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

Primary Purpose

Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy

Status
Withdrawn
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
AG10
Placebo
Sponsored by
Eidos Therapeutics, a BridgeBio company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy focused on measuring TTR, ATTR-PN, Familial ATTR-PN, Amyloidosis, Amyloid, Transthyretin, Polyneuropathy, TTR-mediated amyloidosis, Amyloidosis, hereditary, Familial Amyloid Polyneuropathies, Amyloidosis, Hereditary, Transthyretin-Related

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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 %;

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, 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;
  • 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

Sites / Locations

  • Eidos Therapeutics

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

AG10 800 mg

Placebo

Arm Description

TTR stabilizer administered orally twice daily (BID)

Placebo administered orally twice daily (BID)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
May 22, 2020
Last Updated
June 11, 2021
Sponsor
Eidos Therapeutics, a BridgeBio company
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1. Study Identification

Unique Protocol Identification Number
NCT04418024
Brief Title
Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Polyneurophathy
Acronym
ATTRibute-PN
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Withdrawn
Why 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.
Study Start Date
October 21, 2020 (Actual)
Primary Completion Date
March 31, 2024 (Anticipated)
Study Completion Date
April 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Eidos Therapeutics, a BridgeBio company

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief 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)
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy
Keywords
TTR, ATTR-PN, Familial ATTR-PN, Amyloidosis, Amyloid, Transthyretin, Polyneuropathy, TTR-mediated amyloidosis, Amyloidosis, hereditary, Familial Amyloid Polyneuropathies, Amyloidosis, Hereditary, Transthyretin-Related

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
AG10 800 mg
Arm Type
Experimental
Arm Description
TTR stabilizer administered orally twice daily (BID)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo administered orally twice daily (BID)
Intervention Type
Drug
Intervention Name(s)
AG10
Other Intervention Name(s)
Oral AG10
Intervention Description
TTR stabilizer administered orally twice daily (BID)
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo Oral Tablet
Intervention Description
Non-active control
Primary Outcome Measure Information:
Title
Change from baseline to Month 18 of treatment in Modified Neuropathy Impairment
Description
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.
Time Frame
18 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 %; 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, 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; 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mark McGovern, RN, CCRN
Organizational Affiliation
Eidos Therapeutics, a BridgeBio company
Official's Role
Study Director
Facility Information:
Facility Name
Eidos Therapeutics
City
San Francisco
State/Province
California
ZIP/Postal Code
94104
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Efficacy and Safety of AG10 in Subjects With Transthyretin Amyloid Polyneurophathy

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