B Concentration [5]
[units: mg/dL]
Mean (Standard Deviation)
       
Part A     269.1  (53.0)     NA [3]   NA [3]   269.1  (53.0)  
Part B     NA [4]   208.6  (79.5)     208.3  (68.4)     208.4  (71.4)  
Total Cholesterol/HDL-C Ratio [5]
[units: ratio]
Mean (Standard Deviation)
       
Part A     15.988  (5.107)     NA [3]   NA [3]   15.988  (5.107)  
Part B     NA [4]   12.101  (6.619)     11.972  (6.387)     12.014  (6.395)  
Apolipoprotein B/Apolipoprotein A1 Ratio [5]
[units: ratio]
Mean (Standard Deviation)
       
Part A     2.800  (0.729)     NA [3]   NA [3]   2.800  (0.729)  
Part B     NA [4]   2.053  (0.967)     2.098  (1.046)     2.084  (1.011)  
Lipoprotein(a) Concentration  
[units: nmol/L]
Median (Inter-Quartile Range)
       
Part A     246.5  
  (61.5 to 276)  
  NA  
  [3]
  NA  
  [3]
  246.5  
  (61.5 to 276)  
Part B     NA  
  [4]
  127.5  
  (79.5 to 200.5)  
  76.0  
  (25.5 to 145.0)  
  100.5  
  (31.0 to 146.0)  
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Concentration [5]
[units: ng/mL]
Mean (Standard Deviation)
       
Part A     598.6  (121.1)     NA [3]   NA [3]   598.6  (121.1)  
Part B     NA [4]   674.2  (180.0)     640.3  (207.5)     651.4  (197.7)  
[1] Participants in Part A were not stratified based on LDL-C level.
[2] 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).
[3] Not applicable for Part B participants
[4] Not applicable for Part A participants
[5] Data are provided for the full analysis set



  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 ]

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

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

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 ]

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

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

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

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 ]

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

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 ]

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

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 ]

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

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 ]


  Serious Adverse Events


  Other Adverse Events


  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:
unchecked 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.
unchecked 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.


Results Point of Contact:  
Name/Title: Study Director
Organization: Amgen Inc.
phone: 866-572-6436


Publications:

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01588496     History of Changes
Other Study ID Numbers: 20110233
2011-005399-40 ( EudraCT Number )
Study First Received: February 27, 2012
Results First Received: August 28, 2015
Last Updated: November 19, 2015
Health Authority: Czech Republic: State Institute for Drug Control (SUKL)
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Italy: Ministry of Health
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Netherlands: Centrale Commissie Mensgebonden Onderzoek (CCMO
Turkey: Ministry of Health, the Republic of Turkey
South Africa: MCC
Brazil: ANVISA (Agencia Nacional de Vigilancia Sanitária)
Hong Kong: Department of Health
New Zealand: MEDSAFE (New Zealand Medicines and Medical Devices Safety Authority)
Canada: Canadian Agency is Health Canada _ Biologics and Genetic Therapies Directorate.
United States: Food and Drug Administration
Lebanon: Institutional Review Board