Clinical trial NCT04034485: Phase 3 Study to Evaluate the Efficacy and Safety of LIB003 With Evolocumab in HoFH
Official title: Randomized, Open-Label, Cross-Over, Phase 3 Study to Evaluate the Efficacy and Safety of LIB003 With Evolocumab in Homozygous Familial Hypercholesterolemia Patients on Stable Lipid-Lowering Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Homozygous Familial Hypercholesterolemia
Keywords: LDL cholesterol
PCSK9 inhibition
Lead sponsor: LIB Therapeutics LLC
Sponsor class: INDUSTRY
First posted: 2019-07-26
Enrollment: 65
Sex: ALL
Minimum age (years): 10
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: open label, randomized, cross-over
Primary purpose: TREATMENT

Brief summary: To compare the safety, tolerability and LDL-C response after 24 Weeks of monthly (every 4 weeks \[Q4W\]) subcutaneous (SC) dosing of LIB003 300 mg with monthly (Q4W) SC dosing of 420 mg evolocumab (Repatha®) in patients with HoFH on stable diet and oral LDL-C-lowering drug therapy

Detailed description: Patients with verified HoFH on stable and continuing doses of oral lipid lowering therapy will be randomized to either evolocumab 420 mg Q4W or LIB003 300 mg Q4W for 24 weeks (Period A). At Week 24, subjects will be crossed over to LIB003 if they were on evolocumab and vice versa for the next 24 weeks (Period B).

Eligibility criteria: Inclusion Criteria:

* HoFH diagnosed clinically and confirmed by genotyping
* Weight of \>30 kg and body mass index (BMI) \>17 and \<40 kg/m2
* stable diet and lipid-lowering oral therapies for at least 4 weeks

Exclusion Criteria:

* mipomersen within 6 months of screening;
* LDL or plasma apheresis \<2 months prior to randomization
* history of non-response to PCSK9 mAb or presence of receptor negative/null LDLR activity expected to result in non-response to PCSK9 inhibition
* prior or active clinical condition or acute and/or unstable systemic disease compromising subject inclusion

Primary outcomes:
measure: Percent reduction in Low Density Lipoprotein Cholesterol (LDL-C) at week 24
timeFrame: baseline to 24 weeks on each treatment
Secondary outcomes:
measure: The incidence and severity of treatment emergent adverse events (TEAEs)
timeFrame: baseline to 24 weeks on each treatment
Other outcomes:
measure: Percent reduction in lipoprotein (a) [Lp(a)] at week 24
timeFrame: baseline to 24 weeks on each treatment
measure: Percent reduction in apolipoprotein B (Apo B) at week 24
timeFrame: baseline to 24 weeks on each treatment
measure: Presence of anti LIB003 antibodies (ADAs)
timeFrame: baseline to 24 weeks
Locations:
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Cincinnati
country: United States
facility: Metabolic & Atherosclerosis Research Center (MARC)
state: Ohio
city: Delhi
country: India
facility: VMMC & Safdarjung Hospital
state: NCT
city: Ahmedabad
country: India
facility: CIMS Hospital Pvt. Ltd
city: New Delhi
country: India
facility: G.B. Pant Institute of Postgraduate Medical Education & Research
city: Jerusalem
country: Israel
facility: Department of Medicine, Hadassah University Hospital
city: Petah Tikva
country: Israel
facility: Rabin Medical Center, Beilinson Hospital,
city: Oslo
country: Norway
facility: Lipid Clinic, Oslo University Hospital
city: Johannesburg
country: South Africa
facility: Carbohydrate and Lipid Metabolism Research Unit
state: Gauteng
city: Cape Town
country: South Africa
facility: Division of Lipidology, Department of Medicine University of Cape Town
state: Western Province
city: İzmir
country: Turkey
facility: Ege University Medical School
state: Bornova
city: Afyon
country: Turkey
facility: Afyonkarahisar Health Sciences University
Study officials:
affiliation: LIB Therapeutics
name: Evan A Stein, MD PhD
role: STUDY_DIRECTOR
References: