Transthyretin-Related (ATTR) Familial Amyloid PolyneuropathyPhase 3ATTRibute-PNNCT04418024
Efficacy and Safety of AG10 in Subjects with Transthyretin Amyloid Polyneurophathy
A Phase 3 study testing AG10 in people with Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy, run by Eidos Therapeutics, a BridgeBio company at 1 site in United States.
Trial summary
See updated study design under NCT04882735. Phase 3 efficacy and safety of AG10 compared with placebo 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?
- AG10
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Oct 2020to 30 Apr 2024
- 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
- Be male or female ≥18 to ≤90 years of age;
- Have Stage I or II symptoms (polyneuropathy disability [PND] ≤IIIa) of ATTR-PN and an established diagnosis of ATTR-PN as defined by physical exam 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 randomization. *No genetic testing is needed for subjects who are recipients of domino liver transplants;
- Have an anticipated survival of ≥2 years
- 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, autoimmune disease or monoclonal gammopathy, malignancy, or alcohol abuse;
- Has Vitamin B-12 levels below the lower limit of normal (LLN);
- Has clinical evidence of untreated hyper/hypothyroidism;
- Has leptomeningeal TTR amyloidosis;
Show all 12Show fewer
- Has Type 1 diabetes;
- Has had Type 2 diabetes for ≥5 years;
- Has active hepatitis B or C or known human immunodeficiency virus (HIV) infection;
- Has NYHA heart failure classification >Class II
- Had a malignancy within 2 years, except for basal or squamous cell carcinoma of
- Is currently undergoing treatment for ATTR-PN with patisiran, inotersen, or other gene silencing agents, marketed drug products lacking a label 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 90 days for patisiran and 180 days for inotersen prior to dosing. Prior to screening, tafamidis, if already prescribed to potential subjects as part of their established background therapy, is allowed at the labeled dosage and administration of 20 mg/day for the treatment of ATTR-PN with, i in the opinion of the Investigator, evidence of disease progression while on tafamidis treatment
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of AG10 in Subjects with Symptomatic Transthyretin Amyloid Polyneuropathy (ATTRibute-PN Trial)
See updated study design under NCT04882735. Phase 3 efficacy and safety of AG10 compared with placebo in subjects with symptomatic Transthyretin Amyloid Polyneuropathy (ATTR-PN)
Read the detailed description
See updated study design under ClinicalTrials.gov Identifier NCT04882735.
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 is researching the investigational drug AG10 800mg (2 tablets) administered orally twice a day. Through the study, Eidos wants to evaluate the efficacy and safety of AG10 in patients with ATTR-PN versus placebo.
This is an 18 month, placebo-controlled study. This means that, during the 18 month study, investigators conducting the research and study participants will not know whether the study participant is receiving AG10 or placebo.
The primary outcome of the study is the difference between AG10 and placebo groups in the Modified Neurologic Impairment Score +7 (mNIS+7) at 18 months of treatment versus baseline.
At the end of 18 months, participants may be eligible to receive investigational AG10, and there is no placebo. This is called an "open label extension." This part of the study may help us better understand the safety related to taking AG10 over a longer period of time.
- Being tested
- AG10, Placebo
- 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.
AG10Drug
Also called Oral AG10
TTR stabilizer administered orally twice daily (BID)
PlaceboDrug
Also called Placebo Oral Tablet
Non-active control
| Study group | Role | What they receive |
|---|---|---|
| AG10 800 mg | Experimental | TTR stabilizer administered orally twice daily (BID) Receives: Drug: AG10 |
| Placebo | Placebo comparator | Placebo administered orally twice daily (BID) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline to Month 18 of treatment in Modified Neuropathy Impairment
Evaluate the difference between the AG10 and placebo groups in Modified Neuropathy Impairment which is a composite scale that asses,in part, muscle weakness, sensory loss, and decreased muscle stretch reflexes. It is calculated on a scale of 0 to 304 with higher scores indicating a worsening of the disease.
