NCT00409175

Safety and Efficacy of Orally Administered Fx-1006A in Patients With Familial Amyloid Polyneuropathy (FAP): A Randomized, Double-blind, Placebo-controlled Study

Completed Phase 2/Phase 3 Results posted Last updated 16 November 2012

What this trial tests

Phase 2/Phase 3 trial testing Fx-1006A in Familial Amyloid Polyneuropathy in 128 participants. Completed in 1 May 2009.

Timeline

1 January 2007

Primary endpoint
1 May 2009

1 May 2009

Quick facts

Lead sponsor	Pfizer
Phase	Phase 2/Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	128
Start date	1 January 2007
Primary completion	1 May 2009
Estimated completion	1 May 2009
Sites	10 locations across United States, Argentina, Brazil, France, Germany, Portugal, Spain, Sweden

Drugs / interventions tested

• Fx-1006A — full drug profile →
• Placebo

Conditions studied

• Familial Amyloid Polyneuropathy — all drugs for Familial Amyloid Polyneuropathy →

Sponsor

Pfizer — full company profile →

Who can join

Adults 18 to 75, any sex, with Familial Amyloid Polyneuropathy. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Percentage of Participants With Response to Treatment as Measured by Neuropathy Impairment Score - Lower Limb (NIS-LL) at Month 18
  Time frame: 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 scor
• Change From Baseline in Norfolk Quality of Life- Diabetic Neuropathy (QOL-DN) Total Quality of Life (TQOL) Score at Month 18
  Time frame: Baseline, 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

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial.
   Coelho T, Maia LF, Martins da Silva A, Waddington Cruz M, et al · · 2012 · cited 580× · PMID 22843282 · DOI 10.1212/wnl.0b013e3182661eb1
2. Early intervention with tafamidis provides long-term (5.5-year) delay of neurologic progression in transthyretin hereditary amyloid polyneuropathy.
   Waddington Cruz M, Amass L, Keohane D, Schwartz J, et al · · 2016 · cited 71× · PMID 27494299 · DOI 10.1080/13506129.2016.1207163
3. Advances in the treatment of hereditary transthyretin amyloidosis: A review.
   Gertz MA, Mauermann ML, Grogan M, Coelho T. · · 2019 · cited 66× · PMID 31368669 · DOI 10.1002/brb3.1371
4. Predictive model of response to tafamidis in hereditary ATTR polyneuropathy.
   Monteiro C, Mesgazardeh JS, Anselmo J, Fernandes J, et al · · 2019 · cited 57× · PMID 31217346 · DOI 10.1172/jci.insight.126526
5. Amyloidosis-the Diagnosis and Treatment of an Underdiagnosed Disease.
   Ihne S, Morbach C, Sommer C, Geier A, et al · · 2020 · cited 50× · PMID 32295695 · DOI 10.3238/arztebl.2020.0159
6. Treatment of Transthyretin Amyloid Cardiomyopathy: The Current Options, the Future, and the Challenges.
   Tschöpe C, Elsanhoury A. · · 2022 · cited 43× · PMID 35456241 · DOI 10.3390/jcm11082148
7. Tafamidis delays disease progression in patients with early stage transthyretin familial amyloid polyneuropathy: additional supportive analyses from the pivotal trial.
   Keohane D, Schwartz J, Gundapaneni B, Stewart M, et al · · 2017 · cited 43× · PMID 28393570 · DOI 10.1080/13506129.2017.1301419
8. Drug Discovery and Development in Rare Diseases: Taking a Closer Look at the Tafamidis Story.
   Burton A, Castaño A, Bruno M, Riley S, et al · · 2021 · cited 37× · PMID 33776421 · DOI 10.2147/dddt.s289772