Safety and Efficacy Study of Fx-1006A in Patients With Familial Amyloidosis

NCT ID: NCT00409175

Last Updated: 2012-12-17

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

128 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-01-31

Study Completion Date

2009-05-31

Brief Summary

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This study will examine whether Fx-1006A is effective in halting the progression of Familial Amyloid Polyneuropathy (FAP).

Deposition of TTR amyloid is associated with a variety of human diseases. Deposition of amyloid fibrils of variant TTR (primarily V30M) in peripheral nerve tissue produces the condition called FAP.

The prevention of the formation of amyloid by stabilization of the TTR native state should constitute an effective therapy for amyloid diseases. Therapeutic intervention with a TTR stabilizer drug, such as Fx-1006A, is hypothesized to stop progression of the disease in FAP patients. FAP is a uniformly fatal disease and Fx-1006A is intended to halt the relentless neurological deterioration FAP patients experience.

This Phase 2/3 study will enroll early to mid-stage FAP patients in order to interrupt and stabilize the disease at a point in time where progression of motor and autonomic dysfunction can be maximally effected. Male and female patients with FAP with documented V30M TTR mutation will receive Fx-1006A or placebo once daily for a period of eighteen (18) months.

Detailed Description

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Deposition of TTR amyloid is associated with a variety of human diseases. Deposition of amyloid fibrils of variant TTR (primarily V30M) in peripheral nerve tissue produces the condition called FAP.

The prevention of the formation of amyloid by stabilization of the TTR native state should constitute an effective therapy for amyloid diseases. Therapeutic intervention with a TTR stabilizer drug, such as Fx-1006A, is hypothesized to stop progression of the disease in FAP patients. FAP is a uniformly fatal disease and Fx-1006A is intended to halt the relentless neurological deterioration FAP patients experience.

This Phase 2/3 study will enroll early to mid-stage FAP patients in order to interrupt and stabilize the disease at a point in time where progression of motor and autonomic dysfunction can be maximally effected. Male and female patients with FAP with documented V30M TTR mutation will receive Fx-1006A or placebo once daily for a period of eighteen (18) months.

Conditions

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Familial Amyloid Polyneuropathy

Keywords

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FAP Fx-1006A transthyretin TTR amyloid polyneuropathy V30M familial hereditary amyloidosis FoldRx

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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1.

Fx-1006A

Group Type EXPERIMENTAL

Fx-1006A

Intervention Type DRUG

Fx-1006A 20mg or matched placebo once daily (at the same time each day) for a period of 18 Months

2.

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Fx-1006A 20mg or matched placebo once daily (at the same time each day) for a period of 18 Months

Interventions

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Fx-1006A

Fx-1006A 20mg or matched placebo once daily (at the same time each day) for a period of 18 Months

Intervention Type DRUG

Placebo

Fx-1006A 20mg or matched placebo once daily (at the same time each day) for a period of 18 Months

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Amyloid documented by biopsy.
2. Documented V30M TTR mutation.
3. Peripheral and/or autonomic neuropathy with a Karnofsky Performance Status ≥50.
4. Patient is 18-75 years old.
5. If female, patient is post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control. If male with a female partner of childbearing potential, willing to use an acceptable method of birth control for the duration of the study. For both females and males, birth control must be used for at least 3 months after the last dose of study medication.
6. Patient is, in the opinion of the investigator, willing and able to comply with the study medication regimen and all other study requirements.

Exclusion Criteria

1. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs).
2. Primary amyloidosis.
3. If female, patient is pregnant or breast feeding.
4. Prior liver transplantation.
5. No recordable sensory threshold for vibration perception in both feet, as measured by CASE IV.
6. Positive results for hepatitis B surface antigen (HBsAg), anti-hepatitis C virus (HCV), and/or human immunodeficiency virus (HIV).
7. Renal insufficiency or liver function test abnormalities.
8. New York Heart Association (NYHA) Functional Classification ≥III.
9. Other causes of sensorimotor neuropathy (B12 deficiency, Diabetes Mellitus, HIV treated with retroviral medications, thyroid disorders, alcohol abuse, and chronic inflammatory diseases).
10. Co-morbidity anticipated to limit survival to less than 18 months.
11. Patient received an investigational drug/device and/or participated in another clinical investigational study within 60 days before Baseline.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jeff Packman

Role: STUDY_DIRECTOR

FoldRx Pharmaceuticals, Inc.

