Familial Chylomicronemia Syndrome
Conditions
Brief summary
This is a randomized, double-blinded, placebo controlled, two periods phase 3 clinical study. The primary objective of the study was to evaluate the efficacy and safety of Plozasiran injection in Chinese adults with familial chylomicronemia syndrome (FCS). A total of 37 participants were enrolled in the study. The duration of the study randomized period was approximately 112 weeks, including a screening period of up to 8 weeks and a treatment period of up to 104 weeks. Participants who completed the randomized period will continue in a 1-year open-label extension period where all participants will receive Plozasiran.
Interventions
DRUGPlozasiran
Subcutaneous injection
DRUGPlacebon
Subcutaneous injection
Sponsors
Visirna Therapeutics HK Limited
Arrowhead Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males or nonpregnant (who do not plan to become pregnant), nonlactating females ≥18 years of age * Fasting triglycerides (TG) ≥10 mmol/L (\~880 mg/dL) at screening, that is refractory to standard lipid lowering therapy (sample drawn after at least the minimum time on stable lipid-lowering regimen described in protocol). Two repeat tests are allowed to qualify. * A diagnosis of FCS * Willing to follow dietary counseling as per PI judgment based on local standard of care, consistent with an intake of ≤20 g of fat per day during the study * If on medications for management of type 2 diabetes, or other medications specified in protocol, the dosing regimen must be stable before collection of qualified lipid parameter at screening. * Participants with a medical history of clinical atherosclerotic cardiovascular disease (ASCVD) or those with elevated 10-year ASCVD risk (eg, ≥7.5% per American Heart Association / American College of Cardiology risk calculator) must be on appropriate lipid-lowering therapy as per local standard of care (ie, including moderate to high intensity statin, as indicated) prior to collection of qualifying TG levels. * Participants of childbearing potential must agree to use a highly effective form of contraception in addition to a male condom, during the study and for at least 24 weeks after the last dose of investigational product (IP). Women of childbearing potential on a hormonal contraceptive must be stable on the medication for ≥1 menstrual cycles prior to Day 1. Men must not donate sperm during the study and for at least 24 weeks after the last dose of IP.
Exclusion criteria
* Current use or use within the last 365 days from Day 1 of any hepatocyte-targeted siRNA or antisense oligonucleotide molecule * Diabetes mellitus with any of the following: 1. Newly diagnosed within 12 weeks of screening 2. HbA1c ≥9.0% at screening * Active pancreatitis within 12 weeks before Day 1 * History of acute coronary syndrome event within 24 weeks of Day 1 The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Fasting Serum Triglyceride (TG) at Month 10 | Baseline to Month 10 | Blood samples for lipid parameters were collected at the specified time points. Fasting serum TG at Month 10 was defined as geometric mean of 2 measurements taken during Month 10, or the other non-missing measurement if any one of the two measurements was missing during Month 10. Analysis was performed on the basis of the handling strategy for intercurrent events, missing fasting serum was imputed mainly based on the Pattern Mixture Models (PMM). Descriptive statistics were calculated based on non-imputed data. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Fasting Serum TG at Months 10 and 12 (Averaged) | Baseline to Months 10 and 12 (averaged) | Blood samples for lipid parameters were collected at the specified time points. Fasting serum TG at Month 10 and Month 12 was defined as the geometric mean of the measurements in Month 10 and Month 12 or the non-missing measurement in the other month if measurement in any one of the two months was missing. Analysis was performed on the basis of the handling strategy for intercurrent events, missing fasting serum TG was imputed mainly based on the PMM. Descriptive statistics were calculated based on non-imputed data. |
