araag2/TREC_Precision-Medicine huggingface dataset:
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Evaluation of the Efficacy and Safety of Bempedoic Acid (ETC-1002) 180mg When Added to PCSK9 Inhibitor Therapy

Summary: The purpose of this study is to determine if bempedoic acid (ETC-1002) 180mg added to PCSK9 inhibitor (evolocumab) therapy is effective and safe in patients with elevated LDL cholesterol.


Eligibility: Inclusion Criteria:
  -  Age ≥18 years or legal age of majority depending on regional law
  -  Fasting, calculated LDL-C at screening ≥160 mg/dL
  -  Men and nonpregnant, nonlactating women
  Exclusion Criteria:
  -  Heterozygous (HeFH) or Homozygous (HoFH) Familial Hypercholesterolemia
  -  Total fasting TG ≥500 mg/dL
  -  Renal dysfunction or a glomerulonephropathy; eGFR <30 mL/min/1.73 m2
  -  Known cardiovascular disease (CVD), peripheral arterial disease (PAD), or cerebrovascular disease (CD)
  -  History of type 1 or type 2 diabetes
  -  Uncontrolled hypertension
  -  Uncontrolled hypothyroidism
  -  Liver disease or dysfunction
  -  Gastrointestinal conditions or procedures (including Lap-Band® or gastric bypass)
  -  History of hematologic or coagulation disorders
  -  History of malignancy (except non-metastatic basal or squamous cell carcinoma of the skin and cervical carcinoma in situ)
  -  Unexplained creatine kinase (CK) >3 × ULN
  -  Use of a cholesterylester transfer protein (CETP) inhibitor in the last 12 months prior to screening, such as: anacetrapib, dalcetrapib, or evacetrapib
  -  Pregnant or breast feeding, or planning to become pregnant during treatment and/ or within 30 days after the end of treatment

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: IN-TANDEM Familial Hypercholesterolemia Pilot Study

Summary: The purpose of this study is to validate the use of the FH Foundation FIND FH® Algorithm as a clinical decision support tool. FIND FH (Flag/Identify/Network/Engage) is a national initiative that utilizes machine learning and data mining techniques to identify individuals whose profiles are consistent with FH patients. The algorithm will be tested in adults with at least one cardiovascular comorbidity. Study subjects will be asked to provide either a saliva, buccal or venous blood sample for DNA and biomarker analysis


Eligibility: Inclusion Criteria:
  -  Age 18 years or older
  -  At least one cardiovascular co-morbidity or receiving treatment for a cardiovascular comorbidity
  -  Algorithm score 0-1
  -  Most recent encounter with a provider within five years of query date
  Exclusion Criteria:
  -  Any medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study, or confound study data

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Impact of LDL-cholesterol Lowering on Platelet Activation

Summary: The primary goal is to assess the impact of Evolocumab therapy on platelet function of familial hypercholesterolemia (FH) patients in a randomized, double blind study. Evolocumab is a humanized monoclonal antibody that targets circulating PCSK9, increases hepatic LDL receptor, decreases plasma LDL cholesterol and reduces risk of cardiovascular events. Evolocumab (brand name Rapatha) has been approved by FDA along with diet and maximally tolerated statin therapy in adults with FH or atherosclerotic heart or blood vessel problems, who need additional lowering of LDL cholesterol.
  The secondary goal is to determine if platelet activation or the response to Evolocumab therapy is modified by rs3184504 polymorphism. The investigators believe that these investigations will complement ongoing studies to demonstrate that Evolocumab reduces athero-thrombotic risk and aid the decision-making as to whether Evolocumab can reduce the atherothrombotic risk in ACS patients.

Detailed description: Hyperlipidemia as exemplified by familial hypercholesterolemia is associated with increased platelet activation and an underlying pro-coagulant state. Hyperlipidemia primes platelets and increases platelet activation in response to various agonists. Plasma cholesterol levels appear to have a critical role in modulating platelet activity as hypercholesterolemia increases platelet activation more potently than hypertriglyceridemia. Increased platelet reactivity may contribute to the increased risk of atherothrombosis associated with hypercholesterolemia. Plasma levels of platelet activation markers such as thrombin-antithrombin complex (TAT), soluble P-selectin (sP-selectin), soluble CD40L (sCD40L) or P-selectin exposure at surface of platelets are increased in hypercholesterolemic patients. Increased levels of the platelet activation markers are associated with increased platelet membrane cholesterol content in hypercholesterolemia.Statins may show antithrombotic properties.

