SNPMiner Trials (Home Page)
Report for Mutation V122I
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 3 clinical trials
Clinical Trials
1 The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy
Open-label, multicenter, international, single-treatment study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with V122I or wild-type TTR amyloid cardiomyopathy. The study will be conducted in two parts. Part 1 will include a six-week dosing period during which all enrolled patients will self-administer oral Fx-1006A 20 mg soft gelatin capsules once daily for six weeks. At Week 6, blood samples will be collected from each patient to determine TTR stabilization. Patients who complete the Week 6 visit will continue taking daily oral Fx 1006A 20 mg for up to a total of 12 months during Part 2 of this study. If it is determined that a patient is not stabilized at Week 6 (based on TTR stabilization data), the patient will be discontinued from the study. Safety and clinical outcomes will be evaluated during Part 2 of this study. Two whole blood samples for pharmacodynamic assessments (TTR stabilization) and pharmacokinetic assessments (Fx-1006A concentrations as well as calculated steady-state parameters) will be collected at Baseline and Week 6. At Months 6 and 12, two whole blood samples will be collected for pharmacodynamic assessments, and four whole blood samples (two samples per time point) will be collected for pharmacokinetic assessments to be utilized in population pharmacokinetic modeling. Echocardiography, chest x-ray, cardiac MRI, and 24-hour Holter monitoring will be conducted at Baseline, and Months 6 and 12. Six-minute walk test and quality of life utilizing the Patient Global Assessment, KCCQ, and SF-36 will be assessed at Baseline, and Months 3, 6, and 12. NYHA Classification will be assessed at Baseline, Week 6, and Months 3, 6, and 12. Serum markers of troponin I and T, and NT-pro-BNP levels will be assessed at each study visit. Safety and tolerability will be assessed throughout the study. Vital signs, 12-lead ECG, blood and urine samples for clinical laboratory tests (serum chemistry, hematology, coagulation panel, and urinalysis), AEs, and concomitant medications (including diuretic usage) will be assessed at each study visit. Abbreviated physical examinations will be conducted at Baseline, Weeks 2 and 6, and Months 3 and 6, and a complete physical examination will be conducted at Month 12. Clinic visits will be conducted during Screening (Days -30 to -1) and Baseline (Day 0); procedures scheduled for the Baseline visit may be conducted over a period of one week to accommodate patient scheduling. All Baseline procedures must be completed prior to the first self-administered dose on Day 1. Day 1 will be defined as administration of the first dose of study medication, which patients will self-administer at home. During treatment, clinic visits will be conducted at Week 2 (± 2 days), Week 6 (± 1 week), Month 3 (± 1 week), Month 6 (± 2 weeks), and Month 12 (± 2 weeks). Procedures scheduled for the Month 6 and 12 visits may occur over one week during the visit window to accommodate patient scheduling. Monthly telephone contacts (± 1 week of the scheduled date) will be made during months in which no clinical site visits are scheduled (Months 4, 5, 7, 8, 9, 10, and 11) for assessment of AEs and concomitant medications. A final telephone contact to assess AEs and concomitant medication usage will be made 30 days after the last dose of study medication for each patient. Patients who discontinue from the study at any time will have a final visit performed, including all safety assessments, at the time of discontinuation. Any patient discontinuing after the Month 6 visit will also have all exploratory assessments performed.
