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

Study Overview
=================
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.

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

Conditions
-----------------
Homozygous Familial Hypercholesterolemia HoFH

Intervention / Treatment
-----------------
* Drug: evolocumab


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Evolocumab<br>Evolocumab 420 mg subcutaneous (SC) once monthly (QM) or every 2 weeks (Q2W; for participants on apheresis). | Drug: evolocumab<br>* Administered by SC injection via autoinjector (AI)/pen<br>* Other names: EvoMab;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C) |  | baseline, week 12 | 
| Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB) |  | baseline, week 12 | 
| Percent Change From Baseline to Week 12 in Lipoprotein(a) (Lp[a]) |  | baseline, week 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Evolocumab, Hypercholesterolemia