TTR-mediated Amyloidosis
Conditions
Keywords
Cardiomyopathy, Heart Failure, FAC, Amyloid, Transthyretin, TTR, RNAi therapeutic
Brief summary
The purpose of this study was to evaluate the safety and clinical activity of long-term dosing with revusiran (ALN-TTRSC). Dosing has been discontinued; patients are being followed-up for safety.
Interventions
Sponsors
Alnylam Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Subjects who previously received and tolerated revusiran (ALN-TTRSC) in the ALN-TTRSC-002 study * Adequate liver function * Not Pregnant or nursing
Exclusion criteria
* Inadequate renal function * Uncontrolled hypertension, ischemic heart disease or clinically significant cardiac arrhythmia * Untreated hypo- or hyperthyroidism * Prior major organ transplant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability Results of Long-term Dosing With ALN-TTRSC (Revusiran) Transthyretin (TTR) Cardiac Amyloidosis Patients. | Day 0 up to 90 days post modified early termination visit (end of study); Mean duration of collection was 16 months | The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs) and study \[drug\] discontinuation. |
| Serum TTR Levels | Day 0 up to 90 days post modified early termination visit (end of study); Mean duration of collection was 16 months | Pharmacodynamic (PD) effect of long-term dosing of ALN-TTRSC on serum levels of TTR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality | Day 0 up to 90 days post modified early termination visit (end of study); Mean duration of collection was 16 months | Total number of deaths in the study and total number of deaths adjudicated as being related to cardiovascular causes. Deaths were adjudicated by an independent adjudication committee as cardiovascular (CV) or non-CV events. |
| Clinical Effects of Long-term Dosing of ALN-TTRSC on Hospitalization | Day 0 up to 90 days post modified early termination visit (end of study); Mean duration of collection was 16 months | Hospitalization events were adjudicated by an independent committee as cardiovascular (CV) or non-CV events |
| 6-minute Walk Test Performance | Baseline, Month 6, and Month 12 | Distance in meters walked in 6 minutes |
Countries
Canada, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Revusiran (ALN-TTRSC) All patients who received at least 1 dose of revusiran | 25 |
| Total | 25 |
Baseline characteristics
| Characteristic | Revusiran (ALN-TTRSC) |
|---|---|
| Age, Continuous | 68.8 years STANDARD_DEVIATION 6.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 21 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 25 |
| other Total, other adverse events | 25 / 25 |
| serious Total, serious adverse events | 22 / 25 |
Outcome results
Primary
Safety and Tolerability Results of Long-term Dosing With ALN-TTRSC (Revusiran) Transthyretin (TTR) Cardiac Amyloidosis Patients.
The proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs) and study \[drug\] discontinuation.
Time frame: Day 0 up to 90 days post modified early termination visit (end of study); Mean duration of collection was 16 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Revusiran (ALN-TTRSC) | Safety and Tolerability Results of Long-term Dosing With ALN-TTRSC (Revusiran) Transthyretin (TTR) Cardiac Amyloidosis Patients. | At least 1 SAE (serious adverse event) | 22 Participants |
| Revusiran (ALN-TTRSC) | Safety and Tolerability Results of Long-term Dosing With ALN-TTRSC (Revusiran) Transthyretin (TTR) Cardiac Amyloidosis Patients. | Study discontinuation for any reason | 18 Participants |
| Revusiran (ALN-TTRSC) | Safety and Tolerability Results of Long-term Dosing With ALN-TTRSC (Revusiran) Transthyretin (TTR) Cardiac Amyloidosis Patients. | At least 1 AE (adverse event) | 25 Participants |
Primary
Serum TTR Levels
Pharmacodynamic (PD) effect of long-term dosing of ALN-TTRSC on serum levels of TTR
Time frame: Day 0 up to 90 days post modified early termination visit (end of study); Mean duration of collection was 16 months
Population: Long term samples not collected due to study termination; no data to analyze
Secondary
6-minute Walk Test Performance
Distance in meters walked in 6 minutes
Time frame: Baseline, Month 6, and Month 12
Population: Number of participants analyzed differs from baseline to 6 and 12 months due to study discontinuations
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Revusiran (ALN-TTRSC) | 6-minute Walk Test Performance | Change from baseline at Month 6 | -20.6 meters | Standard Deviation 46.1 |
| Revusiran (ALN-TTRSC) | 6-minute Walk Test Performance | Change from baseline at Month 12 | -104.6 meters | Standard Deviation 88.6 |
Secondary
Clinical Effects of Long-term Dosing of ALN-TTRSC on Hospitalization
Hospitalization events were adjudicated by an independent committee as cardiovascular (CV) or non-CV events
Time frame: Day 0 up to 90 days post modified early termination visit (end of study); Mean duration of collection was 16 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Revusiran (ALN-TTRSC) | Clinical Effects of Long-term Dosing of ALN-TTRSC on Hospitalization | At least 1 hospitalization event on study | 17 Participants |
| Revusiran (ALN-TTRSC) | Clinical Effects of Long-term Dosing of ALN-TTRSC on Hospitalization | At least 1 CV hospitalization event | 15 Participants |
Secondary
Mortality
Total number of deaths in the study and total number of deaths adjudicated as being related to cardiovascular causes. Deaths were adjudicated by an independent adjudication committee as cardiovascular (CV) or non-CV events.
Time frame: Day 0 up to 90 days post modified early termination visit (end of study); Mean duration of collection was 16 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Revusiran (ALN-TTRSC) | Mortality | Total deaths | 8 Participants |
| Revusiran (ALN-TTRSC) | Mortality | Total CV mortality events | 6 Participants |