Measured: 18 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2020
- Study start21 Oct 2020
- Primary completion31 Mar 2024 (estimated)
- Study completion30 Apr 2024 (estimated)
Why it stopped: After a careful review of the currently available treatments worldwide for patients with ATTR-polyneuropathy, Eidos has made the decision to halt the current study design.
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eidos Therapeutics, a BridgeBio company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mark McGovern, RN, CCRN, Study director, Eidos Therapeutics, a BridgeBio company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04418024
- Sponsor's protocol ID
- AG10-333
- Other IDs
- 2018-004670-10, 2018
- Acronym
- ATTRibute-PN
- Status last verified
- Jun 2021
- First submitted
- 22 May 2020
- Last updated
- 19 Sep 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of AG10 in Subjects with Symptomatic Transthyretin Amyloid Polyneuropathy (ATTRibute-PN Trial)
- ClinicalTrials.gov ID
- NCT04418024
- Acronym / sponsor ID
- ATTRibute-PN / AG10-333
- Keywords
- TTR, ATTR-PN, Familial ATTR-PN, Amyloidosis, Amyloid, Transthyretin, Polyneuropathy, TTR-mediated amyloidosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: After a careful review of the currently available treatments worldwide for patients with ATTR-polyneuropathy, Eidos has made the decision to halt the current study design.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Eidos Therapeutics, a BridgeBio companyIndustry (pharma, biotech, devices)
- Study start
- 21 Oct 2020 (actual)
- Primary completion
- 31 Mar 2024 (estimated)
- Study completion
- 30 Apr 2024 (estimated)
- First posted
- 5 Jun 2020 (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.
See updated study design under NCT04882735. Phase 3 efficacy and safety of AG10 compared with placebo in subjects with symptomatic Transthyretin Amyloid Polyneuropathy (ATTR-PN)
Detailed description
See updated study design under ClinicalTrials.gov Identifier NCT04882735.
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 is researching the investigational drug AG10 800mg (2 tablets) administered orally twice a day. Through the study, Eidos wants to evaluate the efficacy and safety of AG10 in patients with ATTR-PN versus placebo.
This is an 18 month, placebo-controlled study. This means that, during the 18 month study, investigators conducting the research and study participants will not know whether the study participant is receiving AG10 or placebo.
The primary outcome of the study is the difference between AG10 and placebo groups in the Modified Neurologic Impairment Score +7 (mNIS+7) at 18 months of treatment versus baseline.
At the end of 18 months, participants may be eligible to receive investigational AG10, and there is no placebo. This is called an "open label extension." This part of the study may help us better understand the safety related to taking AG10 over a longer period of time.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AG10 800 mg | Experimental | Drug: AG10TTR stabilizer administered orally twice daily (BID) |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo 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)
- Be male or female ≥18 to ≤90 years of age;
- Have Stage I or II symptoms (polyneuropathy disability [PND] ≤IIIa) of ATTR-PN and an established diagnosis of ATTR-PN as defined by physical exam 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 randomization. *No genetic testing is needed for subjects who are recipients of domino liver transplants;
Key exclusion criteria (12 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, autoimmune disease or monoclonal gammopathy, malignancy, or alcohol abuse;
- Has Vitamin B-12 levels below the lower limit of normal (LLN);
- Has clinical evidence of untreated hyper/hypothyroidism;
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 |
|---|---|---|
| AG10Also: Oral AG10TTR stabilizer administered orally twice daily (BID) | Drug | AG10 800 mg |
| PlaceboAlso: Placebo Oral TabletNon-active control | Drug | Placebo |
Primary outcome
Change from baseline to Month 18 of treatment in Modified Neuropathy Impairment
Time frame: 18 Months
Evaluate the difference between the AG10 and placebo groups in Modified Neuropathy Impairment which is a composite scale that asses,in part, muscle weakness, sensory loss, and decreased muscle stretch reflexes. It is calculated on a scale of 0 to 304 with higher scores indicating a worsening of the disease.
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.
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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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AG10 in people with Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy, run by Eidos Therapeutics, a BridgeBio company at 1 site in United States.
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 12 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.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 of treatment in Modified Neuropathy Impairment (time frame: 18 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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.