Efficacy and Safety of Acoramidis (AG10) in Subjects With Transthyretin Amyloid Polyneurophathy (ATTRibute-PN)

January 26, 2022 updated by: Eidos Therapeutics, a BridgeBio company

A Phase 3, Open-Label, Multicenter, Single-Arm Study to Evaluate the Efficacy and Safety of Acoramidis in Subjects With Symptomatic Transthyretin Amyloid Polyneuropathy (ATTRibute-PN Study)

Phase 3 efficacy and safety of acoramidis in subjects with symptomatic Transthyretin Amyloid Polyneuropathy (ATTR-PN)

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Transthyretin amyloid polyneuropathy (ATTR-PN), also called "Familial Transthyretin-Mediated Amyloid Polyneuropathy (FAP)" is a hereditary condition caused by mutations in the TTR gene. It is estimated that around 10,000 people in the world are affected.

In ATTR-PN, amyloid builds up in the nerves that detect temperature, pain, and touch. Patients with ATTR-PN can experience a loss of sensation, tingling, numbness, or pain in the hands and feet (also called peripheral neuropathy).

In this study Eidos, a BridgeBio Company, is researching the investigational drug acoramidis (AG10) hydrochloride (HCl) 800mg administered orally twice a day. Through the study, Eidos/BridgeBio wants to evaluate the efficacy and safety of acoramidis in patients with ATTR-PN.

The primary outcome of the study is to determine the efficacy of acoramidis in the treatment of subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN).

At the end of 18 months, participants will be eligible to continue to receive acoramidis to evaluate the long-term safety and tolerability of acoramidis.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female ≥18 to ≤90 years of age;
  • Have Stage I or II symptoms (polyneuropathy disability [PND] ≤IIIb) of ATTR-PN and an established diagnosis of ATTR-PN as defined by physical examination findings and/or neurophysiological test findings consistent with the diagnosis of ATTR-PN;
  • Have an NIS of 5 to 130 (inclusive) during Screening;
  • Have a nerve conduction studies (NCS) score (sum of the sural sensory nerve action potential [SNAP], tibial compound muscle action potential (CMAP), ulnar SNAP, ulnar CMAP, and peroneal CMAP) of ≥2 points during Screening. NCS is a component of mNIS+7;
  • Have a mutation consistent with ATTR-PN either documented in medical history or confirmed by genotyping obtained at Screening prior to enrollment. No genetic testing is needed for subjects who are recipients of domino liver transplants;
  • Have an anticipated survival of >2 years in the opinion of the investigator;
  • Have Karnofsky performance status ≥60 %.

Exclusion Criteria:

  • Had a prior liver transplantation or is planning to undergo liver transplantation with a wild-type organ graft as treatment for symptomatic ATTR-PN during the study period. Note: Recipients of a "domino" liver transplant from an ATTR-PN donor who have developed ATTR-PN mediated by their graft are allowed under this protocol, as long as re-transplantation to treat ATTR-PN is not planned during the study period and meets all other eligibility criteria;
  • Has sensorimotor or autonomic neuropathy not related to ATTR-PN; for example, due to autoimmune disease or monoclonal gammopathy, malignancy, or alcohol abuse;
  • Has Vitamin B-12 levels below the lower limit of normal (LLN) at Screening;
  • Has clinical evidence of untreated hyperthyroidism or hypothyroidism;
  • Has leptomeningeal TTR amyloidosis;
  • Has Type 1 diabetes;
  • Has had Type 2 diabetes for ≥5 years;
  • Has a documented case of hepatitis B or C at Screening;
  • Known history of human immunodeficiency virus (HIV) infection;
  • Has NYHA heart failure classification >Class II;
  • Had acute coronary syndrome, uncontrolled cardiac arrhythmia, or a stroke within 90 days prior to Screening;
  • Has estimated glomerular filtration rate (eGFR) by Modification of Diet for Renal Disease (MDRD) formula <30 mL/min/1.73 m2 at Screening;
  • Has abnormal liver function tests at Screening, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × upper limit of normal (ULN) or total bilirubin >3 × ULN;
  • Had a malignancy within 2 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated;
  • Has known hypersensitivity to acoramidis, its metabolites, or formulation excipients.
  • Is currently undergoing treatment for ATTR-PN with tafamidis, or patisiran, inotersen, or other knockdown agents, marketed drug products lacking a labeled indication for ATTR-PN (e.g., diflunisal, doxycycline), natural products or derivatives used as unproven therapies for ATTR-PN (e.g., green tea extract ,tauroursodeoxycholic acid [TUDCA]/ursodiol), within 14 days, or 14 days for tafamidis or 90days for patisiran and 180 days for inotersen prior to dosing.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Acoramidis HCI 800 mg (two 400mg tablets)
TTR stabilizer administered orally twice daily (BID)
Drug: Acoramidis
TTR stabilizer administered orally twice daily (BID)
Other Names:
  • AG10

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change from baseline to Month 18 in mNIS+7
Time Frame: 18 Months
To determine the efficacy of acoramidis in subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN) by evaluating the change in Modified Neuropathy Impairment Score +7 (mNIS+7) from baseline to 18 months.
18 Months
Safety: TESAEs will be used to evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic polyneuropathy (ATTR-PN)
Time Frame: 60 Months
To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)
60 Months
Safety: Adverse Events leading to treatment discontinuation will be used to evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic polyneuropathy (ATTR-PN)
Time Frame: 60 Months
To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)
60 Months
Safety: Adverse Events will be used to evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic polyneuropathy (ATTR-PN)
Time Frame: 60 Months
To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)
60 Months
Safety: Incidence of abnormal physical exam will be used to evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic polyneuropathy (ATTR-PN)
Time Frame: 60 Months
To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)
60 Months
Safety: Incidence of abnormal vital signs will be used to evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic polyneuropathy (ATTR-PN)
Time Frame: 60 Months
To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)
60 Months
Safety: Columbia-Suicide Severity Rating Scale (C-SSRS) will be used to evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic polyneuropathy (ATTR-PN)
Time Frame: 60 Months
To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)
60 Months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change from baseline to Month 18 in Norfolk QOL-DN
Time Frame: 18 Months
To evaluate the effects of acoramidis in subjects with symptomatic ATTR-PN on Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN)
18 Months
Change from baseline to Month 18 in mBMI
Time Frame: 18 Months
To evaluate the effects of acoramidis in subjects with symptomatic ATTR-PN on Modified body mass index (mBMI)
18 Months
Change from baseline to Month 18 in COMPASS-31
Time Frame: 18 Months
To evaluate the effects of acoramidis in subjects with symptomatic ATTR-PN on Composite Autonomic Score (COMPASS-31)
18 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eidos Therapeutics, a BridgeBio company

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Mark McGovern, RN, CCRN, Eidos Therapeutics, a BridgeBio company

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2021

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2026

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 29, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 6, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 12, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 9, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 26, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AG10-334

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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