Eligibility: Inclusion Criteria:
  -  Subjects who have a clinical diagnosis of familial hypercholesterolemia (FH)
  -  Subjects who are referred to Dr. Ginsberg's Lipid Practice for treatment with PCSK9 inhibitor
  -  Subjects with LDL cholesterol levels >100 mg/dl on baseline treatment with statins and/or ezitimibe
  Exclusion Criteria:
  -  Children under 18 years of age

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Trial to Evaluate the Effect of Inclisiran Treatment on Low Density Lipoprotein Cholesterol (LDL-C) in Subjects With Heterozygous Familial Hypercholesterolemia (HeFH)

Summary: This is a Phase III, placebo-controlled, double-blind, randomized study in participants with HeFH and elevated LDL-C to evaluate the efficacy, safety, and tolerability of subcutaneous (SC) injection(s) of inclisiran. The study will be multicenter and international.


Eligibility: Inclusion Criteria:
  Participants may be included if they meet all of the following inclusion criteria prior to randomization:
  1. Male or female participants ≥18 years of age.
  2. History of HeFH with a diagnosis of HeFH by genetic testing; and/or a documented history of untreated LDL-C of >190 mg/dL, and a family history of familial hypercholesterolemia, elevated cholesterol or early heart disease that may indicate familial hypercholesterolemia.
  3. Serum LDL-C ≥2.6 millimoles (mmol)/liter (L) (≥100 mg/dL) at screening.
  4. Fasting triglyceride <4.52 mmol/L (<400 mg/dL) at screening.
  5. Participants on statins should be receiving a maximally tolerated dose.
  6. Participants not receiving statins must have documented evidence of intolerance to all doses of at least 2 different statins.
  7. Participants on lipid-lowering therapies (such as a statin and/or ezetimibe) should be on a stable dose for ≥30 days before screening with no planned medication or dose change during study participation.
  Exclusion Criteria:
  Participants will be excluded from the study if any of the following exclusion criteria apply immediately prior to randomization:
  1. New York Heart Association (NYHA) class IV heart failure.
  2. Uncontrolled cardiac arrhythmia
  3. Uncontrolled severe hypertension
  4. Active liver disease
  5. Females who are pregnant or nursing, or who are of childbearing potential and unwilling to use at least 2 methods of highly effective contraception (failure rate less than 1% per year) (combined oral contraceptives, barrier methods, approved contraceptive implant, long-term injectable contraception, or intrauterine device) for the entire duration of the study. Exemptions from this criterion:
  1. Women >2 years postmenopausal (defined as 1 year or longer since last menstrual period) AND more than 55 years of age.
  2. Postmenopausal women (as defined above) and less than 55 years of age with a negative pregnancy test within 24 hours of randomization.
  3. Women who are surgically sterilized at least 3 months prior to enrollment.
  6. Males who are unwilling to use an acceptable method of birth control during the entire study period (condom with spermicide).
  7. Treatment with other investigational products or devices within 30 days or 5 half-lives of the screening visit, whichever is longer.
  8. Treatment (within 90 days of screening) with monoclonal antibodies directed towards PCSK9.
  The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Safety and Tolerability of Repatha in Indian Subjects With Homozygous Familial Hypercholesterolemia

Summary: To describe the safety and tolerability of Repatha in subjects with homozygous familial hypercholesterolemia (HoFH) in India. All subjects will receive Repatha over an 8 week period.

Detailed description: An open-label, multicentre, phase 4 study to describe the safety and tolerability of Repatha in 30 Indian subjects 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. Subjects will receive Repatha 420 mg QM SC and study visits will occur approximately every 4 weeks. Apheresis subjects will receive Repatha 420 mg SC every 2 weeks to correspond with their apheresis schedule. Final administration of Repatha (for all subjects) will occur at week 8. The end of study (EOS) visit will occur at week 12 for all subjects.

Eligibility: Inclusion Criteria:
  -  Male or female ≥ 12 to ≤ 80 years of age at the time of signing the informed consent.
  -  Diagnosis of HoFH based on 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 PCSK9-inhibiting therapy.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Evaluate the Long-Term Safety and Efficacy of Evinacumab in Patients With Homozygous Familial Hypercholesterolemia

Summary: The primary objective of the study is to evaluate the long-term safety and tolerability of evinacumab in patients with Homozygous Familial Hypercholesterolemia (HoFH). The secondary objectives of the study are to evaluate the effect of evinacumab on lipid parameters in patients with HoFH and to evaluate the potential development of anti-evinacumab antibodies.