NCT00694161 Cardiomyopathy Drug: Fx-1006A MeSH:Cardiomyopathies
HPO:Cardiomyopathy
The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy. --- V122I ---
The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy Open-label, multicenter, international, single-treatment study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with V122I or wild-type TTR amyloid cardiomyopathy. --- V122I ---
The Effects Of Fx-1006A On Transthyretin Stabilization And Clinical Outcome Measures In Patients With V122I Or Wild-Type TTR Amyloid Cardiomyopathy Open-label, multicenter, international, single-treatment study designed to determine TTR stabilization as well as Fx-1006A safety and tolerability, and its effects on clinical outcomes in patients with V122I or wild-type TTR amyloid cardiomyopathy. --- V122I --- --- V122I ---
TTR amyloid cardiomyopathy is defined as: 1. Variant TTR amyloid cardiomyopathy as defined as: V122I genotype and presence of amyloid in cardiac biopsy tissue (as determined by congo red stain, alcin blue stain, or immunohistochemical TTR analysis), or 2. Variant TTR amyloid cardiomyopathy as defined as: V122I genotype, evidence of cardiac involvement by echocardiography with left ventricle wall thickness > 12 mm and presence of amyloid in non-cardiac biopsy tissue (as determined by congo red stain, alcin blue stain, or immunohistochemical TTR analysis), or 3. Wild-type TTR amyloid cardiomyopathy as defined as: normal TTR genotype and presence of TTR amyloid deposits in cardiac biopsy tissue (as determined by congo red stain and immunohistochemical TTR analysis), or 4. Wild-type TTR amyloid cardiomyopathy as defined as: normal TTR genotype, evidence of cardiac involvement by echocardiography with left ventricle wall thickness > 12 mm and presence of TTR amyloid deposits in non-cardiac biopsy tissue (as determined by congo red stain and immunohistochemical TTR analysis). --- V122I ---
TTR amyloid cardiomyopathy is defined as: 1. Variant TTR amyloid cardiomyopathy as defined as: V122I genotype and presence of amyloid in cardiac biopsy tissue (as determined by congo red stain, alcin blue stain, or immunohistochemical TTR analysis), or 2. Variant TTR amyloid cardiomyopathy as defined as: V122I genotype, evidence of cardiac involvement by echocardiography with left ventricle wall thickness > 12 mm and presence of amyloid in non-cardiac biopsy tissue (as determined by congo red stain, alcin blue stain, or immunohistochemical TTR analysis), or 3. Wild-type TTR amyloid cardiomyopathy as defined as: normal TTR genotype and presence of TTR amyloid deposits in cardiac biopsy tissue (as determined by congo red stain and immunohistochemical TTR analysis), or 4. Wild-type TTR amyloid cardiomyopathy as defined as: normal TTR genotype, evidence of cardiac involvement by echocardiography with left ventricle wall thickness > 12 mm and presence of TTR amyloid deposits in non-cardiac biopsy tissue (as determined by congo red stain and immunohistochemical TTR analysis). --- V122I --- --- V122I ---
2. Patient has a TTR mutation other than V122I. --- V122I ---
Primary Outcomes
Description: TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.
Measure: Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Week 6 Time: Week 6Secondary Outcomes
Description: TTR tetramer was assessed using a validated immunoturbidimetric assay. The Fraction of Initial (FOI) is the ratio of the measured TTR tetramer concentration after denaturation to the measured TTR tetramer concentration before denaturation. TTR tetramer stabilization is based on the difference between the on-treatment FOI and the baseline FOI expressed as a percentage of the baseline FOI.
Measure: Percentage of Participants With Stabilized Transthyretin (TTR Tetramer) at Month 6 and 12 Time: Month 6, Month 12Other Outcomes
Description: An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) Time: Baseline up to 30 days after the last doseDescription: An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state. On the basis of intensity, grade 3 was referred as severe, grade 4 as life-threatening and grade 5 as death.
Measure: Number of Participants With Greater Than or Equal to (>=) Grade 3 Treatment-Emergent AEs Time: Baseline up to 30 days after the last doseDescription: ECHO:investigator assessed test to assess cardiac function.ECHO abnormality criteria:any/valvular abnormality,pericardial effusion,abnormal regional wall motion,inferior vena cava respiratory variation,posterior left ventricular wall/septal thickness>=13 millimeter(mm),right ventricular thickness>=7mm,ejection fraction <50%, ratio of early (E) diastolic transmitral flow and atrial(A) contraction velocity (E/A)>=2, ratio of 'E'to lateral/septal mitral annular velocity (e') (E/e'prime lateral>15, E/e'prime septal>15), E deceleration time<=150 millisecond(msec),Isovolumic relaxation time<=70msec.
Measure: Number of Participants With Clinically Significant Treatment-Emergent Echocardiography (ECHO) Findings Time: Baseline up to Month 12Measure: Number of Participants Discontinuing From The Study Due to Clinically Significant Clinical or Laboratory Adverse Events (AEs) Time: Baseline up to Month 12
Description: Echocardiography was used to measure interventricular septal thickness (IVST), posterior left ventricular wall thickness (PLVWT), right ventricular wall thickness (RVWT), left atrial diameter (LAD): anterior-posterior (ant-post), medio-lateral, superior-inferior (sup-inf) and left ventricular end diastolic diameter (LVEDD).
Measure: Change From Baseline in Echocardiographic (ECHO) Parameters at Month 6 and 12 Time: Baseline, Month 6, Month 12Description: LVM was defined as increase in the mass of left ventricle, estimated by echocardiography. Increased LVM was associated with cardiovascular morbidity and mortality.
