Hereditary Transthyretin Amyloidosis With Polyneuropthy
Conditions
Keywords
Hereditary Transthyretin Amyloidosis, hATTR-PN, hATTR, Amyloidosis
Brief summary
The objective of the study was to characterize adverse events (AEs) occurring within one day of TEGSEDI administration to adult participants with hATTR-PN overall and in individual participants with respect to time course of AE onset, vital sign changes, preventive measures, treatment required, risk factors, and subsequent adverse outcomes.
Interventions
DRUGTEGSEDI
SC injection.
Sponsors
Akcea Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Satisfy one of the following: 1. United States (US) Participants: Adult participants (≥ 18 years old) diagnosed with hATTR-PN and prescribed TEGSEDI according to the United States Prescribing Information (USPI). 2. Canadian participants: Adult participants (≥ 18 years old) diagnosed with stage 1 or stage 2 hATTR-PN and prescribed TEGSEDI according to the Canadian Product Monograph (CPM). 2. Must have given written informed consent for participation in this study. 3. Must provide access to their previous medical records. 4. Are about to initiate or have recently initiated treatment with TEGSEDI and have not received more than 9 doses in total. 5. Be willing to complete required testing and report any AEs and/or changes in medications. 6. Satisfy one of the following: 1. Females: Non-pregnant and non-lactating; abstinent, or if engaged in sexual relations of childbearing potential, participant is using an acceptable contraceptive method from time of signing the informed consent form (ICF) until 13 weeks after the last dose of TEGSEDI administration 2. Males: Abstinent or if engaged in sexual relations with a female of childbearing potential, participant is utilizing an acceptable contraceptive method from the time of signing the ICF until 13 weeks after the last dose of TEGSEDI administration
Exclusion criteria
* None
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Incident, Onset and Duration of Treatment Emergent Adverse Events (TEAEs) Occurring Within 24 Hours of Each TEGSEDI Administration | Up to 2 years (24 hours post each TEGSEDI injection) | An adverse event (AE) is defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of medicinal product, whether or not the AE is considered related to the medicinal product. TEAEs are defined as AEs with an onset date/time on or after the date/time of the first on study administration of TEGSEDI. |
| Number of Participants With Clinically Significant Changes in Vital Signs | Up to 2 years (24 hours post each TEGSEDI injection) | Vital signs including body temperature, heart rate, respiratory rate, and systolic/diastolic blood pressure (BP). |
| Number of Participants With Clinically Significant Changes in Cytokine Levels and Inflammatory Markers | Up to 2 years (24 hours post each TEGSEDI injection) | Cytokines and inflammatory markers including the following parameters: Immunoglobulin (Ig)E, IgG, IgM, C-reactive protein, erythrocyte sedimentation rate, interferon-alpha, interferon beta, chemokines (macrophage inflammatory protein-1a and membrane cofactor protein-1, granulocyte-macrophage colony-stimulating factor, Interleukin (IL)-1alpha (α), IL-1 beta (β), IL-6, IL-8, IL-12, and tumor necrosis factor-α. |
Countries
Canada, United States
Participant flow
Recruitment details
Participants took part at 2 clinical sites in the United States of America (USA) and Canada from 21 January 2021 to 20 March 2024.
Pre-assignment details
A total of 8 participants with polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) were screened for the study, of which 7 participants were treated with TEGSEDI. The 8th participant was enrolled after the sponsor had notified the sites about the study close-out activities, therefore only 7 participants were included in the study.
Participants by arm
| Arm | Count |
|---|---|
| TEGSEDI Participants with hATTR-PN received TEGSEDI 284 mg, SC once weekly, as prescribed by their physician per the product label. | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Enrolled but Not Treated | 1 |
| Overall Study | Voluntarily withdrawal | 1 |
Baseline characteristics
| Characteristic | TEGSEDI |
|---|---|
| Age, Continuous | 67.6 years STANDARD_DEVIATION 8.62 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 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 | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 7 |
| other Total, other adverse events | 6 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
Number of Participants With Clinically Significant Changes in Cytokine Levels and Inflammatory Markers
Cytokines and inflammatory markers including the following parameters: Immunoglobulin (Ig)E, IgG, IgM, C-reactive protein, erythrocyte sedimentation rate, interferon-alpha, interferon beta, chemokines (macrophage inflammatory protein-1a and membrane cofactor protein-1, granulocyte-macrophage colony-stimulating factor, Interleukin (IL)-1alpha (α), IL-1 beta (β), IL-6, IL-8, IL-12, and tumor necrosis factor-α.
Time frame: Up to 2 years (24 hours post each TEGSEDI injection)
Population: The evaluable set included participants in the safety set having at least 1 post-dose assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TEGSEDI | Number of Participants With Clinically Significant Changes in Cytokine Levels and Inflammatory Markers | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Vital Signs
Vital signs including body temperature, heart rate, respiratory rate, and systolic/diastolic blood pressure (BP).
Time frame: Up to 2 years (24 hours post each TEGSEDI injection)
Population: The evaluable set included participants in the safety set having at least 1 post-dose assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TEGSEDI | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
Primary
Number of Participants With Incident, Onset and Duration of Treatment Emergent Adverse Events (TEAEs) Occurring Within 24 Hours of Each TEGSEDI Administration
An adverse event (AE) is defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of medicinal product, whether or not the AE is considered related to the medicinal product. TEAEs are defined as AEs with an onset date/time on or after the date/time of the first on study administration of TEGSEDI.
Time frame: Up to 2 years (24 hours post each TEGSEDI injection)
Population: The evaluable set included participants in the safety set having at least 1 post-dose assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| TEGSEDI | Number of Participants With Incident, Onset and Duration of Treatment Emergent Adverse Events (TEAEs) Occurring Within 24 Hours of Each TEGSEDI Administration | 3 Participants |