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

Clinical trial: Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia (ODYSSEY HIGH FH)

Summary: Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9).
  Primary Objective of the study:
  To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 24 weeks of treatment in comparison with placebo.
  Secondary Objectives:
  -  To evaluate the effect of alirocumab in comparison with placebo on LDL-C at other time points
  -  To evaluate the effects of alirocumab on other lipid parameters
  -  To evaluate the safety and tolerability of alirocumab

Detailed description: The maximum study duration was planned to be 89 weeks per participant including participants who successfully completed the 78-week treatment period had the possibility to join an open-label extension study (LTS13463, NCT01954394) at the end of the treatment period.

Eligibility: Inclusion criteria:
  -  Participants with heterozygous familial hypercholesterolemia who were not adequately controlled with their lipid-modifying therapy.
  Exclusion criteria:
  -  Age < 18 years
  -  LDL-C < 160 mg/dL (< 4.14 mmol/L) at the screening visit (Week-3).
  -  Fasting serum triglycerides > 400 mg/dL (> 4.52 mmol/L) during the screening period.
  -  Known history of homozygous familial hypercholesterolemia.
  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: Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Placebo on Top of Lipid-Modifying Therapy in Patients With Heterozygous Familial Hypercholesterolemia Not Adequately Controlled With Their Lipid-Modifying Therapy

Summary: Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9).
  Primary Objective of the study:
  To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 24 weeks of treatment in comparison with placebo.
  Secondary Objectives:
  -  To evaluate the effect of alirocumab in comparison with placebo on LDL-C at other time points
  -  To evaluate the effects of alirocumab on other lipid parameters
  -  To evaluate the safety and tolerability of alirocumab

Detailed description: The maximum study duration was planned to be 89 weeks per participant including participants who successfully completed the 78-week treatment period had the possibility to join an open-label extension study (LTS13463, NCT01954394) at the end of the treatment period.

Eligibility: Inclusion criteria:
  -  Participants with heterozygous familial hypercholesterolemia who were not adequately controlled with their lipid-modifying therapy
  Exclusion criteria:
  -  Age < 18 years or legal age of adulthood, whichever is greater
  -  LDL-C < 70 mg/dL (1.81 mmol/L) and with cardiovascular disease
  -  LDL-C < 100 mg/dL (2.59 mmol/L) and without cardiovascular disease
  -  Fasting serum triglycerides > 400 mg/dL (4.52 mmol/L)
  -  Known history of homozygous familial hypercholesterolemia
  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: Trial Assessing Long Term USe of PCSK9 Inhibition in Subjects With Genetic LDL Disorders

Summary: A study to assess the long term safety and tolerability of evolocumab (AMG 145) in adolescents and adults with severe familial hypercholesterolemia.

Detailed description: This phase 2/3 open-label extension study was designed to characterize the safety and tolerability of long-term administration of evolocumab to adults and adolescents with severe FH (HoFH or non-HoFH severe FH). Participants not on lipid apheresis at enrollment or within the prior 8 weeks initiated treatment with evolocumab 420 mg once monthly (QM). Participants on lipid apheresis at enrollment initiated treatment with evolocumab 420 mg once every 2 weeks (Q2W). Dose frequency changes (420 mg QM vs 420 mg Q2W) were permitted at week 12, 24, or other visits with Sponsor approval. Participants with < 5% LDL-C reduction from baseline and serum unbound proprotein convertase subtilisin/kexin type 9 (PCSK9) < 100 ng/mL could discontinue evolocumab. If serum unbound PCSK9 was ≥ 100 ng/mL with QM dosing, the participant could switch to evolocumab 420 mg Q2W treatment. Participants on apheresis with ≥ 5% LDL-C reduction from baseline and serum unbound PCSK9 < 100 ng/mL with Q2W treatment could switch to QM dosing.
  Participants were to continue to receive open-label evolocumab for up to 5 years or until evolocumab became commercially available in the relevant patient population, whichever occurred first.