Measure: Change From Baseline in Left Ventricular Mass (LVM) at Month 6 and 12 Time: Baseline, Month 6, Month 12Description: Left ventricular ejection fraction (LVEF) was the fraction of the end-diastolic volume (EDV) that is ejected out of left ventricle with each contraction, estimated by echocardiography. EDV is the volume of blood within a ventricle immediately before a contraction.
Measure: Change From Baseline in Left Ventricular Ejection Fraction at Month 6 and 12 Time: Baseline, Month 6, Month 12Description: Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. Ratio of early (E) diastolic transmitral flow velocity and atrial (A) contraction velocity (E/A) and ratio of the early (E) diastolic transmitral flow velocity to the mitral annular velocity (e') (E/e') were estimated.
Measure: Change From Baseline in Doppler Data: E/A and E/e' Ratio at Month 6 and 12 Time: Baseline, Month 6, Month 12Description: Doppler echocardiography was a procedure which used ultrasound technology to examine the heart. The mitral deceleration time was the time taken from the maximum E wave to baseline. E wave arises due to early diastolic filling.
Measure: Change From Baseline in Doppler Data: Mitral Deceleration Time at Month 6 and 12 Time: Baseline, Month 6, Month 12Description: Tissue Doppler used doppler principles to measure the annular velocities at the lateral and septal areas of the mitral annulus. s': systolic velocity during ejection, e': early diastolic mitral annular velocity, a': late diastolic mitral annular velocity.
Measure: Change From Baseline in Tissue Doppler- Septal and Lateral Velocity at Month 6 and 12 Time: Baseline, Month 6, Month 12Description: Pericardial effusion was the presence of an abnormal amount of fluid in the pericardial cavity, as determined by echocardiography.
Measure: Change From Baseline in Pericardial Effusion at Month 6 and 12 Time: Baseline, Month 6, Month 12Description: Valvular abnormalities were those abnormalities (thickening or regurgitation) that involved one or more valves of the heart, determined by echocardiography.
Measure: Number of Participants With Change From Baseline in Valvular Abnormalities at Month 6 and 12 Time: Baseline, Month 6, Month 12Description: Cardiac Magnetic Resonance Imaging (MRI) was done to measure the thickness of left ventricular anteroseptal (LVAS) wall, left ventricular inferolateral (LVIL) wall and right ventricular end diastolic free (RVEDF) wall.
Measure: Change From Baseline in Left Ventricular Anteroseptal, Left Ventricular Inferolateral Wall Thickness and Right Ventricular End Diastolic Free Wall Thickness at Month 6 and 12 Time: Baseline, Month 6, Month 12Description: Cardiac MRI was done to measure LVM, mass of left ventricular (LV) myocardium with amyloidosis, mass of LV myocardium with fibrosis/scar and right ventricular end diastolic mass (RVEDM).
Measure: Change From Baseline in Left Ventricular Mass, Mass of Left Ventricular Myocardium With Amyloidosis, Mass of Left Ventricular Myocardium With Fibrosis/Scar and Right Ventricular End Diastolic Mass at Month 6 and 12 Time: Baseline, Month 6, Month 12Description: Cardiac MRI was done to measure left ventricle end diastolic volume (LVEDV), left ventricle end systolic volume (LVESV), left ventricle stroke volume (LVSV), right ventricle end diastolic volume (RVEDV), right ventricle end systolic volume (RVESV) and right ventricle stroke volume (RVSV).
Measure: Change From Baseline in Left Ventricle End Diastolic Volume, Left Ventricle End Systolic Volume, Left Ventricle Stroke Volume, Right Ventricle End Diastolic Volume, Right Ventricle End Systolic Volume, Right Ventricle Stroke Volume at Month 6 and 12. Time: Baseline, Month 6, Month 12Description: Cardiac MRI was done to measure: left ventricular ejection fraction (LVEF) was the fraction of the EDV that is ejected out of left ventricle with each contraction and right ventricular ejection fraction (RVEF) was the fraction of the EDV that is ejected out of right ventricle with each contraction. EDV is the volume of blood within a ventricle immediately before a contraction.
Measure: Change From Baseline in Left Ventricular Ejection Fraction and Right Ventricular Ejection Fraction at Month 6 and 12 Time: Baseline, Month 6, Month 12Description: Cardiac MRI was done to measure cardiac output, which was the volume of blood being pumped by the heart, in particular by the left or right ventricle in the time interval of one minute.