Locations

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MGH Neuropathy Laboratory

Boston, Massachusetts, United States

Site Status

FLENI-Hepatology and Organ Transplant Dept.

Ciudad de Buenos Aires, Buenos Aires, Argentina

Site Status

Hospital Universitário Prof. Clementino Fraga Filho-UFRJ

Rio de Janeiro, Southeast, Brazil

Site Status

CHU de Bicetre

Le Kremlin-Bicêtre, Île-de-France Region, France

Site Status

Universitatsklinikum Munster, Transplant Hepatology

Münster, North Rhine-Westphalia, Germany

Site Status

Serviço de Neurologia-Hospital de Santa Maria

Lisbon, Lisbon District, Portugal

Site Status

Unidade Clinica de Paramiloidose-Hospital Santo Antonio

Porto, Norte, Portugal

Site Status

Hospital Clinic de Barcelona

Barcelona, Catalonia, Spain

Site Status

Umea University Hospital

Umeå, Västerbotten County, Sweden

Site Status

Kings College Hospital

London, London, United Kingdom

Site Status

Countries

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United States Argentina Brazil France Germany Portugal Spain Sweden United Kingdom

References

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Merlini G, Coelho T, Waddington Cruz M, Li H, Stewart M, Ebede B. Evaluation of Mortality During Long-Term Treatment with Tafamidis for Transthyretin Amyloidosis with Polyneuropathy: Clinical Trial Results up to 8.5 Years. Neurol Ther. 2020 Jun;9(1):105-115. doi: 10.1007/s40120-020-00180-w. Epub 2020 Feb 27.

Reference Type DERIVED
PMID: 32107748 (View on PubMed)

Huber P, Flynn A, Sultan MB, Li H, Rill D, Ebede B, Gundapaneni B, Schwartz JH. A comprehensive safety profile of tafamidis in patients with transthyretin amyloid polyneuropathy. Amyloid. 2019 Dec;26(4):203-209. doi: 10.1080/13506129.2019.1643714. Epub 2019 Jul 27.

Reference Type DERIVED
PMID: 31353964 (View on PubMed)

Amass L, Li H, Gundapaneni BK, Schwartz JH, Keohane DJ. Influence of baseline neurologic severity on disease progression and the associated disease-modifying effects of tafamidis in patients with transthyretin amyloid polyneuropathy. Orphanet J Rare Dis. 2018 Dec 17;13(1):225. doi: 10.1186/s13023-018-0947-7.

Reference Type DERIVED
PMID: 30558645 (View on PubMed)

Gundapaneni BK, Sultan MB, Keohane DJ, Schwartz JH. Tafamidis delays neurological progression comparably across Val30Met and non-Val30Met genotypes in transthyretin familial amyloid polyneuropathy. Eur J Neurol. 2018 Mar;25(3):464-468. doi: 10.1111/ene.13510. Epub 2017 Dec 26.

Reference Type DERIVED
PMID: 29115008 (View on PubMed)

Keohane D, Schwartz J, Gundapaneni B, Stewart M, Amass L. Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial. Amyloid. 2017 Mar;24(1):30-36. doi: 10.1080/13506129.2017.1301419. Epub 2017 Apr 10.

Reference Type DERIVED
PMID: 28393570 (View on PubMed)

Waddington Cruz M, Amass L, Keohane D, Schwartz J, Li H, Gundapaneni B. Early intervention with tafamidis provides long-term (5.5-year) delay of neurologic progression in transthyretin hereditary amyloid polyneuropathy. Amyloid. 2016 Sep;23(3):178-183. doi: 10.1080/13506129.2016.1207163. Epub 2016 Aug 5.

Reference Type DERIVED
PMID: 27494299 (View on PubMed)

Related Links

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http://www.emedicine.com/med/topic3365.htm

Amyloidosis, Transthyretin-Related

Other Identifiers

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B3461020

Identifier Type: -

Identifier Source: secondary_id

FX-005

Identifier Type: -

Identifier Source: org_study_id