Eligibility: Inclusion Criteria:
  - Participated in Study 20110233 (NCT01588496) or another qualifying evolocumab parent protocol and have a diagnosis of familial hypercholesterolemia.
  OR
  -  Have a diagnosis of familial hypercholesterolemia AND
  -  Males and females ≥ 12 to ≤ 80 years of age
  -  Stable low-fat diet and lipid-lowering therapies for at least 4 weeks
  -  Low-density lipoprotein cholesterol (LDL-C) >= 130 mg/dl (3.4 mmol/L) for subjects without diagnosed coronary heart disease (CHD)/CHD risk equivalent OR LDL-C >= 100 mg/dl (2.6 mmol/L) for subjects with diagnosed CHD or CHD risk equivalent OR apheresis patients have no LDL-C entry requirement
  -  Fasting triglycerides ≤ 400 mg/dL(4.5 mmol/L)
  -  Body weight of > 40 kg or greater at screening for subjects less than 18 years of age
  Exclusion Criteria:
  -  New York Heart Failure Association (NYHA) class III or IV or last known left ventricular ejection fraction < 30%
  -  Myocardial infarction, unstable angina, percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG) or stroke within 3 months of screening
  -  Planned cardiac surgery or revascularization
  -  Uncontrolled cardiac arrhythmia
  -  Uncontrolled hypertension

Relevance to patient case: definitely relevant
Patient case: 24-year-old female with familial hypercholesterolemia; genetic feature: PCSK9

Clinical trial: Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe on Top of Statin in High Cardiovascular Risk Patients With Hypercholesterolemia (ODYSSEY COMBO II)

Summary: Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9).
  Primary Objective of the study:
  To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab as add-on therapy to stable maximally tolerated daily statin therapy in comparison with ezetimibe after 24 weeks of treatment in participants with hypercholesterolemia at high cardiovascular (CV) risk.
  Secondary Objectives:
  -  To evaluate the effect of alirocumab in comparison with ezetimibe on LDL-C at other time points
  -  To evaluate the effect of alirocumab on other lipid parameters
  -  To evaluate the safety and tolerability of alirocumab

Detailed description: The maximum study duration was 115 weeks per participant, including a 3-week screening period, 104-week randomized treatment period and 8-week follow-up period.

Eligibility: Inclusion criteria:
  Participants with hypercholesterolemia and established coronary heart disease (CHD) or CHD risk equivalents who were not adequately controlled with a maximally tolerated daily dose of statin at stable dose for at least 4 weeks prior to the screening visit (Week -2).
  Exclusion criteria:
  -  Age < 18 or legal age of adulthood, whichever was greater
  -  Participants without established CHD or CHD risk equivalents
  -  LDL-C <70 mg/dL (<1.81 mmol/L) and participants with a history of documented cardiovascular disease
  -  LDL-C <100 mg/dL (<2.59 mmol/L) and participants without a history of documented CV disease
  -  Fasting serum triglycerides >400 mg/dL (>4.52 mmol/L)
  The above information was 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: Efficacy and Safety of Alirocumab (SAR236553/REGN727) Versus Ezetimibe in Patients With Hypercholesterolemia

Summary: Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds PCSK9 (proprotein convertase subtilisin/kexin type 9).
  Primary Objective of the study:
  To demonstrate the reduction of low-density lipoprotein cholesterol (LDL-C) by alirocumab in comparison with ezetimibe after 24 weeks of treatment in participants with hypercholesterolemia.
  Secondary Objectives:
  -  To evaluate the effect of alirocumab in comparison with ezetimibe on LDL-C at other time points
  -  To evaluate the effect of alirocumab on other lipid parameters
  -  To evaluate the safety and tolerability of alirocumab

Detailed description: The maximum study duration was 34 weeks per participant, including a 24-week randomized treatment period.

