Homozygous Familial Hypercholesterolemia
Conditions
Keywords
LDL cholesterol, PCSK9 inhibition
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).
Interventions
DRUGlerodalcibep
PCSK9 inhibitor
DRUGevolocumab
PCSK9 inhibitor
Sponsors
LIB Therapeutics LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
treatment is open label but lipid results are masked to participant, investigator and sponsor
Intervention model description
open label, randomized, cross-over
Eligibility
Sex/Gender
ALL
Age
10 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent reduction in Low Density Lipoprotein Cholesterol (LDL-C) at week 24 | baseline to 24 weeks on each treatment | Change in serum LDL-C from baseline after 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The incidence and severity of treatment emergent adverse events (TEAEs) | baseline to 24 weeks on each treatment | safety and tolerability will be based on the incidence and severity of treatment emergent adverse events |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percent reduction in lipoprotein (a) [Lp(a)] at week 24 | baseline to 24 weeks on each treatment | Change in serum Lp(a) from baseline after 24 weeks |
| Percent reduction in apolipoprotein B (Apo B) at week 24 | baseline to 24 weeks on each treatment | Change in serum Apo B from baseline after 24 weeks |
| Presence of anti LIB003 antibodies (ADAs) | baseline to 24 weeks | Measurement of ADAs at baseline and various intervals |
Countries
India, Israel, Norway, South Africa, Turkey (Türkiye), United States
Outcome results
None listed