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

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ClinicalTrials.gov Identifier: NCT04418024
Recruitment Status : Recruiting
First Posted : June 5, 2020
Last Update Posted : November 19, 2020
Sponsor:
Information provided by (Responsible Party):
Eidos Therapeutics

Brief Summary:
Phase 3 efficacy and safety of AG10 compared with placebo in subjects with symptomatic Transthyretin Amyloid Polyneuropathy (ATTR-PN)

Condition or disease Intervention/treatment Phase
Transthyretin-Related (ATTR) Familial Amyloid Polyneuropathy Drug: AG10 Drug: Placebo Phase 3

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 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 145 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : October 21, 2020
Estimated Primary Completion Date : March 31, 2024
Estimated Study Completion Date : April 30, 2024


Arm Intervention/treatment
Experimental: AG10 800 mg
TTR stabilizer administered orally twice daily (BID)
Drug: AG10
TTR stabilizer administered orally twice daily (BID)
Other Name: Oral AG10

Placebo Comparator: Placebo
Placebo administered orally twice daily (BID)
Drug: Placebo
Non-active control
Other Name: Placebo Oral Tablet




Primary Outcome Measures :
  1. 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.



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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04418024


Contacts
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Contact: Mark McGovern, RN, CCRN +1415-887-1471 medinfo@eidostx.com

Locations
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United States, California
Eidos Therapeutics Not yet recruiting
San Francisco, California, United States, 94104
Contact: Mark McGovern, RN. CCRN         
Canada, British Columbia
Vancouver General Hospital Recruiting
Vancouver, British Columbia, Canada, V5Z 1M9
Contact: Deborah Kraus       deborah.kraus@vch.ca   
Principal Investigator: Michelle Mezei         
Spain
Hospital Son Llàtzer Recruiting
Palma de Mallorca, Balearic Islands, Spain, 07198
Contact: Maria Eugenia Cisneros Barroso    +34 871 20 20 32    maria.cisneros@hsll.es   
Contact: Adrian Rodriguez Rodriguez       adrian.rodriguez@hsll.es   
Principal Investigator: Juan Gonzalez Moreno         
Sponsors and Collaborators
Eidos Therapeutics
Investigators
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Study Director: Mark McGovern, RN, CCRN Eidos Therapeutics
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Responsible Party: Eidos Therapeutics
ClinicalTrials.gov Identifier: NCT04418024    
Other Study ID Numbers: AG10-333
2018-004670-10 ( EudraCT Number )
First Posted: June 5, 2020    Key Record Dates
Last Update Posted: November 19, 2020
Last Verified: November 2020

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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
Keywords provided by Eidos Therapeutics:
TTR
ATTR-PN
Familial ATTR-PN
Amyloidosis
Amyloid
Transthyretin
Polyneuropathy
TTR-mediated amyloidosis
Amyloidosis, hereditary
Familial Amyloid Polyneuropathies
Amyloidosis, Hereditary, Transthyretin-Related
Additional relevant MeSH terms:
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Polyneuropathies
Amyloid Neuropathies
Amyloid Neuropathies, Familial
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Amyloidosis, Familial
Metabolism, Inborn Errors