Measure: Change From Baseline in Left Ventricular Cardiac Output and Right Ventricular Cardiac Output at Month 6 and 12 Time: Baseline, Month 6, Month 12Description: Cardiac MRI was done to measure percentage of LV myocardial mass with amyloidosis and LV myocardial mass with fibrosis/scar. LV myocardial mass with amyloidosis or fibrosis/scar was calculated from the product of the myocardial volume and specific gravity of heart muscle, in participants with amyloidosis or fibrosis/scar, respectively.
Measure: Change From Baseline in Percentage of Left Ventricular Myocardial Mass With Amyloidosis and Left Ventricular Myocardial Mass With Fibrosis/Scar at Month 6 and 12 Time: Baseline, Month 6, Month 12Description: Cardiac MRI was done to measure interatrial septal thickness in the 4 chamber view.
Measure: Change From Baseline in 4 Chamber Interatrial Septal Thickness at Month 6 and 12 Time: Baseline, Month 6, Month 12Description: Cardiac MRI was done to measure the left and right atrial dimensions which have diagnostic and prognostic significance in cardiology, in the 4 chamber view.
Measure: Change From Baseline in 4 Chamber Left Atrial Dimension and 4 Chamber Right Atrial Dimension at Month 6 and 12 Time: Baseline, Month 6, Month 12Description: Holter monitor was a machine that recorded the heart rhythms. Holter monitoring abnormalities of atrial fibrillation/flutter (rapid, irregular heart rhythm), atrial tachycardia (rapid cardiac rate), non-sustained ventricular tachycardia (NSVT)<30 beats, sustained ventricular tachycardia (SVT) >=30 beats and sinus pause (transient interruption in the sinus rhythm) were recorded.
Measure: Number of Participants With Atrial Fibrillation/Flutter, Atrial Tachycardia, Non-Sustained Ventricular Tachycardia (NSVT) Beats), Sustained Ventricular Tachycardia (SVT), Sinus Pause at Month 6 and 12 Time: Baseline, Month 6, Month 12Description: Holter monitor was a machine that recorded the heart rhythms. 24-hour average heart rate and maximium/minimum heart rate was recorded using Holter monitoring.
Measure: 24-Hour Average Heart Rate and Maximium/Minimum Heart Rate Time: Baseline, Month 6, Month 12Description: Complete heart block is the third-degree atrioventricular block in which the impulse generated in the sinoatrial node in the atrium does not propagate to the ventricles.
Measure: Number of Participants With Complete Heart Block Time: Baseline, Month 6, Month 12Description: Holter monitor was a machine that recorded the heart rhythms. HRV time-domain indices were summarized for root-mean-square of successive differences [RMS SD] of the R-R intervals (R-R is the interval between successive Rs in the ECG wave) between normal beats (NN), magid standard deviation (Magid SD) of normal to normal R-R intervals and Kleiger standard deviation of normal to normal R-R intervals (Kleiger SD). The term 'NN' is used in place of 'R-R' when the processed beats are normal beats.
Measure: Heart Rate Variability (HRV)- Standard Deviation (SD) Parameters Time: Baseline, Month 6, Month 12Description: Holter monitor was a machine that recorded the heart rhythms. The term 'NN' was used in place of 'R-R' when the processed beats are normal beats. The percentage of successive R-R intervals with greater than 50 msec difference between normal beats was derived by dividing NN50 by the total number of NN intervals (pNN50), where NN50 was the number of interval differences of successive NN intervals greater than 50 msec.
Measure: Heart Rate Variability- Percentage of Successive R-R Intervals With Greater Than 50 Msec Difference Between Normal Beats (pNN50) Time: Baseline, Month 6, Month 12Description: NYHA: classified as 'class I' (participants with cardiac disease but without resulting limitations of physical activity), 'class II' (participants with cardiac disease resulting in slight limitation of physical activity), 'class III' (participants with cardiac disease resulting in marked limitation of physical activity), 'class IV' (participants with cardiac disease resulting in inability to carry on any physical activity without discomfort). Participants with change from baseline were classified as 'improved' (positive change), 'no change' or 'worsened' (negative change).
Measure: Number of Participants With Change From Baseline in New York Heart Association (NYHA) Classification at Week 6, Month 3, 6 and 12 Time: Baseline, Week 6, Month 3, Month 6, Month 12Description: Cardiothoracic ratio was defined as the transverse diameter of the heart, compared with that of the thoracic cage, used to help determine enlargement of the heart.
