Homozygous Familial HypercholesterolemiaPhase 2/3TESLANCT01588496
Trial Evaluating PCSK9 Antibody in Subjects With LDL Receptor Abnormalities
A Phase 2/3 study testing Evolocumab in people with Homozygous Familial Hypercholesterolemia, run by Amgen at 21 sites in 12 countries.
Trial summary
A study to determine the safety, tolerability, and efficacy of evolocumab (AMG 145) in patients with homozygous familial hypercholesterolemia (HoFH). Read more about this study
- Who is it for?
- Ages 12 to 80 years
- Conditions the study is for
- Homozygous Familial Hypercholesterolemia
- What is being tested?
- Evolocumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 58 participants
- Where
- 21 sitesin 12 countries
- Study dates
- 5 Apr 2012to 31 Jan 2014
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
21 sites in 12 countries.
21 sites in 12 countries
Czechia3 sites
Research Site
Brno, 656 91
Research Site
Hradec Králové, 500 05
Research Site
Uherské Hradiště, 686 01
Spain3 sites
Research Site
Córdoba, Andalusia, 14004
Research Site
Lugo, Galicia, 27003
Research Site
Madrid, 28040
United States2 sites
Research Site
Cincinnati, Ohio, 45227
Research Site
New York, New York, 10032
Canada2 sites
Research Site
Chicoutimi, Quebec, G7H 7K9
Research Site
London, Ontario, N6A 5K8
South Africa2 sites
Research Site
Johannesburg, Gauteng, 2193
Research Site
Observatory, Western Cape, 7925
About this study
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
A study to determine the safety, tolerability, and efficacy of evolocumab (AMG 145) in patients with homozygous familial hypercholesterolemia (HoFH).
Read the detailed description
Study Masking:
Part A: Open Label Part B: Double Blind
- Conditions
- Homozygous Familial Hypercholesterolemia
- Being tested
- Evolocumab, Placebo
- Keywords
- hypercholesterolemia, familial hypercholesterolemia, homozygous familial hypercholesterolemia
- Medical subject headings
- Homozygous Familial Hypercholesterolemia, Hypercholesterolemia, Hyperlipoproteinemia Type II
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EvolocumabBiological
Also called AMG 145, Repatha
Administered by subcutaneous injection
PlaceboDrug
Administered by subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Part A: Evolocumab | Experimental | Participants received open-label evolocumab 420 mg subcutaneously once a month for 12 weeks. Receives: Biological: Evolocumab |
| Part B: Evolocumab | Experimental | Participants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks. Receives: Biological: Evolocumab |
| Part B: Placebo | Placebo comparator | Participants received double-blind placebo subcutaneously once a month for 12 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
LDL-C was quantified using the ultracentrifugation method.
Measured: Baseline and Week 12
Part B: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12
LDL-C was quantified using the ultracentrifugation method.
Measured: Baseline and Week 12
Secondary outcomes (12)
Part A: Change From Baseline in LDL-C at Week 12
LDL-C was quantified using the ultracentrifugation method.
Measured: Baseline and Week 12
Part A: Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 12
Measured: Baseline and Week 12
Part A: Percent Change From Baseline in Apolipoprotein B at Week 12
Measured: Baseline and Week 12
Part A: Percent Change From Baseline in the Total Cholesterol/HDL-C Ratio at Week 12
Measured: Baseline and Week 12
Part A: Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
Measured: Baseline and Week 12
Part A: Percentage of Participants With 15% or Greater Reduction in LDL-C From Baseline at Week 12
LDL-C was quantified using the ultracentrifugation method.
Measured: Baseline and Week 12
Part A: Change From Baseline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) at Week 12
Measured: Baseline and Week 12
Part B: Percent Change From Baseline in LDL-C at the Mean of Weeks 6 and 12
LDL-C was quantified using the ultracentrifugation method.
Measured: Baseline and Weeks 6 and 12
Part B: Percent Change From Baseline in Apolipoprotein B at Week 12
Measured: Baseline and Week 12
Part B: Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 6 and 12
Measured: Baseline and Weeks 6 and 12
Part B: Percent Change From Baseline in Lipoprotein (a) at Week 12
Measured: Baseline and Week 12
Part B: Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 6 and 12
Measured: Baseline and Weeks 6 and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2012 (estimated)
- Study start5 Apr 2012
- Primary completion31 Jan 2014
- Study completion31 Jan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Homozygous Familial HypercholesterolemiaStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01588496
- Sponsor's protocol ID
- 20110233
- Other IDs
- 2011-005399-40
- Acronym
- TESLA
- Status last verified
- Nov 2018
- First submitted
- 27 Feb 2012
- Last updated
- 29 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
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.
PubMed 29353350Raal 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.
PubMed 25282520Stein 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.
PubMed 24014831
Study at a glance
From the registry record, last updated by the sponsor on 29 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01588496
- Acronym / sponsor ID
- TESLA / 20110233
- Conditions
- Homozygous Familial Hypercholesterolemia
- Keywords
- hypercholesterolemia, familial hypercholesterolemia, homozygous familial hypercholesterolemia
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 5 Apr 2012 (actual)
- Primary completion
- 31 Jan 2014 (actual)
- Study completion
- 31 Jan 2014 (actual)
- First posted
- 1 May 2012 (estimated)
- Results
- Posted 2 Oct 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part A: Evolocumab | Experimental | Biological: EvolocumabParticipants received open-label evolocumab 420 mg subcutaneously once a month for 12 weeks. |
| Part B: Evolocumab | Experimental | Biological: EvolocumabParticipants received double-blind evolocumab 420 mg subcutaneously once a month for 12 weeks. |
| Part B: Placebo | Placebo comparator | Drug: PlaceboParticipants received double-blind placebo subcutaneously once a month for 12 weeks. |
Who may qualify
- Ages
- 12 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EvolocumabAlso: AMG 145, RepathaAdministered by subcutaneous injection | Biological | Part A: Evolocumab, Part B: Evolocumab |
| PlaceboAdministered by subcutaneous injection | Drug | Part B: Placebo |
Primary outcome
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.
12 secondary outcomes
Part A: Change From Baseline in LDL-C at Week 12
Time frame: Baseline and Week 12
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 29353350Kasichayanula 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.
- Derived from this study: PubMed 25282520Raal 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.
- Derived from this study: PubMed 24014831Stein 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.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
21 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Evolocumab in people with Homozygous Familial Hypercholesterolemia, run by Amgen at 21 sites in 12 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Czechia, Spain, United States, Belgium, Canada and 7 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 12 (time frame: Baseline and Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01588496, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Nov 2018.