Eligibility: Key Inclusion Criteria:
  1. Completion of the parent study in which they participated
  2. Able to understand and complete study-related questionnaires
  Key Exclusion Criteria:
  1. Significant protocol deviation in the parent study based on the investigator's judgment, such as non-compliance by the patient
  2. Concomitant medications that have not been stable prior to the baseline visit
  3. Adverse event leading to permanent discontinuation from parent study
  4. Any new condition or worsening of an existing condition, which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in or completing the study
  5. Member of the clinical site study team and/or his/her immediate family
  6. Pregnant or breastfeeding women
  7. Women of childbearing potential who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 24 weeks after the last dose of study drug
  8. Sexually active men who are unwilling to use forms of medically acceptable birth control during the study drug treatment period and for 24 weeks after the last injection of study drug
  Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Usability Study of the Commercial Auto-injector Device and the New Auto-injector Device (SYDNEY) in Patients With High or Very High CV Risk With Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy

Summary: Primary Objective:
  To collect real-use (usability) data assessing the robustness and user interaction of the new alirocumab auto-injector device (which is referred to as SYDNEY), in unsupervised settings.
  Secondary Objective:
  Device-related:
  -  To collect real-use (usability) data assessing the robustness and user interaction of SYDNEY and the current alirocumab auto-injector device (which is referred to as AI) in supervised settings.
  Pharmacokinetics:
  -  To compare alirocumab pharmacokinetics (PK) administered using SYDNEY and AI.
  -  To evaluate alirocumab PK administered using SYDNEY.
  Anti-drug antibodies:
  -  To evaluate the development of anti-drug (alirocumab) antibodies (ADA).
  Efficacy/pharmacodynamics:
  -  To compare the percent and absolute change in low-density lipoprotein cholesterol (LDL-C) using SYDNEY and AI.
  -  To evaluate the percent and absolute change in LDL-C using SYDNEY.
  Safety:
  -  To evaluate the safety and tolerability of alirocumab using both SYDNEY and AI.

Detailed description: Total study duration per patient is expected to be up to 18 weeks, with up to 2 weeks of screening period and 16 weeks of study treatment period.

Eligibility: Inclusion criteria :
  -  Patients are in either category A or B (below), and are not adequately controlled with a stable daily dose of atorvastatin (20 mg or 40 mg), or rosuvastatin (10 mg or 20 mg) for at least 4 weeks prior to the screening visit (Week -2), with or without other lipid-modifying therapy (LMT):
  -  A. Patients with heterozygous familial hypercholesterolemia (heFH) (diagnosis based on either genotyping or clinical criteria) OR
  -  B. Non-FH patients at high or very high cardiovascular (CV) risk. High and very high cardiovascular risk patients include patients with coronary heart disease (CHD), non-CHD cardiovascular disease (CVD), and other risk factors.
  -  Patient willing and able to self-inject for the duration of the study.
  Exclusion criteria:
  -  Low-density lipoprotein cholesterol (LDL-C) <70 mg/dL (<1.81 mmol/L) at the screening visit.
  -  Currently taking a daily dose of statin that is not atorvastatin 20 mg or 40 mg, or rosuvastatin 10 mg or 20 mg.
  -  Not on a stable dose of LMT (including statin) for at least 4 weeks, prior to the screening visit and from screening to randomization.
  -  Having previously used any device for the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor administration, or having participated in any clinical trial for a PCSK9 inhibitor.
  -  Fasting serum Triglyceride (TG) >400 mg/dL (>4.52 mmol/L) at the screening visit.
  The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: A First In Human Study to Assess CiVi007 in Subjects With an Elevated LDL-Cholesterol Level

Summary: The primary objective of the study is to assess pharmacokinetics, dynamics, safety and tolerability of CiVi007 following single and multiple subcutaneous doses in subjects, including those on statin therapy


Eligibility: Key Inclusion Criteria:
  -  Males or females, of any race, with fasting LDL C >2.6 mmol/L (100 mg/dL) and fasting serum triglycerides <4.52 mmol/L (400 mg/dL)
  -  haematology and clinical chemistry without clinically significant abnormal values
  -  Normal renal and hepatic function
  -  Women must not be pregnant, lactating or of child bearing potential
  -  Men must be willing to use appropriate contraception during the study
  -  Able to comprehend and willing to sign an ICF and to abide by the study restrictions.
  Key Exclusion Criteria:
  -  Any uncontrolled or serious disease, or any medical or surgical condition
  -  History or presence of coronary heart disease, peripheral artery disease, or cerebrovascular disease
  -  Uncontrolled hypertension
  -  Insulin dependent diabetes mellitus
  -  Secondary dyslipidemia
  -  History of renal or hepatic diseases, acquired immune deficiency syndrome, positive human immunodeficiency virus test and/or history of viral hepatitis B or C
  -  History of cancer within 5 years
  -  History of high alcohol consumption or positive alcohol breath test or urinary test for drugs of abuse
  -  Participation in another clinical study within 3 months prior to screening or participation in another study
  -  Use of treatment (e.g. antibody) towards PCSK9
  -  History of multiple drug allergies or intolerance to subcutaneous injection.

