Transthyretin-Related (ATTR) Familial Amyloid PolyneuropathyPhase 3NCT04882735

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

A Phase 3 study testing Acoramidis in people with Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy, run by Eidos Therapeutics, a BridgeBio company.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record

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Trial summary

Phase 3 efficacy and safety of acoramidis in subjects with symptomatic Transthyretin Amyloid Polyneuropathy (ATTR-PN) Read more about this study

Who is it for?: Ages 18 to 90 years
Conditions the study is for: Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy
What is being tested?: Acoramidis
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 0 participants
Where: No sites listed yet
Study dates: 8 Sep 2021to Oct 2026
Phase: Phase 3
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 90 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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 %.

Who cannot join

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;

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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.

About this study

Official title: 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)

Read the 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.

Conditions: Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy
Being tested: Acoramidis
Keywords: TTR, ATTR-PN, Familial ATTR-PN, Amyloidosis, Amyloid, Transthyretin, Polyneuropathy, TTR-mediated amyloidosis, Amyloidosis, hereditary, Familial Amyloid Polyneuropathies, Amyloidosis, Hereditary, Transthyretin-Related
Medical subject headings: Amyloid Neuropathies, Familial, Amyloidosis, Alzheimer Disease, Polyneuropathies, Amyloidosis, Familial, Amyloidosis, Hereditary, Transthyretin-Related

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AcoramidisDrug
Also called AG10
TTR stabilizer administered orally twice daily (BID)

Study groups in NCT04882735
Study group	Role	What they receive
Acoramidis HCI 800 mg (two 400mg tablets)	Experimental	TTR stabilizer administered orally twice daily (BID) Receives: Drug: Acoramidis

What is being measured

The primary outcome is the main question the study is designed to answer.

Change from baseline to Month 18 in mNIS+7
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.
Measured: 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)
To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)
Measured: 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)
To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)
Measured: 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)
To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)
Measured: 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)
To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)
Measured: 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)
To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)
Measured: 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)
To evaluate the long-term safety and tolerability of acoramidis administered to subjects with symptomatic transthyretin amyloid polyneuropathy (ATTR-PN)
Measured: 60 Months

Secondary outcomes (3)

Change from baseline to Month 18 in Norfolk QOL-DN
To evaluate the effects of acoramidis in subjects with symptomatic ATTR-PN on Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QOL-DN)
Measured: 18 Months
Change from baseline to Month 18 in mBMI
To evaluate the effects of acoramidis in subjects with symptomatic ATTR-PN on Modified body mass index (mBMI)
Measured: 18 Months
Change from baseline to Month 18 in COMPASS-31
To evaluate the effects of acoramidis in subjects with symptomatic ATTR-PN on Composite Autonomic Score (COMPASS-31)
Measured: 18 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

8 Sep 2021Oct 2026

First posted12 May 2021
Study start8 Sep 2021
Primary completionSep 2026 (estimated)
Study completionOct 2026 (estimated)

Why it stopped: Sponsor's decision to cancel study

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Transthyretin-Related (ATTR) Familial Amyloid PolyneuropathyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 0 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04882735
Sponsor's protocol ID: AG10-334
Status last verified: Jan 2022
First submitted: 29 Apr 2021
Last updated: 19 Sep 2024
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Active, not recruitingPhase 3
A Phase 3 Study of NTLA-2001 in ATTRv-PN
Neuromuscular Disease, Neuromuscular Diseases (NMD)
RecruitingPhase 3
MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)
Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
Active, not recruitingPhase 3
HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
Enrolling by invitationPhase 3
A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
Active, not recruitingObservational study
Observational Study of Neurofilament Light Chain (NfL) as a Biomarker in Asymptomatic Carriers of the Transthyretin (TTR) Variants and Patients With Hereditary Transthyretin-mediated (hATTR) Amyloidosis With Polyneuropathy
Hereditary Amyloidosis, Transthyretin-Related, Asymptomatic Carrier State

All Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: 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)
ClinicalTrials.gov ID: NCT04882735
Acronym / sponsor ID: AG10-334
Conditions: Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy
Keywords: TTR, ATTR-PN, Familial ATTR-PN, Amyloidosis, Amyloid, Transthyretin, Polyneuropathy, TTR-mediated amyloidosis
Phase: Phase 3
Study type: Interventional
Recruitment status: WithdrawnReason stopped: Sponsor's decision to cancel study
Enrolment: 0 participants (actual)
Lead sponsor: Eidos Therapeutics, a BridgeBio companyIndustry (pharma, biotech, devices)
Study start: 8 Sep 2021 (actual)
Primary completion: Sep 2026 (estimated)
Study completion: Oct 2026 (estimated)
First posted: 12 May 2021 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Detailed description

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 design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Acoramidis HCI 800 mg (two 400mg tablets)	Experimental	Drug: AcoramidisTTR stabilizer administered orally twice daily (BID)

Who may qualify

Ages: 18 to 90 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

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;

Key exclusion criteria (16 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
AcoramidisAlso: AG10TTR stabilizer administered orally twice daily (BID)	Drug	Acoramidis HCI 800 mg (two 400mg tablets)

Primary outcome

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.
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)
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)
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)
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)
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)
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)

3 secondary outcomes

Change from baseline to Month 18 in Norfolk QOL-DN
Time frame: 18 Months
Change from baseline to Month 18 in mBMI
Time frame: 18 Months
Change from baseline to Month 18 in COMPASS-31
Time frame: 18 Months

Results and safety

The study was withdrawn before enrolling participants, so there are no results.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Sep 2024.
Individual participant dataSharing planned: No

Related trials for Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy

Active, not recruitingPhase 3
A Phase 3 Study of NTLA-2001 in ATTRv-PN
Neuromuscular Disease, Neuromuscular Diseases (NMD)
RecruitingPhase 3
MAGNITUDE: A Phase 3 Study of NTLA-2001 in Participants With Transthyretin Amyloidosis With Cardiomyopathy (ATTR-CM)
Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
Active, not recruitingPhase 3
HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
Enrolling by invitationPhase 3
A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy
Transthyretin Amyloidosis (ATTR) With Cardiomyopathy
Active, not recruitingObservational study
Observational Study of Neurofilament Light Chain (NfL) as a Biomarker in Asymptomatic Carriers of the Transthyretin (TTR) Variants and Patients With Hereditary Transthyretin-mediated (hATTR) Amyloidosis With Polyneuropathy
Hereditary Amyloidosis, Transthyretin-Related, Asymptomatic Carrier State

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Mark McGovern, RN, CCRN study director

Eidos Therapeutics, a BridgeBio company

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Acoramidis in people with Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy, run by Eidos Therapeutics, a BridgeBio company.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change from baseline to Month 18 in mNIS+7 (time frame: 18 Months). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04882735.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.