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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01624142




Registration number
NCT01624142
Ethics application status
Date submitted
5/06/2012
Date registered
20/06/2012
Date last updated
28/05/2024

Titles & IDs
Public title
Trial Assessing Long Term USe of PCSK9 Inhibition in Subjects With Genetic LDL Disorders
Scientific title
A Multicenter, Open-label Study to Assess the Long-term Safety, Tolerability, and Efficacy of Evolocumab (AMG145) on LDL-C in Subjects With Severe Familial Hypercholesterolemia
Secondary ID [1] 0 0
2011-005400-15
Secondary ID [2] 0 0
20110271
Universal Trial Number (UTN)
Trial acronym
TAUSSIG
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Severe Familial Hypercholesterolemia 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Evolocumab

Experimental: Evolocumab - Participants received 420 mg evolocumab every month (participants not on lipid apheresis) or every 2 weeks (participants on lipid apheresis) for up to 5 years. Participants could switch dosing regimens at week 12 or 24 based on LDL-C and serum unbound proprotein convertase subtilisin/kexin type 9 (PCSK9) levels.


Treatment: Other: Evolocumab
Evolocumab was administered by subcutaneous injection either once a month (QM) or once every two weeks (Q2W).
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Adverse Events
Timepoint [1] 0 0
From first dose of study drug in Study 20110271 up to 30 days after the last dose or until the end of study date, whichever was earlier; median duration of treatment was 48.7 months.
Secondary outcome [1] 0 0
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C)
Timepoint [1] 0 0
Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216
Secondary outcome [2] 0 0
Percent Change From Baseline in Non-high-density Lipoprotein Cholesterol (Non-HDL-C)
Timepoint [2] 0 0
Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216
Secondary outcome [3] 0 0
Percent Change From Baseline in Lipoprotein (a)
Timepoint [3] 0 0
Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216
Secondary outcome [4] 0 0
Percent Change From Baseline in Apolipoprotein B
Timepoint [4] 0 0
Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216
Secondary outcome [5] 0 0
Percent Change From Baseline in Total Cholesterol/HDL-C Ratio
Timepoint [5] 0 0
Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216
Secondary outcome [6] 0 0
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio
Timepoint [6] 0 0
Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216
Secondary outcome [7] 0 0
Percentage of Participants With a 15% or Greater Reduction in LDL-C
Timepoint [7] 0 0
Baseline and weeks 4, 6, 8, 12, 16, 20, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 168, 180, 192, 204, and 216

Eligibility
Key inclusion criteria
- Participated in Study 20110233 (NCT01588496) or another qualifying evolocumab parent protocol and have a diagnosis of familial hypercholesterolemia.

OR

* Have a diagnosis of familial hypercholesterolemia AND
* Males and females = 12 to = 80 years of age
* Stable low-fat diet and lipid-lowering therapies for at least 4 weeks
* Low-density lipoprotein cholesterol (LDL-C) >= 130 mg/dl (3.4 mmol/L) for subjects without diagnosed coronary heart disease (CHD)/CHD risk equivalent OR LDL-C >= 100 mg/dl (2.6 mmol/L) for subjects with diagnosed CHD or CHD risk equivalent OR apheresis patients have no LDL-C entry requirement
* Fasting triglycerides = 400 mg/dL(4.5 mmol/L)
* Body weight of > 40 kg or greater at screening for subjects less than 18 years of age
Minimum age
12 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* New York Heart Failure 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 screening
* Planned cardiac surgery or revascularization
* Uncontrolled cardiac arrhythmia
* Uncontrolled hypertension

