Table 1.
Baseline demographics, disease characteristics, key cardiac biomarkers, and echocardiogram parameters of study population and exposure to study drug
| Placebo | Revusiran | Total | |
|---|---|---|---|
| (n = 66) | (n = 140) | (n = 206) | |
| Demographics | |||
| Age at randomization, years | |||
| Median (range) | 68.0 (38–81) | 69.0 (37–86) | 69.0 (37–86) |
| Age category, n (%) | |||
| 18–64 | 25 (37.9) | 41 (29.3) | 66 (32.0) |
| 65–74 | 29 (43.9) | 56 (40.0) | 85 (41.3) |
| ≥ 75 | 12 (18.2) | 43 (30.7) | 55 (26.7) |
| Sex, n (%) | |||
| Male | 53 (80.3) | 105 (75.0) | 158 (76.7) |
| Race, n (%) | |||
| White | 29 (43.9) | 66 (47.1) | 95 (46.1) |
| Black | 36 (54.5) | 68 (48.6) | 104 (50.5) |
| American Indian or Alaska Native | 1 (1.5) | 0 | 1 (0.5) |
| Other | 0 | 6 (4.3) | 6 (2.9) |
| Geographic region, n (%) | |||
| North America | 45 (68.2) | 96 (68.6) | 141 (68.4) |
| Western Europe | 21 (31.8) | 44 (31.4) | 65 (31.6) |
| Mean (SD) mBMI* | 1085.4 (196.8) | 1113.7 (253.5) | 1104.6 (236.6) |
| Disease characteristics | |||
| TTR mutation, n (%) | |||
| Val122Ile | 37 (56.1) | 80 (57.1) | 117 (56.8) |
| Thr60Ala | 12 (18.2) | 21 (15.0) | 33 (16.0) |
| Glu89Gln | 2 (3.0) | 3 (2.1) | 5 (2.4) |
| Other | 15 (22.7) | 36 (25.7) | 51 (24.8) |
| PND score, n (%) | |||
| 0 | 35 (53.0) | 62 (44.3) | 97 (47.1) |
| 1 | 20 (30.3) | 55 (39.3) | 75 (36.4) |
| 2 | 11 (16.7) | 23 (16.4) | 34 (16.5) |
| NYHA class, n (%) | |||
| I | 4 (6.1) | 13 (9.3) | 17 (8.3) |
| II | 42 (63.6) | 83 (59.3) | 125 (60.7) |
| III | 20 (30.3) | 44 (31.4) | 64 (31.1) |
| KCCQ Overall Summary Score (SD) | 65 (22.1) | 67 (20.0) | 67 (22.0) |
| Mean (SD) 6MWT at baseline, m | 400 (131.3) | 376 (117.6) | 383.6 (122.4) |
| Mean (SD) time from diagnosis to date of first dose, months† | 12 (12.4) | 15 (28.7) | 14 (24.7) |
| Renal impairment, n (%) | |||
| Normal: eGFR ≥ 90 ml/min/1.73 m2 | 7 (10.6) | 15 (10.7) | 22 (10.7) |
| Mild: eGFR ≥ 60 to < 90 ml/min/1.73 m2 | 28 (42.4) | 63 (45.0) | 91 (44.2) |
| Moderate: eGFR ≥ 30 to < 60 ml/min/1.73 m2 | 31 (47.0) | 62 (44.3) | 93 (45.1) |
| Medical history of peripheral neuropathy, n (%)‡ | 15 (22.7) | 36 (25.7) | 51 (24.8) |
| Key cardiac biomarkers and echocardiogram parameters | |||
| Median (range) troponin I, μg/l | 0.13 (0–0.95) | 0.12 (0–1.66) | 0.13 (0–1.66) |
| Median (range) NT-proBNP, pg/ml | 2719 (51–16,170) | 2371 (74–32,470) | 2511 (51–32,470) |
| Mean (SD) intraventricular septum thickness, mm | 18.6 (2.5) | 18.2 (2.6) | 18.3 (2.6) |
| Mean (SD) average peak longitudinal strain, % | −10.4 (3.6) | −11.0 (3.4) | −10.8 (3.5) |
| Mean (SD) left ventricular ejection fraction, % | 52.2 (10.3) | 53.1 (12.0) | 52.8 (11.5) |
| Mayo risk staging§ | |||
| High | 15 (23) | 36 (26) | 51 (25) |
| Intermediate | 19 (29) | 37 (26) | 56 (27) |
| Low | 32 (48) | 67 (48) | 99 (48) |
| Median (range) exposure to study drug‖ | 7.7 (2.1–16.4) | 6.7 (2.1–16.3) | – |
| Median (range) doses received | 37.5 (14–76) | 33.5 (13–76) | – |
Percentages are based on the number of patients randomized. Baseline was defined as the last value of the parameter prior to the first dose date
*mBMI was calculated as the product of BMI (kg/m2) and albumin (g/l).†Calculated as (date of first dose − date of diagnosis +1)/30.4.‡Based on standardized MedDRA HLT for peripheral neuropathy NEC.§Risk groups [24]: High risk – Both biomarkers above threshold at baseline; Intermediate risk – 1 above threshold at baseline; Low risk – Neither above at baseline. Biomarker thresholds – Troponin T > 0.05 ng/ml, NT-proBNP > 3000 pg/ml‖Duration of exposure in months was calculated as (the date of last dose of study drug – the date of the first dose of study drug +1)/30.4
6MWT 6-min walk test distance, eGFR estimated glomerular filtration rate, HLT high-level term, KCCQ Kansas City Cardiomyopathy Questionnaire, mBMI modified body mass index, NYHA New York Heart Association heart failure classification, MedDRA Medical Dictionary for Regulatory Affairs, NEC not elsewhere classified, NT-proBNP N-terminal prohormone of brain natriuretic peptide, PND polyneuropathy disability, SD standard deviation