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Evolocumab Versus LDL Apheresis in Patients With Hypercholesterolemia

Summary: An open-label, prospective phase III study to compare the efficacy and safety of administering evolocumab versus treatment with LDLapheresis in patients with familial hypercholesterolemia and high cardiovascular risk.

Detailed description: STUDY DESIGN An open-label, prospective phase III study to compare the efficacy and safety of administering evolocumab versus treatment with LDLapheresis in patients with familial hypercholesterolemia and high cardiovascular risk.
  STUDY POPULATION The chosen population is constituted by patients belonging to the LDL-apheresis program of the General University Hospital Gregorio Marañón with the diagnosis of familial hypercholesterolemia and a history of cardiovascular disease.
  Number of patients expected to participate in the study according to the base of patients treated with LDL-apheresis: 10.
  STUDY DESIGN:
  Non-controlled intervention study to evaluate the different therapies in the treatment of hypercholesterolemia, in which each patient will be self-controlled. The variables will be analyzed during different phases
  1. LDL-apheresis phase: Retrospectively during the previous year, pre- and postapheresis variables will be collected from the following lipid parameters: total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, atherogenicity index, Lipoprotein A, apo-A, apo- B; inflammatory parameters: PCR, ferritin, fibrinogen, leukocytes and polymorphonuclear and immunological parameters: immunoglobulins and complement.
  2. Evolocumab phase: LDL-apheresis will be suspended for three months and Evolocumab administered: 140 mg / 15 days subcutaneously. The same parameters indicated in the previous section will be measured every two weeks.
  3. Combined phase: During the following three months evolocumab will continue to be administered biweekly and the LDL-apheresis procedure will be spaced from biweekly to monthly, the same analytical parameters being measured again every two weeks.

Eligibility: Inclusion Criteria:
  -  patients with age> 18 years
  -  hypercholesterolemia with LDL-cholesterol> 100 mg / dl in treatment with the maximum dose tolerated by statins and a history of severe cardiovascular disease
  -  patients who are included in the LDL-apheresis / biweekly program
  Exclusion Criteria:
  -  contraindications to receive evolocumab according to technical data.
  -  hospital admission of any cause in the last three months prior to the inclusion of the study
  -  cardiovascular event in the three months prior to the inclusion of the study
  -  Inability to sign informed consent
  -  pregnant women and non-menopausal women who do not use at least one adequate contraceptive method

Relevance to patient case: not relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Safety and Efficacy Following Repeat-Dose of Evinacumab (Anti-ANGPTL3) in Patients With Severe Hypertriglyceridemia (sHTG) at Risk for Acute Pancreatitis

Summary: The primary objective is to determine the change in Triglyceride (TG) levels following 12 weeks of repeated Intravenous (IV) doses of evinacumab.


Eligibility: Key Inclusion Criteria:
  1. Previous documentation in the patient's medical records of a fasting serum TG measurement ≥ 1000 mg/dL (11.3 mmol/L) on more than 1 occasion, and all fasting TG values ≥500 mg/dL (5.6 mmol/L) at screening
  2. History of a hospitalization and diagnosis of acute pancreatitis in the past 10 years
  3. On stable lipid-modifying diet with or without medications (eg, statins, niacin, omega-3 fatty acids). Lipid-modifying diet and doses of medications should be stable for at least 4 weeks (6 weeks for fibrates, 8 weeks for PCSK9 inhibitors) prior to screening
  4. Body mass index (BMI) of 18-40 kg/m2
  Key Exclusion Criteria:
  1. A hospital or clinic discharge diagnosis of acute pancreatitis within 12 weeks of screening
  2. Lipid apheresis or plasma exchange treatment within the last 4 weeks or plans to undergo apheresis or plasma exchange during the time frame of the study
  3. History of class 3/4 heart failure at any time in the past, or hospitalization for heart failure, diagnosis of a myocardial infarction, stroke, Transient ischemic attack (TIA), unstable angina, Coronary artery bypass surgery (CABG), Percutaneous coronary intervention (PCI), carotid surgery/stenting within 3 months before the screening visit
  4. History of bleeding disorders, esophageal varices, heparin induced thrombocytopenia, or contraindications to receiving heparin (eg, allergic reaction to heparin)
  5. Previous treatment with Glybera® in the past 5 years or treatment with lomitapide or mipomersen in the past 6 months
  6. Pregnant or breast feeding women
  Note: Other protocol defined Inclusion/Exclusion criteria may apply

Relevance to patient case: not relevant