Measure: Cardiothoracic (CT) Ratio Time: Baseline, Month 6, Month 12Description: Chest x-ray was done to record the presence of increased interstitial markings (a large number of interstitial markings was indicative of abnormality in the lung) and pleural effusion, which was defined as accumulation of fluid between the layers of tissue that line the lungs and chest cavity.
Measure: Number of Participants With Increased Interstitial Markings and Pleural Effusions Time: Baseline, Month 6, Month 12Description: Participant's overall quality of life was measured by the PtGA. At baseline participants answered to question: "in general, how do you feel today?" - on a 5-point scale from '1' (excellent) to '5' (poor). At each follow-up visit, participant's answered to question: "How do you feel today as compared to when we talked with you at your last clinic visit for this study?" on a 7-point scale- '1' markedly improved, '2' moderately improved, '3' mildly improved, '4' unchanged, '5' mildly worsened, '6' moderately worsened, '7' markedly worsened.
Measure: Number of Participants With Change in Patient Global Assessment (PtGA) at Month 3, 6 and 12 Time: Baseline, Month 3, Month 6, Month 12Description: KCCQ was a 23-item heart failure specific questionnaire quantified in to following 10 summary scores: physical limitation, symptom frequency, symptom severity, and symptom stability, total symptoms, quality of life, social interference, self-efficacy, overall summary and clinical summary. Total score ranged from 0 to 100, where higher scores indicated better functioning, fewer symptoms, and better disease specific quality of life. Summary scores were scaled to range from 0 to 100, with higher scores representing greater disability.
Measure: Change From Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Score at Month 3, 6 and 12 Time: Baseline, Month 3, Month 6, Month 12Description: SF-36 was standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. Scores for the 8 domains range from 0-100, where higher scores were better (100=highest level of functioning) and reported as 2 summary scores; Mental Component Score (MCS) and Physical Component Score (PCS). The score for a section was an average of the individual question scores, which were scaled 0-100, where higher scores were better.
Measure: Change From Baseline in the Short Form 36 (SF-36) at Month 3, 6 and 12 Time: Baseline, Month 3, Month 6, Month 12Description: Troponin I and troponin T were the cardiac markers. Troponin I and troponin T were part of the troponin complex, where troponin I was bound to actin in thin myofilaments and troponin T was bound to tropomyosin. Higher level of these markers was indicative of heart damage.
Measure: Change From Baseline in Troponin I and Troponin T at Week 2, 6, Month 3, 6 and 12 Time: Baseline, Week 2, Week 6, Month 3, Month 6, Month 12Description: NT-proBNP was a cardiac marker which had the prognostic value for participants with heart failure or left ventricular dysfunction. Higher level of the marker was indicative of heart damage.
Measure: Change From Baseline in N-Terminal Prohormone Brain Natriuretic Peptide(NT-proBNP) Levels at Week 2, 6, Month 3, 6 and 12 Time: Baseline, Week 2, Week 6, Month 3, Month 6, Month 12Description: 6MWT was used to assess the distance that a participant could walk in 6 minutes. Participants were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. Continuous pulse oximetry was conducted during the test for safety.. The distance walked in 6 minutes was categorized as: Level 1: <300 meter, Level 2: 300-374.9 meter, Level 3: 375-449.9 meter, Level 4: >=450 meter.
Measure: Change From Baseline in 6-Minute Walk Test (6MWT) at Month 3, 6 and 12 Time: Baseline, Month 3, Month 6, Month 122 Screening for Cardiac Amyloidosis Using Nuclear Cardiology for Minority Populations
In this study, the investigators will recruit a cohort of elderly Black and Hispanic patients with heart failure to define the number of patients who have cardiac amyloidosis by utilizing highly sensitive heart imaging and blood tests. The investigators will also explore differences in genetics and sex as they relate to heart failure disease progression in cardiac amyloidosis.
NCT03812172 Amyloid Cardiomyopathy, Transthyretin-Related Drug: 99mTc-PYP MeSH:Cardiomyopathies Amyloidosis
HPO:Amyloidosis Cardiomyopathy
Among subjects with ATTR-CA we will determine the prevalence of ATTRwt and ATTRm from the Val122Ile mutation in Blacks and Caribbean Hispanics. --- Val122Ile ---
For hATTR, a substitution of isoleucine for valine (Val122Ile) is the most frequent TTR mutation in the US, observed exclusively in Black Americans with an allele frequency of 3.4%. --- Val122Ile ---
Primary Outcomes
Description: The prevalence of ATTR CA will be defined by the number of cases with significant myocardial retention of Tc-99 PYP including both ATTRwt and ATTRm CA as a percentage of total enrollment.