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/06/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
11/05/2018
Sample size
Target
Accrual to date
Final
300
Recruitment in Australia
Recruitment state(s)
TAS,WA
Recruitment hospital [1] 0 0
Research Site - Hobart
Recruitment hospital [2] 0 0
Research Site - Perth
Recruitment postcode(s) [1] 0 0
7000 - Hobart
Recruitment postcode(s) [2] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
United States of America
State/province [3] 0 0
Ohio
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
Belgium
State/province [5] 0 0
Bruxelles
Country [6] 0 0
Belgium
State/province [6] 0 0
La Louvière
Country [7] 0 0
Brazil
State/province [7] 0 0
São Paulo
Country [8] 0 0
Canada
State/province [8] 0 0
Ontario
Country [9] 0 0
Canada
State/province [9] 0 0
Quebec
Country [10] 0 0
Czechia
State/province [10] 0 0
Brno
Country [11] 0 0
Czechia
State/province [11] 0 0
Hradec Kralove
Country [12] 0 0
Czechia
State/province [12] 0 0
Olomouc
Country [13] 0 0
Czechia
State/province [13] 0 0
Praha 2
Country [14] 0 0
Czechia
State/province [14] 0 0
Uherske Hradiste
Country [15] 0 0
France
State/province [15] 0 0
Dijon
Country [16] 0 0
France
State/province [16] 0 0
Paris Cedex 13
Country [17] 0 0
Greece
State/province [17] 0 0
Athens
Country [18] 0 0
Hong Kong
State/province [18] 0 0
New Territories
Country [19] 0 0
Israel
State/province [19] 0 0
Ramat Gan
Country [20] 0 0
Italy
State/province [20] 0 0
Cinisello Balsamo (MI)
Country [21] 0 0
Italy
State/province [21] 0 0
Napoli
Country [22] 0 0
Italy
State/province [22] 0 0
Pisa
Country [23] 0 0
Japan
State/province [23] 0 0
Ishikawa
Country [24] 0 0
Japan
State/province [24] 0 0
Osaka
Country [25] 0 0
Lebanon
State/province [25] 0 0
Beirut
Country [26] 0 0
Netherlands
State/province [26] 0 0
Amsterdam
Country [27] 0 0
Netherlands
State/province [27] 0 0
Rotterdam
Country [28] 0 0
New Zealand
State/province [28] 0 0
Christchurch
Country [29] 0 0
South Africa
State/province [29] 0 0
Gauteng
Country [30] 0 0
South Africa
State/province [30] 0 0
Western Cape
Country [31] 0 0
Spain
State/province [31] 0 0
Andalucía
Country [32] 0 0
Spain
State/province [32] 0 0
Cataluña
Country [33] 0 0
Spain
State/province [33] 0 0
Galicia
Country [34] 0 0
Spain
State/province [34] 0 0
Madrid
Country [35] 0 0
United Kingdom
State/province [35] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
A study to assess the long term safety and tolerability of evolocumab (AMG 145) in adolescents and adults with severe familial hypercholesterolemia.
Trial website
https://clinicaltrials.gov/study/NCT01624142
Trial related presentations / publications
Raal FJ, Hovingh GK, Blom D, Santos RD, Harada-Shiba M, Bruckert E, Couture P, Soran H, Watts GF, Kurtz C, Honarpour N, Tang L, Kasichayanula S, Wasserman SM, Stein EA. Long-term treatment with evolocumab added to conventional drug therapy, with or without apheresis, in patients with homozygous familial hypercholesterolaemia: an interim subset analysis of the open-label TAUSSIG study. Lancet Diabetes Endocrinol. 2017 Apr;5(4):280-290. doi: 10.1016/S2213-8587(17)30044-X. Epub 2017 Feb 16.
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.
Santos RD, Stein EA, Hovingh GK, Blom DJ, Soran H, Watts GF, Lopez JAG, Bray S, Kurtz CE, Hamer AW, Raal FJ. Long-Term Evolocumab in Patients With Familial Hypercholesterolemia. J Am Coll Cardiol. 2020 Feb 18;75(6):565-574. doi: 10.1016/j.jacc.2019.12.020.
Raal FJ, Hegele RA, Ruzza A, Lopez JAG, Bhatia AK, Wu J, Wang H, Gaudet D, Wiegman A, Wang J, Santos RD. Evolocumab Treatment in Pediatric Patients With Homozygous Familial Hypercholesterolemia: Pooled Data From Three Open-Label Studies. Arterioscler Thromb Vasc Biol. 2024 May;44(5):1156-1164. doi: 10.1161/ATVBAHA.123.320268. Epub 2024 Mar 28.
Schmidt AF, Carter JL, Pearce LS, Wilkins JT, Overington JP, Hingorani AD, Casas JP. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2020 Oct 20;10(10):CD011748. doi: 10.1002/14651858.CD011748.pub3.
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.
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01624142