Eligibility: Inclusion criteria:
  -  Participants with hypercholesterolemia
  Exclusion criteria:
  -  Age < 18 or legal age of adulthood, whichever was greater
  -  LDL-C < 100 mg/dL (< 2.59 mmol/L) or > 190 mg/dL (> 4.9 mmol/L)
  -  Fasting serum triglycerides (TG) > 400 mg/dL (> 4.52 mmol/L)
  -  Known history of homozygous or heterozygous familial hypercholesterolemia
  The above information was 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: Pharmacokinetic and Tolerability of Alirocumab SAR236553 (REGN727) in Patients With Hepatic Impairment and in Healthy Subjects

Summary: Primary Objective:
  Study the effect of mild or moderate hepatic impairment on the pharmacokinetics of alirocumab SAR236553 (REGN727).
  Secondary Objectives:
  -  Assess the safety and tolerability of alirocumab SAR236553 (REGN727) in patients with mild and moderate hepatic impairment and in matched subjects with normal hepatic function.
  -  Assess the pharmacodynamic profile of alirocumab SAR236553 (REGN727) in patients with hepatic impairment and in matched subjects with normal hepatic function.

Detailed description: Total duration of the study per subject (excluding screening) is about 12 weeks.

Eligibility: Inclusion criteria :
  -  Male or female, between 18 to 75 years of age, inclusive.
  -  Patients with mild and moderate hepatic impairment based on Child-Pugh score and stable chronic liver disease.
  -  Healthy subjects with normal hepatic function.
  Exclusion criteria:
  -  Patients with acute hepatitis, hepatic encephalopathy grade 2, 3, and 4.
  -  Patients with history or presence of uncontrolled clinically relevant illness.
  -  Healthy subjects with history or presence of clinically relevant illness.
  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: Effect of Alirocumab (SAR236553/REGN727) Administered on Top of Ezetimibe or Fenofibrate on Lipid Profiles in Healthy Subjects

Summary: Primary Objective:
  To assess the pharmacodynamic profile of alirocumab (SAR236553/REGN727) administered either alone or on top of ezetimibe or fenofibrate, based on low-density lipoprotein -cholesterol (LDL-C).
  Secondary Objectives:
  -  To assess the pharmacodynamic profile of alirocumab administered either alone or on top of ezetimibe or fenofibrate, based on other lipid parameters.
  -  To assess the pharmacokinetic profile of alirocumab administered either alone or on top of ezetimibe or fenofibrate.

Detailed description: Total duration of the study per subject (excluding screening) is about 22 weeks.

Eligibility: Inclusion criteria :
  -  Healthy male /or female subjects,
  -  aged 18 to 65 years old,
  -  with LDL-C > 130 mg/dL
  -  not receiving lipid lowering therapy.
  Exclusion criteria:
  -  Healthy subjects with history or presence of clinically relevant illness.
  -  Subjects currently taking statins, ezetimibe or fenofibrate.
  -  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: Study of the Efficacy and Safety of Alirocumab (REGN727/SAR236553) in Combination With Other Lipid-modifying Treatment (LMT) (ODYSSEY OPTIONS I)

Summary: This is a randomized, double-blind, active-comparator, parallel-group study in patients at high cardiovascular risk with nonfamilial hypercholesterolemia or heterozygous familial hypercholesterolemia (heFH).


Eligibility: Inclusion Criteria:
  1. Patients with screening (visit 1) LDL-C greater than or equal to 70 mg/dL with documented CVD, not adequately controlled with a daily dose of atorvastatin. OR
  2. Patients with screening (visit 1) LDL-C greater than or equal to 100 mg/dL at high risk for CVD who are not adequately controlled with a daily dose of atorvastatin.
  Exclusion Criteria:
  1. LDL-C greater than 250 mg/dL
  2. LDL-C less than 70 mg/dL at the screening visit in patients with history of documented CVD
  3. LDL-C less than 100 mg/dL at the screening visit in patients without history of documented CHD or non-CHD CVD, but with other risk factors
  4. TG greater than 400 mg/dL
  5. Homozygous FH (clinically or previous genotyping)
  6. Currently taking a statin that is not atorvastatin
  7. Currently taking Ezetimibe (EZE)
  8. Not on a stable dose of allowable lipid modifying treatments (LMT)
  (The inclusion/ exclusion criteria provided above is not intended to contain all considerations relevant to a patient's potential participation in this clinical trial).