| Percent Change From Baseline in Fasting Serum Apolipoprotein C3 (APOC3) at Month 10 | Baseline to Month 10 | Blood samples for lipid parameters were collected at the specified time points. Baseline of fasting serum APOC 3 was defined as the last non-missing value prior to or on the first dosing date. Analysis was performed on the basis of the handling strategy for intercurrent events, missing values were imputed using the PMM. Descriptive statistics were calculated based on non-imputed data. |
| Percent Change From Baseline in Fasting Serum APOC3 at Month 12 | Baseline to Month 12 | Blood samples for lipid parameters were collected at the specified time points. Baseline of fasting serum APOC 3 was defined as the last non-missing value prior to or on the first dosing date. Analysis was performed on the basis of the handling strategy for intercurrent events, missing values were imputed using the PMM. Descriptive statistics were calculated based on non-imputed data. |
| Percent Change From Baseline in Fasting Serum Non-high Density Lipoprotein Cholesterol (Non-HDL-C) and High Density Lipoprotein Cholesterol (HDL-C) at Month 10 | Baseline to Month 10 | Blood samples for lipid parameters were collected at the specified time points. Baseline was defined as the last non-missing value prior to or on the first dosing date. |
| Percent Change From Baseline in Fasting Serum TG, Non-HDL-C, and HDL-C at Month 12 | Baseline to Month 12 | Blood samples for lipid parameters were collected at the specified time points. Non-HDL-C and HDL-C baseline was defined as the last non-missing value prior to or on the first dosing date. |
| Percentage of Participants Achieving Fasting Serum TG of <500 mg/dL at Month 10 | 10 Month | Blood samples for lipid parameters were collected at the specified time points. |
| Percentage of Participants Achieving Fasting Serum TG of <500 mg/dL at Month 12 | 12 Month | Blood samples for lipid parameters were collected at the specified time points. |
| Change From Baseline at Each Scheduled Assessment in Fasting Serum TG up to Month 12 | From baseline up to Month 12, at Months 1,2,3,4,5,6,7,8,9,10,11 and 12 | Blood samples for lipid parameters were collected at the specified time points. |
| Percent Change From Baseline at Each Scheduled Assessment in Fasting Serum TG up to Month 12 | From baseline up to Month 12, at Months 1,2,3,4,5,6,7,8,9,10,11 and 12 | Blood samples for lipid parameters were collected at the specified time points. |
| Number of Participants With Positively Adjudicated Events of Acute Pancreatitis | From first administration of study treatment (Day 1) through Month 12. | Any AEs and SAEs reported by the investigator during the study that were consistent with acute pancreatitis events were adjudicated by the blinded Data Safety Committee based on the Atlanta Classification for Acute Pancreatitis 2013 for fulfillment of any 2 of the following 3 criteria: 1. Abdominal pain consistent with symptoms of acute pancreatitis (acute episodes of persistent, severe upper abdominal pain often radiating to the back) 2. Serum lipase activity (or amylase activity) ≥3 × upper limit of normal (ULN) 3. Characteristic findings of acute pancreatitis on contrast-enhanced computed tomography (CECT) or magnetic resonance imaging (MRI) or transabdominal ultrasonography |
Countries
China
Contacts
STUDY_CHAIRDong YOU, MD., PhD.
Visirna Therapeutics HK Limited
Participant flow
Recruitment details
A total of 63 participants were screened from 10-July-2023 to 19-Jan-2024, of which 26 participants were screen failures mainly due to selection criteria not met.
Pre-assignment details
A total of 37 participants were randomized and treated in this study. Participants were randomized in 1:1:1 ratio to receive Plozasiran 25 mg dose group, Plozasiran 50 mg dose group and matching placebo group.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Fasting serum TG (mg/dL) | 1786.1 mg/dL STANDARD_DEVIATION 894.04 |
| Race/Ethnicity, Customized Ethnicity Han | 11 Participants |
| Race/Ethnicity, Customized Ethnicity Others | 2 Participants |
| Race/Ethnicity, Customized Race Asian | 12 Participants |
| Race/Ethnicity, Customized Race Others | 0 Participants |
| Region of Enrollment China | 37 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 13 |
| other Total, other adverse events | 11 / 12 | 10 / 12 | 12 / 13 |
| serious Total, serious adverse events | 1 / 12 | 0 / 12 | 4 / 13 |
Outcome results
None listed