CClinicalTrials.gg
CompletedNCT03403374RAMANUpdated May 29, 2024Results posted

Safety and Tolerability of Repatha® (Evolocumab) in Indian Participants With Homozygous Familial Hypercholesterolemia

A Phase 4 interventional study of evolocumab in Homozygous Familial Hypercholesterolemia HoFH, sponsored by Amgen. Completed at 12 sites in India. Open to participants aged 12 Years to 80 Years. Per ClinicalTrials.gov, last updated 2024-05-29.

Sponsored by Amgen · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
30
Allocation
Not applicable
Ages
12 Years to 80 Years
Sex
All
01

Study summary

To describe the safety and tolerability of evolocumab in participants with homozygous familial hypercholesterolemia (HoFH) in India. All participants will receive evolocumab over an 8-week period.

Read the detailed description

An open-label, multicentre, phase 4 study to describe the safety and tolerability of evolocumab in 30 Indian participants with HoFH. Subjects who meet the inclusion/exclusion criteria and laboratory assessments at screening will be enrolled and will be required to maintain their current lipid-lowering drug therapy throughout the duration of the trial. Participants will receive evolocumab 420 mg subcutaneous (SC) once monthly (QM) and study visits will occur approximately every 4 weeks. Apheresis participants will receive evolocumab 420 mg SC every 2 weeks to correspond with their apheresis schedule. Final administration of evolocumab (for all participants) will occur at week 8. The end of study (EOS) visit will occur at week 12 for all participants.

02

Conditions studied

  • Homozygous Familial Hypercholesterolemia HoFH

Keywords

  • Evolocumab
  • Hypercholesterolemia
03

Who can participate

Ages eligible
12 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Male or female ≥ 12 to ≤ 80 years of age at the time of signing the informed consent
  • Diagnosis of HoFH based on low-density lipoprotein cholesterol (LDL-C), familial history and xanthoma
  • On a low-fat diet and receiving background lipid-lowering therapy stable for 4 weeks prior to screening and during the time frame of the trial
  • Fasting LDL-C at screening > 130 mg/dL (3.4 mmol/L)
  • Fasting triglycerides at screening ≤ 400 mg/dL (4.5 mmol/L)

Exclusion criteria

Exclusion Criteria:

  • Use of mipomersen or lomitapide within 6 months of screening.
  • Known active infection or major hematologic, renal, metabolic, gastrointestinal, hepatic, or endocrine dysfunction
  • Currently receiving treatment in another investigational device or drug study, or less than 30 days since ending treatment on another investigational device or drug study(ies)
  • Female subject is pregnant or breastfeeding or planning to become pregnant or breastfeed
  • Female subjects of childbearing potential unwilling to use an acceptable method of effective contraception
  • Subject has known sensitivity to any of the products to be administered during dosing
  • History or evidence of any other clinically significant disorder, condition or disease
  • Subject has previously received evolocumab or any other proprotein convertase subtilisin/kexin type 9 (PKSK-9)-inhibiting therapy
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
30 participants (actual)

Study arms

  • Experimental
    Evolocumab

    Evolocumab 420 mg subcutaneous (SC) once monthly (QM) or every 2 weeks (Q2W; for participants on apheresis).

    Drug: evolocumab

Interventions

  • Drugevolocumab

    Administered by SC injection via autoinjector (AI)/pen

    Also known as: Repatha®, EvoMab

05

What researchers measure

Primary outcomes

  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    Includes both serious and non-serious adverse events (AEs). AE: any untoward medical occurrence in a participant. SAE: an AE that meets 1 on the following serious criteria: fatal; life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. TEAE: any AE starting on or after the first dose of study drug and up to and including 30 days after the end of study drug or the end of study date, whichever is earlier.

    Time frame: 12 weeks

Secondary outcomes

  1. Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C)

    Time frame: baseline, week 12

  2. Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB)

    Time frame: baseline, week 12

  3. Percent Change From Baseline to Week 12 in Lipoprotein(a) (Lp[a])

    Time frame: baseline, week 12

06

Results

Posted Nov 3, 2020

Participant flow

Participants were enrolled at 10 study centers in India. The first participant was enrolled on 04 August 2018 and the last participant was enrolled on 29 August 2019.

Participant flow — Overall Study
MilestoneEvolocumab
Started30
Completed29
Not completed1
Withdrew: Lost to follow-up1

Outcome measures

PrimaryNumber of Participants With Treatment-Emergent Adverse Events (TEAEs)

Includes both serious and non-serious adverse events (AEs). AE: any untoward medical occurrence in a participant. SAE: an AE that meets 1 on the following serious criteria: fatal; life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event. TEAE: any AE starting on or after the first dose of study drug and up to and including 30 days after the end of study drug or the end of study date, whichever is earlier.