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

Clinical trial: Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects -2

Summary: The primary objective was to evaluate the effect of 12 weeks of subcutaneous (SC) evolocumab every 2 weeks (Q2W) and monthly (QM), compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic adults unable to tolerate an effective dose of a statin (HMG-CoA (5-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors).


Eligibility: Inclusion Criteria:
  -  Male or female ≥ 18 to ≤ 80 years of age
  -  Not on a statin or on a low dose statin with stable dose for at least 4 weeks
  -  History of intolerance to at least 2 statins
  -  Subject not at LDL-C goal
  -  Lipid lowering therapy has been stable prior to enrolment for at least 4 weeks.
  -  Fasting triglycerides ≤ 400 mg/dL
  Exclusion Criteria:
  -  New York Heart Association (NYHA) III or IV heart failure
  -  Uncontrolled cardiac arrhythmia
  -  Uncontrolled hypertension
  -  Type 1 diabetes, poorly controlled type 2 diabetes
  -  Uncontrolled hypothyroidism or hyperthyroidism

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

Clinical trial: Reduction of LDL-C With PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder Study-2

Summary: The primary objective was to evaluate the effect of 12 weeks of evolocumab subcutaneously once every 2 weeks (Q2W) and once monthly (QM), compared with placebo, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in adults with heterozygous familial hypercholesterolemia (HeFH).


Eligibility: Inclusion Criteria:
  -  Male or female ≥ 18 to ≤ 80 years of age
  -  Diagnosis of heterozygous familial hypercholesterolemia
  -  On a stable dose of an approved statin and lipid regulating medication
  -  Fasting LDL-C ≥ 100 mg/dL (2.6 mmol/L)
  -  Fasting triglycerides ≤ 400 mg/dL (4.5 mmol/L)
  Exclusion Criteria:
  -  Homozygous familial hypercholesterolemia
  -  LDL or plasma apheresis
  -  New York Heart Association (NYHA) III or IV heart failure
  -  Uncontrolled cardiac arrhythmia
  -  Uncontrolled hypertension
  -  Type 1 diabetes, poorly controlled type 2 diabetes
  -  Uncontrolled hypothyroidism or hyperthyroidism

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

Clinical trial: Consumption of Whole Grains and Legumes Modulates the Genetic Effect of the APOA5 -1131C Variant

Summary: We examined whether a substitution of whole grains and legumes for refined rice in a high carbohydrate diet (about 65% of energy derived from carbohydrate) may modify the effect of this variant on changes in apolipoprotein A-V (apoA-V) and triglyceride concentrations.

Detailed description: We genotyped the APOA5 -1131T>C in individuals with impaired fasting glucose (IFG) or newly diagnosed type 2 diabetes, who were randomly assigned to either a group ingesting whole grain and legume meals daily or a control group for 12 weeks.

Eligibility: Inclusion Criteria:
  -  Subjects who were in in impaired fasting glucose (IFG, 100≤ fasting glucose <126 mg/dL) and newly diagnosed type 2 diabetes (fasting glucose ≥126 mg/dL) were referred to the Department of Family Medicine or Internal Medicine. They were rechecked for their health and lipid profiles, and then those who satisfied the study criteria were recommended to participate in the dietary intervention program
  Exclusion Criteria:
  -  Current and/or past history of cardiovascular disease including angina
  -  Liver or kidney dysfunction
  -  Thyroid or pituitary disease
  -  Unstable weight loss/gain (≥2 kg) over the previous 6months
  -  Pregnancy or lactation. Subjects who were taking medication were also excluded

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

Clinical trial: Impact of a Short-Term High Fat or Low Fat Diet on Intestinal Genes Expression Involved in the Cholesterol and Fatty Acid Metabolism

