NCT00409175

Brief Summary

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
128

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jan 2007

Geographic Reach
9 countries

10 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 6, 2006

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 8, 2006

Completed
24 days until next milestone

Study Start

First participant enrolled

January 1, 2007

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2009

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 1, 2009

Completed
3.6 years until next milestone

Results Posted

Study results publicly available

December 17, 2012

Completed
Last Updated

December 17, 2012

Status Verified

November 1, 2012

Enrollment Period

2.3 years

First QC Date

December 6, 2006

Results QC Date

November 16, 2012

Last Update Submit

November 16, 2012

Conditions

Familial Amyloid Polyneuropathy

Keywords

FAPFx-1006AtransthyretinTTRamyloidpolyneuropathyV30MfamilialhereditaryamyloidosisFoldRx

Outcome Measures

Primary Outcomes (2)

  • Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 18

    Response to treatment was indicated by either improvement (decrease from baseline) or stabilization (change from baseline of 0 to less than\[\<\] 2) in NIS-LL score, based on mean of 2 scores in 1 week period. NIS-LL: assessed muscle weakness, reflexes, sensation. Each item scored separately for left, right limbs. Components of muscle weakness scored on 0(normal) to 4(paralysis) scale, higher score=greater weakness. Components of reflexes, sensation scored 0=normal, 1=decreased, or 2=absent. Total NIS-LL score range 0-88, higher score=greater impairment.

    Month 18

  • Change From Baseline in Norfolk Quality of Life- Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 18

    Norfolk QOL-DN: 35-item participant-rated questionnaire used to assess impact of diabetic neuropathy on the quality of life of participants with diabetic neuropathy; Item 1 to 7: related to symptoms and presence of symptom was assessed as 1 and absence was assessed as 0. Item 8-35: related to activities of daily living and scored on a 5-point Likert scale, where 0= no problem and 4= severe problem (except item 32, where -2= much better, 0=about the same, 2=much worse). TQOL= sum of all the items, total possible score range= -2 to 138, where higher score=worse quality of life.

    Baseline, Month 18

Secondary Outcomes (8)

  • Change From Baseline in Neuropathy Impairment Score- Lower Limb (NIS-LL) Score at Month 6, 12 and 18

    Baseline, Month 6, 12, 18

  • Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 6 and 12

    Month 6, 12

  • Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 6 and 12

    Baseline, Month 6, 12

  • Change From Baseline in Norfolk Quality of Life - Diabetic Neuropathy (QOL-DN) Domain Scores at Month 6, 12 and 18

    Baseline, Month 6, 12, 18

  • Change From Baseline in Summated 7 Score for Large Nerve Fiber Function at Month 6, 12 and 18

    Baseline, Month 6, 12, 18

  • +3 more secondary outcomes

Study Arms (2)

1.

EXPERIMENTAL

Fx-1006A

Drug: Fx-1006A

2.

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Fx-1006ADRUG

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

1.
PlaceboDRUG

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

2.

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Amyloid documented by biopsy.
  • Documented V30M TTR mutation.
  • Peripheral and/or autonomic neuropathy with a Karnofsky Performance Status ≥50.
  • Patient is 18-75 years old.
  • 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.
  • Patient is, in the opinion of the investigator, willing and able to comply with the study medication regimen and all other study requirements.

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (10)

MGH Neuropathy Laboratory

Boston, Massachusetts, 02114, United States

Location

FLENI-Hepatology and Organ Transplant Dept.

Ciudad de Buenos Aires, Buenos Aires, C1428AQK, Argentina

Location

Hospital Universitário Prof. Clementino Fraga Filho-UFRJ

Rio de Janeiro, Southeast, Cep 21945-560, Brazil

Location

CHU de Bicetre

Le Kremlin-Bicêtre, Île-de-France Region, 94275, France

Location

Universitatsklinikum Munster, Transplant Hepatology

Münster, North Rhine-Westphalia, 48149, Germany

Location

Serviço de Neurologia-Hospital de Santa Maria

Lisbon, Lisbon District, 1649-035, Portugal

Location

Unidade Clinica de Paramiloidose-Hospital Santo Antonio

Porto, Norte, 4099-001, Portugal

Location

Hospital Clinic de Barcelona

Barcelona, Catalonia, 08036, Spain

Location

Umea University Hospital

Umeå, Västerbotten County, SE-901 85, Sweden

Location

Kings College Hospital

London, London, SE5 9RS, United Kingdom

Location

Related Publications (6)

  • 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.

    PMID: 32107748DERIVED

  • 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.

    PMID: 31353964DERIVED

  • 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.

    PMID: 30558645DERIVED

  • 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.

    PMID: 29115008DERIVED

  • 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.

    PMID: 28393570DERIVED

  • 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.

    PMID: 27494299DERIVED

Related Links

MeSH Terms

Conditions

Amyloid Neuropathies, FamilialAlzheimer DiseasePolyneuropathiesAmyloidosis

Interventions

tafamidis

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesNervous System DiseasesAmyloid NeuropathiesPeripheral Nervous System DiseasesNeuromuscular DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesAmyloidosis, FamilialMetabolism, Inborn ErrorsMetabolic DiseasesNutritional and Metabolic DiseasesProteostasis DeficienciesDementiaBrain DiseasesCentral Nervous System DiseasesTauopathiesNeurocognitive DisordersMental Disorders

Limitations and Caveats

Instead of the intended endpoint 'heat pain and cooling threshold', results of 'summated 3 score for small nerve fiber function' were reported.

Results Point of Contact

Title
Pfizer ClinicalTrials.gov Call Center
Organization
Pfizer, Inc.
ClinicalTrials.gov_Inquiries@pfizer.com
1-800-718-1021

Study Officials

  • Jeff Packman

    FoldRx Pharmaceuticals, Inc.

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 6, 2006

First Posted

December 8, 2006

Study Start

January 1, 2007

Primary Completion

May 1, 2009

Study Completion

May 1, 2009

Last Updated

December 17, 2012

Results First Posted

December 17, 2012

Record last verified: 2012-11

Locations

PT(2)US(1)DE(1)ES(1)AR(1)BR(1)FR(1)SE(1)GB(1)