Clinical trial NCT03403374: Safety and Tolerability of Repatha® (Evolocumab) in Indian Participants With Homozygous Familial Hypercholesterolemia
Official title: A Multicenter, Open-label, Single-arm, Study to Evaluate Safety and Tolerability of Repatha in Patients With Homozygous Familial Hypercholesterolemia (HoFH) in India
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Homozygous Familial Hypercholesterolemia HoFH
Keywords: Evolocumab
Hypercholesterolemia
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2018-01-18
Enrollment: 30
Sex: ALL
Minimum age (years): 12
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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:

* 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

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 12 weeks
Secondary outcomes:
measure: Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C)
timeFrame: baseline, week 12
measure: Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB)
timeFrame: baseline, week 12
measure: Percent Change From Baseline to Week 12 in Lipoprotein(a) (Lp[a])
timeFrame: baseline, week 12
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Research Site
state: Delhi
city: New Delhi
country: India
facility: Research Site
state: Delhi
city: New Delhi
country: India
facility: Research Site
state: Delhi
city: New Delhi
country: India
facility: Research Site
state: Delhi
city: Ahmedabad
country: India
facility: Research Site
state: Gujarat
city: Bangalore
country: India
facility: Research Site
state: Karnataka
city: Belagavi
country: India
facility: Research Site
state: Karnataka
city: Kochi
country: India
facility: Research Site
state: Kerala
city: Mumbai
country: India
facility: Research Site
state: Maharashtra
city: Pune
country: India
facility: Research Site
state: Maharashtra
city: Pune
country: India
facility: Research Site
state: Maharashtra
city: Lucknow
country: India
facility: Research Site
state: Uttar Pradesh
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.