Summary: Dietary fat has been shown to modulate cholesterol and fatty acids homeostasis and several lines of evidence suggest that this effect is associated with changes in the regulation of different genes at the intestine level involved in the cholesterol and fatty acid metabolism pathways. The present study will examine the impact of a short-term high fat diet versus a short-term low fat diet on expression of Niemann-Pick C1-like 1 (NPC1L1), adenosine triphosphate (ATP) binding cassette transporters (ABCG5/8), microsomal triglyceride transfer protein (MTP) and fatty acid transport protein-4 (FATP4), which have been shown to play a critical role in intestinal cholesterol absorption, chylomicron synthesis and dietary lipid absorption. Gene expression studies will be performed on duodenal biopsies. The primary hypothesis is that a short-term high fat diet will significantly decrease duodenal messenger ribonucleic acid (mRNA) levels of NPC1L1, ABCG5/8, MTP and FATP4 as compared with a short-term low fat diet.


Eligibility: Inclusion Criteria:
  -  Males 18 to 50 years of age
  -  Non-smoker
  -  Body mass index between 20.0 and 30.0 kg/m2
  -  Plasma LDL-cholesterol levels between the 25th and 75th percentile for their age at day -14
  -  Plasma triglyceride levels < 1.7 mmol/L (150 mg/dl) at day -14
  -  Plasma HDL-cholesterol levels between 0.9 (35 mg/dl) and 1.6 mmol/L (60 mg/dl) at day -14
  -  Subjects must be willing to give written informed consent and able to adhere to the diet schedule and visit schedule
  -  Patients should be otherwise healthy, without elevations in hepatic transaminases or creatine kinase (CK) or abnormal renal function or coagulation
  Exclusion Criteria:
  -  Patients with extreme dyslipidemias, such as familial hypercholesterolemia will be excluded
  -  Subjects will be excluded if they have cardiovascular disease (CHD, cerebrovascular disease or peripheral arterial disease) or if they are taking other medications known to affect lipoprotein metabolism (eg. steroids, beta blockers, thiazide diuretics, other lipid lowering agents, significant alcohol intake etc.)

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

Clinical trial: Efficacy and Safety Evaluation of Alirocumab (SAR236553/REGN727) in Patients With Primary Hypercholesterolemia on Stable Atorvastatin Therapy in Japan

Summary: Alirocumab (SAR236553/REGN727) is a fully human monoclonal antibody that binds proprotein convertase subtilisin/kexin type 9 (PCSK9).
  Primary Objective of the study:
  To evaluate the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C) levels after 12 weeks of treatment in comparison with placebo in participants with LDL-C ≥100 mg/dL (≥2.59 mmol/L) on ongoing stable atorvastatin therapy.
  Secondary Objectives:
  -  To evaluate the effects of alirocumab on other lipid levels after 12 weeks of treatment in comparison with placebo
  -  To evaluate the safety and tolerability of alirocumab
  -  To evaluate the development of anti-alirocumab antibodies
  -  To evaluate the pharmacokinetics of alirocumab

Detailed description: The duration of study participation depended on the status of the participant at screening: 21 to 27 weeks including a screening/run-in period of 1 to 7 weeks, a double-blind treatment period of 12 weeks, followed by an 8-week follow-up period.

Eligibility: Inclusion criteria :
  - Participants with primary hypercholesterolemia treated with atorvastatin at stable dose of 5-20 mg for at least 6 weeks prior to screening and likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) at the screening visit.
  OR
  - Participants with primary hypercholesterolemia who were receiving a lipid-lowering treatment other than atorvastatin, or who were not at stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening if they were likely to have LDL-C ≥100 mg/dL (≥2.59 mmol/L) after a 6-week run-in treatment period on atorvastatin therapy.
  Exclusion criteria:
  1. LDL-C <100 mg/dL (<2.59 mmol/L)
  -  at screening visit for participants who were being treated with stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening OR
  -  at the end of the 6-week run-in period on atorvastatin for participants receiving a lipid lowering treatment other than atorvastatin, or not at stable dose of atorvastatin 5-20 mg for at least 6 weeks prior to screening
  2. Participants with type 1 diabetes
  3. Participants with type 2 diabetes treated with insulin, or without, and considered poorly controlled at screening.
  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