CClinicalTrials.gg
TerminatedNCT04306510Updated Apr 10, 2025Results posted

A Study to Characterize Adverse Events Occurring Within One Day of TEGSEDI Administration to Adult Participants With hATTR-PN

A Phase 4 interventional study of TEGSEDI in Hereditary Transthyretin Amyloidosis With Polyneuropthy, sponsored by Akcea Therapeutics. Terminated at 2 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-04-10.

Sponsored by Akcea Therapeutics · Phase 4, Interventional, and Other

Why this study was terminated
Withdrawal of TEGSEDI from sale was not related to any safety issues.
Phase
Phase 4
Study type
Interventional
Enrollment
8
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Hereditary Transthyretin Amyloidosis With Polyneuropthy

Keywords

  • Hereditary Transthyretin Amyloidosis
  • hATTR-PN
  • hATTR
  • Amyloidosis
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts 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

Exclusion Criteria:

  • None
04

Study design

Phase
Phase 4
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
8 participants (actual)

Study arms

  • Experimental
    TEGSEDI

    Participants received TEGSEDI 284 milligrams (mg), subcutaneously (SC) once weekly, as prescribed by their physician per the product label.

    Drug: TEGSEDI

Interventions

  • DrugTEGSEDI

    SC injection.

    Also known as: Inotersen

05

What researchers measure

Primary outcomes

  1. 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)

  2. 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)

  3. 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)

06

Results

Posted Apr 10, 2025
Limitations and caveats
This study was subject to limitations due to the rarity of hATTR-PN, which limits the enrollment of potentially eligible patients. Additionally, the availability of concurrent clinical trials and newer therapies targeting the same patient population further complicated efforts to achieve the planned enrollment.

Participant flow

Participants took part at 2 clinical sites in the United States of America (USA) and Canada from 21 January 2021 to 20 March 2024.

Participant flow — Overall Study
MilestoneTEGSEDI
Started8
Completed6
Not completed2
Withdrew: Voluntarily withdrawal1
Withdrew: Enrolled but not treated1

Outcome measures

PrimaryNumber 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)
Reported as:
Count of participants · Participants
Number of Participants With Incident, Onset and Duration of Treatment Emergent Adverse Events (TEAEs) Occurring Within 24 Hours of Each TEGSEDI Administration
ParticipantsTEGSEDI
Number of Participants With Incident, Onset and Duration of Treatment Emergent Adverse Events (TEAEs) Occurring Within 24 Hours of Each TEGSEDI Administration3
PrimaryNumber 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)
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Changes in Vital Signs
ParticipantsTEGSEDI
Number of Participants With Clinically Significant Changes in Vital Signs0
PrimaryNumber 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)
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Changes in Cytokine Levels and Inflammatory Markers
ParticipantsTEGSEDI
Number of Participants With Clinically Significant Changes in Cytokine Levels and Inflammatory Markers0

Adverse events

Collected over Up to 2 years (24 hours post each TEGSEDI injection). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
TEGSEDI0/7 (0%)0/7 (0%)6/7 (85.7%)
Most frequent other events
Showing 10 of 11
Most frequent other events
EventTEGSEDI
Injection site painGeneral disorders2/7
ChillsGeneral disorders1/7
Influenza like illnessGeneral disorders1/7
Injection site discomfortGeneral disorders1/7
MyalgiaMusculoskeletal and connective tissue disorders1/7
Pain in extremityMusculoskeletal and connective tissue disorders1/7
DiarrhoeaGastrointestinal disorders1/7
NauseaGastrointestinal disorders1/7
Decreased appetiteMetabolism and nutrition disorders1/7
DizzinessNervous system disorders1/7

Baseline characteristics

The safety set included all participants who received at least 1 dose of TEGSEDI while enrolled in this study protocol.

Age, Continuous
Age, Continuous(years)TEGSEDI
Mean67.6 ± 8.62
Sex: Female, Male
Sex: Female, Male(Participants)TEGSEDI
Female4
Male3
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)TEGSEDI
Hispanic or Latino1
Not Hispanic or Latino6
Unknown or Not Reported0
Race (NIH/OMB)
Race (NIH/OMB)(Participants)TEGSEDI
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander2
Black or African American4
White1
More than one race0
Unknown or Not Reported0
07

Study locations

2 sites
  • Study Center
    Rosedale, New York 11422, United States
  • Study Center
    Toronto, Ontario M3K0A6, Canada
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Oct 6, 2023

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT04306510
Lead sponsor
Akcea Therapeutics
Responsible party
Sponsor
First posted
Mar 13, 2020
Start date
Jan 21, 2021
Primary completion
Mar 20, 2024
Completion
Mar 20, 2024
Results posted
Apr 10, 2025
Last update
Apr 10, 2025

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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