Measure: Prevalence of Transthyretin Cardiac Amyloidosis in Caribbean Hispanics and Blacks with heart failure (HF) Time: 5 yearsSecondary Outcomes
Description: Among subjects with ATTR-CA we will determine the prevalence of ATTRwt and ATTRm from the Val122Ile mutation in Blacks and Caribbean Hispanics
Measure: Prevalence of ATTRwt and ATTRm in Blacks and Caribbean Hispanics Time: 5 yearsDescription: The prevalence of ATTR cardiac amyloidosis will be calculated among men and women enrolled in this study
Measure: Sex distribution of ATTR cardiac amyloidosis Time: 5 yearsDescription: In the ATTR CA group alone, a composite time-to-first-event endpoint at 1-year of death, heart failure hospitalization, or 30% decline in 6-minute hall walk will be compared between ATTRwt and ATTRm subjects.
Measure: Disease progression in ATTRwt compared to ATTRm Time: 5 yearsDescription: Retinol binding protein 4 (RBB4) will be measured in urine.
Measure: RBP4 in Urine Time: 5 years3 A Phase 4 Multicenter Observational Study to Evaluate the Effectiveness of Patisiran in Patients With Polyneuropathy of Hereditary Transthyretin-Mediated (hATTR) Amyloidosis With a V122I or T60A Mutation
To evaluate the effectiveness of patisiran in patients with hATTR amyloidosis with polyneuropathy who have a V122I or T60A mutation.
NCT04201418 Hereditary Transthyretin-mediated (hATTR) Amyloidosis Polyneuropathy Drug: Patisiran MeSH:Polyneuropathies Amyloidosis
HPO:Amyloidosis Motor polyneuropathy Polyneuropathy
A Phase 4 Multicenter Observational Study to Evaluate the Effectiveness of Patisiran in Patients With Polyneuropathy of Hereditary Transthyretin-Mediated (hATTR) Amyloidosis With a V122I or T60A Mutation. --- V122I ---
A Multicenter Observational Study to Evaluate the Effectiveness of Patisiran in Patients With Polyneuropathy of hATTR Amyloidosis With a V122I or T60A Mutation To evaluate the effectiveness of patisiran in patients with hATTR amyloidosis with polyneuropathy who have a V122I or T60A mutation. --- V122I ---
A Multicenter Observational Study to Evaluate the Effectiveness of Patisiran in Patients With Polyneuropathy of hATTR Amyloidosis With a V122I or T60A Mutation To evaluate the effectiveness of patisiran in patients with hATTR amyloidosis with polyneuropathy who have a V122I or T60A mutation. --- V122I --- --- T60A --- --- V122I ---
PND Scores: Stage 0=No symptoms, Stage 1=Sensory disturbances but preserved walking capability, Stage 2=Impaired walking capacity, but ability to walk without a stick or crutches, Stage 3A/B=Walking with the help of 1 or 2 sticks or crutches, Stage 4=confined to wheel chair or bedridden.. Inclusion Criteria: - Diagnosed with hATTR amyloidosis with polyneuropathy, with a documented V122I or T60A mutation - PND score of I-IIIB at the baseline visit - Naive to patisiran treatment at the time of enrollment with intention to initiate treatment with patisiran. --- V122I ---
Exclusion Criteria: - New York Heart Association (NYHA) heart failure classification ≥3 - Karnofsky Performance Status (KPS) <60% - Unstable congestive heart failure (CHF) - Known primary amyloidosis (AL) or leptomeningeal amyloidosis - Prior major organ transplant - Previously received patisiran - Previous treatment with a TTR silencing therapy Inclusion Criteria: - Diagnosed with hATTR amyloidosis with polyneuropathy, with a documented V122I or T60A mutation - PND score of I-IIIB at the baseline visit - Naive to patisiran treatment at the time of enrollment with intention to initiate treatment with patisiran. --- V122I ---
Primary Outcomes
Description: PND Scores: Stage 0=No symptoms, Stage 1=Sensory disturbances but preserved walking capability, Stage 2=Impaired walking capacity, but ability to walk without a stick or crutches, Stage 3A/B=Walking with the help of 1 or 2 sticks or crutches, Stage 4=confined to wheel chair or bedridden.
Measure: Percentage of Participants with Stable or Improved Polyneuropathy Disability (PND) Score at 12 Months Relative to Baseline Time: Baseline, Month 12