Time frame:
12 weeks
Reported as:
Count of participants · Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
ParticipantsEvolocumab
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)10
SecondaryPercent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C)
Time frame:
baseline, week 12
Reported as:
Mean · percent change
Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C)
percent changeEvolocumab
Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C)-6.4 ± 22.7
SecondaryPercent Change From Baseline to Week 12 in Apolipoprotein B (ApoB)
Time frame:
baseline, week 12
Reported as:
Mean · percent change
Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB)
percent changeEvolocumab
Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB)-6.0 ± 19.8
SecondaryPercent Change From Baseline to Week 12 in Lipoprotein(a) (Lp[a])
Time frame:
baseline, week 12
Reported as:
Mean · percent change
Percent Change From Baseline to Week 12 in Lipoprotein(a) (Lp[a])
percent changeEvolocumab
Percent Change From Baseline to Week 12 in Lipoprotein(a) (Lp[a])-0.2 ± 26.2

Adverse events

Collected over All-cause mortality: from enrollment (up to 4 weeks prior to treatment) through end of study (week 12). Serious and other adverse events: from the first dose of study treatment through end of treatment (at week 8) plus 4 weeks (week 12).. Non-serious events are listed at a 2% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Evolocumab0/30 (0%)2/30 (6.7%)8/30 (26.7%)
Most frequent serious events
Most frequent serious events
EventEvolocumab
Coronary artery diseaseCardiac disorders1/30
SyncopeNervous system disorders1/30
Most frequent other events
Showing 10 of 12
Most frequent other events
EventEvolocumab
Angina pectorisCardiac disorders1/30
Injection site painGeneral disorders1/30
Injection site swellingGeneral disorders1/30
Peripheral swellingGeneral disorders1/30
PyodermaInfections and infestations1/30
VaricellaInfections and infestations1/30
ArthralgiaMusculoskeletal and connective tissue disorders1/30
ArthritisMusculoskeletal and connective tissue disorders1/30
CoughRespiratory, thoracic and mediastinal disorders1/30
Diabetic woundSkin and subcutaneous tissue disorders1/30

Baseline characteristics

Age, Continuous
Age, Continuous(years)Evolocumab
Mean23.2 ± 13.1
Age, Customized
Age, Customized(Participants)Evolocumab
Adolescents (12 - 17 years old)13
Adults (18 - 64 years old)16
Adults (65 - 84 years old)1
Sex: Female, Male
Sex: Female, Male(Participants)Evolocumab
Female13
Male17
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Evolocumab
Hispanic or Latino0
Not Hispanic or Latino30
Unknown or Not Reported0
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Evolocumab
Asian30
Low-Density Lipoprotein Cholesterol (LDL-C)
Low-Density Lipoprotein Cholesterol (LDL-C)(mg/dL)Evolocumab
Mean473.5 ± 135.2
Apolipoprotein B (ApoB)
Apolipoprotein B (ApoB)(mg/dL)Evolocumab
Mean275.3 ± 69.1
Lipoprotein(a) (Lp[a])
Lipoprotein(a) (Lp[a])(nmol/L)Evolocumab
Mean201.3 ± 177.6
07

Study locations

12 sites
  • Research Site
    New Delhi, Delhi 110 002, India
  • Research Site
    New Delhi, Delhi 110 029, India
  • Research Site
    New Delhi, Delhi 110 060, India
  • Research Site
    New Delhi, Delhi 110 062, India
  • Research Site
    Ahmedabad, Gujarat 380 054, India
  • Research Site
    Bangalore, Karnataka 560 017, India
  • Research Site
    Belagavi, Karnataka 590010, India
  • Research Site
    Kochi, Kerala 682 027, India
  • Research Site
    Mumbai, Maharashtra 400 007, India
  • Research Site
    Pune, Maharashtra 411 005, India
  • Research Site
    Pune, Maharashtra 411 006, India
  • Research Site
    Lucknow, Uttar Pradesh 226 003, India
08

References and documents

Publications

  • 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. PubMed 38545781 ↗
  • Bansal S, Ruzza A, Sawhney J, Kulkarni G, Iyengar S, Mehta V, Hamer A, Wu Y, Raal FJ. Evolocumab in patients with homozygous familial hypercholesterolemia in India. J Clin Lipidol. 2021 Nov-Dec;15(6):814-821. doi: 10.1016/j.jacl.2021.10.003. Epub 2021 Oct 20. PubMed 34750081 ↗

Study documents

  • Study protocol · Aug 16, 2017
  • Statistical analysis plan · Mar 9, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Supporting information: Study protocol, Sap, Icf, Csr

09

Registry details

Key details

Study ID
NCT03403374
Lead sponsor
Amgen
Responsible party
Sponsor
First posted
Jan 18, 2018
Start date
Aug 4, 2018
Primary completion
Nov 27, 2019
Completion
Nov 27, 2019
Results posted
Nov 3, 2020
Last update
May 29, 2024

Study contacts

MD
study director · Amgen

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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