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IRCT20150303021315N32 IRCT 2024-02-01 CinnaGen company Evaluation of non-inferiority of efficacy and safety of Evolocumab (CinnaGen) versus Evolocumab (Repatha®, Amgen Inc.) A phase III, randomized, multicenter, double-blind, two-armed, parallel, active-controlled, non-inferiority clinical trial to compare efficacy and safety of Evolocumab (CinnaGen) versus Evolocumab (Repatha®, Amgen Inc.) in patients with hyperlipidemia receiving concurrent high intensity statin 2024-04-20 anticipated 250 Complete https://irct.ir/trial/74456 interventional Randomization: Randomized, Blinding: Double blinded, Placebo: Not used, Assignment: Parallel, Purpose: Treatment, Other design features: Group sample sizes of 106 and 106 achieve 80% power to detect non-inferiority using a one-sided, two-sample t-test. Efficacy of Repatha® in comparison with placebo for mean Percent change from baseline in LDL-C at week 12 in the reference study is reported 61.8. The margin of non-inferiority is 12.36%. The true difference between the means is assumed to be 0. The significance level (alpha) of the test is 0.025. The data are drawn from populations with standard deviations of 31.96. Considering a drop-out rate of about 15% total sample size required is 250 (125/125) patients, Randomization description: The randomization plan of the patients will be carried out centrally using an R-CRAN software version 4.2.1. Using permuted block randomization, blocks (length of each block is 4 or 2) will be made, for a total of 250 patients (with 1:1 allocation ratio). Once the randomization will be made, each patient will be given a code with which she/he will be identified throughout the study. The assigned code will be made up of 3 numbers (corresponding to the randomization number) and by 4 initials (corresponding to the 2 first letters of the first name, the 2 first letters of the first surname) and 2 numbers (center code). The randomization number will be assigned in a consecutive way, Blinding description: In general, both studied medications are diagnostically indistinguishable for both patients and medical staff, as they share identical physical characteristics in terms of shape, size, material, and color, rendering them visually indiscernible. The packaging for both formulations of Evolocumab is uniform to eliminate visual distinctions. Additionally, appropriate research labels are designed for the boxes and syringes of the studied medications, adhering to EMEA regulations. Both the brand and factory-produced medications are reliably manufactured and packaged in an identical manner. Specific coding on the medication labels links each medication to the respective patient, keeping patients, medical staff, and other personnel unaware of the type of administered medication. Information regarding patient groups and the type of medication administered is not disclosed to researchers, and sealed, Decoding packets are maintained securely by CRO representative. Furthermore, individuals conducting result preparation and data analyses remain unaware of patient group classifications. 3 Hyperlipidemia. Intervention 1: Intervention group: Evolocumab (Produced by CinnaGen Co.), 140 mg every two weeks, sub cutaneous (SC), up to maximum 10 weeks (6 interventions). Intervention 2: Control group: Repatha® (Produced by CinnaGen Co.), 140 mg every two weeks, SC, up to maximum 10 weeks (6 interventions). Undecided - It is not yet known if there will be a plan to make this available Justification or reason for indecision in sharing IPD is It will be considered.
public Dr. Hamidreza Kafi
No 42, Attar St., Vanak Sq,
Tehran Iran (Islamic Republic of) 1994766411 +98 21 4347 3000 Kafi.H@orchidpharmed.com Zist Orchid Pharmed Co. scientific Dr. Seyed Hashem Sezavar Seyedi Jandaghi
No.52, Darya Crossroad, Farahzadi Blvd, Shahrak-e Gharb
Tehran Iran (Islamic Republic of) ۱۴۶۸۹۹۳۸۸۷ +98 21 2237 7530 Sezavar.sh@iums.ac.ir Iran University of Medical Sciences Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Iran (Islamic Republic of) Male or female ≥18 to ≤75 years of age Willingness for signing and having signed the informed consent form Should have received an approved high intensity statin at a stable daily dose, at least 4 weeks before screening, and has not achieved the target LDL-C level Having Established Atherosclerotic Cardiovascular Disease (ASCVD) (secondary prevention) or patients without established ASCVD (primary prevention) who are categorized as “very high risk” in ASCVD risk assessment according to AACE/ACE 2020 guideline ASCVD is defined as diagnosis of myocardial infarction, diagnosis of non-hemorrhagic stroke (TIA does not qualify as stroke for inclusion), symptomatic peripheral arterial disease (PAD), as evidenced by intermittent claudication with ankle-brachial index (ABI) greater than 0.85, or peripheral arterial revascularization procedure, or amputation due to atherosclerotic disease.