Homozygous Familial Hypercholesterolemia HoFH
Conditions
Keywords
Evolocumab, Hypercholesterolemia
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.
Interventions
DRUGevolocumab
Administered by SC injection via autoinjector (AI)/pen
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 80 Years
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
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 12 weeks | 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. |
Secondary
| Measure | 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 |
Countries
India
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Evolocumab Evolocumab 420 mg subcutaneous (SC) once monthly (QM) or every 2 weeks (Q2W; for participants on apheresis). | 30 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Evolocumab |
|---|---|
| Age, Continuous | 23.2 years STANDARD_DEVIATION 13.1 |
| Age, Customized Adolescents (12 - 17 years old) | 13 Participants |
| Age, Customized Adults (18 - 64 years old) | 16 Participants |
| Age, Customized Adults (65 - 84 years old) | 1 Participants |
| Apolipoprotein B (ApoB) | 275.3 mg/dL STANDARD_DEVIATION 69.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Lipoprotein(a) (Lp[a]) | 201.3 nmol/L STANDARD_DEVIATION 177.6 |
| Low-Density Lipoprotein Cholesterol (LDL-C) | 473.5 mg/dL STANDARD_DEVIATION 135.2 |
| Race/Ethnicity, Customized Asian | 30 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 30 |
| other Total, other adverse events | 8 / 30 |
| serious Total, serious adverse events | 2 / 30 |
Outcome results
Primary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Evolocumab | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | 10 Participants |
Secondary
Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB)
Time frame: baseline, week 12
Population: Participants with a baseline and week 12 assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Evolocumab | Percent Change From Baseline to Week 12 in Apolipoprotein B (ApoB) | -6.0 percent change | Standard Deviation 19.8 |
Secondary
Percent Change From Baseline to Week 12 in Lipoprotein(a) (Lp[a])
Time frame: baseline, week 12
Population: Participants with a baseline and week 12 assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Evolocumab | Percent Change From Baseline to Week 12 in Lipoprotein(a) (Lp[a]) | -0.2 percent change | Standard Deviation 26.2 |
Secondary
Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C)
Time frame: baseline, week 12
Population: Participants with a baseline and week 12 assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Evolocumab | Percent Change From Baseline to Week 12 in Low-Density Lipoprotein Cholesterol (LDL-C) | -6.4 percent change | Standard Deviation 22.7 |