- ”Very high risk” in ASCVD risk assessment is defined as followed:• Diabetes with at least 1 risk factor(s)• CKD greater than or equal to 3 with albuminuria (assessed by urine albumin/urine creatinine ratio) • HeFH Fasting LDL-C as determined by the central laboratory at screening equal or greater than 70 milligram per deciliter Fasting triglycerides less than or equal to 400 milligram per deciliter 18 years 75 years Both New York Heart Association (NYHA) III or IV heart failure or LVEF less than 30% Uncontrolled hypertension (SBP more than 180 mmHg or DBP>110 mm Hg) Type 1 diabetes, newly diagnosed or poorly controlled type 2 diabetes (HbA1c more than 8.5%) Active pancreatitis Uncontrolled serious cardiac arrhythmia less or equal to 3 months prior to randomization History of myocardial infarction/unstable angina, PCI (percutaneous coronary intervention), CABG, or stroke less or equal 3 months prior to randomization Have inadequate organ and marrow function as indicated by laboratory values:• TSH less than LLN or TSH more than1.5×ULN (in addition to abnormal free T4)• eGFR<30 mL/min/1.73m2• AST or ALT more than 3×ULN• CK more than 5×ULN Active infection Hepatitis C infection History of deep vein thrombosis or pulmonary embolism less or equal 3 months prior to randomization Administration of bile acid-sequestering resins, statins (outside of study regimen), ezetimibe, fibrates, less than 200 mg/day niacin, or more than 1000 milligram/day omega-3 fatty acids less or equal to 6 weeks prior to randomization Administration of cyclosporine, systemic steroids, vitamin A derivatives and retinol derivatives for the treatment of dermatologic conditions (except for the purpose of supplementation) less than 3 months prior to randomization Prohibited procedures such as cardiac surgery or revascularization, any weight loss procedure (e.g., bariatric surgery) within 3 months prior to randomization, or receiving any major organ transplant (e.g., lung, liver, heart, bone marrow and renal), LDL or plasma apheresis within 12 months prior to randomization Personal or family history of hereditary muscular disorders Major hematologic, metabolic, or GI disruption A female subject who is pregnant or breast feeding, or planning to become pregnant while enrolled in the study Previously received Evolocumab or any other investigational therapy to inhibit PCSK9 On a dietary regimen which is significantly deviated from recommended diet by physician (e.g., high levels of carbohydrates or lipids, low fiber regimens, or regular alcohol consumption) Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. E78.5 Hyperlipidemia, unspecified Treatment - Drugs Treatment - Drugs Intervention group: Evolocumab (Produced by CinnaGen Co.), 140 mg every two weeks, sub cutaneous (SC), up to maximum 10 weeks (6 interventions) Control group: Repatha® (Produced by CinnaGen Co.), 140 mg every two weeks, SC, up to maximum 10 weeks (6 interventions) Outcome title: Percent change of LDL-C; This outcome is expressed in percentage (%) and is calculated from baseline to week 12, depicting the the percent change in LDL-C from study initiation to the end of the week 12. Timepoint: Baseline, week 12. Method of measurement: Blood Biochemical Test. Outcome title: Percent change of LDL-C; Relevant description: this outcome is expressed as a percentage (%) and it's calculation depends on week 10 and week 12 results. Initially, the mean LDL-C at weeks 10 and 12 will be calculated followed by the calculation of the percent change relative to the baseline. subsequently, a comparison will be made between the two groups. Timepoint: Baseline, week 10, week 12. Method of measurement: Blood Biochemical Test. Outcome title: LDL-C Mean value change; Relevant description: this outcome is expressed as a value and it's calculation depends on week 10 and week 12 results. Initially, the mean LDL-C at weeks 10 and 12 will be calculated followed by the calculation of the change of the value relative to the baseline. subsequently, a comparison will be made between the two groups. Timepoint: Baseline, week 10, week 12. Method of measurement: Blood Biochemical Test. Outcome title: LDL-C Value change; Relevant description: this outcome is expressed as a value and it's calculation depends on week 12 result. The change of the LDL-C value at 12th week relative to the baseline will be calculated. subsequently, a comparison will be made between the mean values of two groups. Timepoint: Baseline, week 12. Method of measurement: Blood Biochemical Test. Percent change from baseline in triglycerides. Timepoint: Baseline, week 12. Method of measurement: Blood Biochemical Test. Percent change from baseline in HDL-C. Timepoint: Baseline, week 12. Method of measurement: Blood Biochemical Test. Percent change from baseline in total cholesterol at week 12. Timepoint: Baseline, week 12. Method of measurement: Blood Biochemical Test. Adverse events frequency. Timepoint: Baseline and weeks 0, 2, 4, 6, 8, 10 and 12. Method of measurement: Clinical monitoring. Immunogenicity: Anti-drug antibody. Timepoint: Baseline, week 12. Method of measurement: Enzyme-Linked Immunosorbent assay (ELISA). Safety of laboratory tests. Timepoint: Baseline, week 12. Method of measurement: Blood Biochemical Test. Safety of vital sign. Timepoint: Baseline, weeks 4, 8 and 12. Method of measurement: Clinical monitoring. CinnaGen company Approved 2023-12-13 Iran University of Medical Sciences Ethics Committee Iran University of Medical Sciences, Shahid Hemmat Highway Tehran Tehran Iran (Islamic Republic of)