An Extension of Study Fx-005 Evaluating Long-Term Safety And Clinical Outcomes Of Fx-1006A In Patients With Transthyretin Amyloid Polyneuropathy

NCT ID: NCT00791492

Last Updated: 2012-12-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2010-10-31

Brief Summary

This study is designed to determine the long-term safety and tolerability of Fx-1006A as well as the effects of Fx-1006A on clinical outcomes in patients with ATTR-PN.

All patients who enroll in this extension study will receive once-daily oral 20 mg Fx-1006A for 12 months; therefore, patients randomized to placebo in Study Fx-005 will cross over to active drug (Fx-1006A 20 mg) during this study. However, patients and their families as well as clinical Investigators and their clinical site staff will remain blinded to the original Fx-005 treatment assignment. It is intended that there will be no interruption in study medication administration between the two studies. The majority of safety and clinical outcomes assessments will be identical to those evaluated in Study Fx-005. Additional assessments for this open-label extension study include 24-hour Holter monitoring and skin biopsy for IENF; patients will be required to provide written informed consent to participate in this open-label extension study prior to having these additional procedures performed.

The values obtained from procedures and evaluations conducted during the Month 18 visit of Study Fx-005 will be used as the Baseline values for this open-label extension study. The Baseline assessments of IENF and Holter monitoring may be conducted at either day of the Month 18 visit days of Study Fx-005, but prior to the first Fx-1006A dose in this open-label extension study. Clinic Visits will be conducted at Week 6 (± 2 days), and Month 3 (± 1 week), Month 6 (± 2 weeks), and Month 12 (± 2 weeks). Monthly telephone contacts (± 1 week of the scheduled date) will be made during months in which no investigative site visits are scheduled (Months 2, 4, 5, 7, 8, 9, 10, and 11) for assessment of adverse events and concomitant medications.

Neurological evaluation by NIS-LL will be performed at Months 6 and 12. The NIS-LL will be assessed by utilizing the average of two successive NIS-LL clinical assessment scores obtained at least 24 hours apart within a one week period for each study visit. A dedicated neurologist will be required to perform NIS-LL scoring across all time-points for each individual patient enrolled in the study.

Quality of life utilizing the Norfolk QOL-DN will be assessed at Months 6 and 12 (based on the total score as well as the five individual domains of the questionnaire).

QST (utilizing CASE IV), NCS, HRDB, mBMI, and echocardiography will be conducted at Months 6 and 12. Holter monitoring will be conducted at Baseline and Months 6 and 12. Biopsies for IENF will be obtained at Baseline only. Assessments of troponin I and NT-pro-BNP levels will be made at each study visit.

Blood samples for pharmacokinetic assessments (Fx-1006A concentrations as well as calculated steady-state parameters) and pharmacodynamic assessments (TTR stabilization) will be collected at Week 6 and Months 6 and 12.

Safety and tolerability will be assessed throughout the study. Vital signs, 12-lead ECG, blood and urine samples for clinical laboratory tests (serum chemistry, hematology, coagulation panel, urinalysis, and urine pregnancy testing), adverse events, and concomitant medications will be assessed at each study visit. Eye examinations (including fundal photography) will be conducted at Months 6 and 12. Abbreviated physical examinations will be conducted at Week 6, and Months 3 and 6, and a complete physical examination will be conducted at Month 12.

All patients will be contacted by telephone 30 days (± 1 week) after the last dose of study medication for assessment of adverse events and concomitant medications.

Patients who complete the Month 12 visit of this open-label study may be allowed to continue receiving Fx-1006A under a compassionate use program.

Patients who discontinue from the study at any time after enrollment (i.e., early termination) will have final safety assessments performed at the time of discontinuation. Any patient discontinuing after the Month 6 visit will have all safety and clinical outcomes assessments scheduled for the Month 12 visit performed.

Conditions

Familial Amyloid Polyneuropathy; ATTR-PN

Keywords

FAP; Familial Amyloid Polyneuropathy; ATTR-PN; transthyretin; TTR; amyloid; polyneuropathy; familial; hereditary; amyloidosis; FoldRx

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Fx-1006A

Group Type: EXPERIMENTAL

Fx-1006A

Intervention Type: DRUG

Fx-1006A 20mg soft gelatin capsule administered orally once daily (at the same time each day) for 12 months.

Interventions

Fx-1006A

Fx-1006A 20mg soft gelatin capsule administered orally once daily (at the same time each day) for 12 months.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Male and non-pregnant female patients meeting all of the following criteria are eligible for enrollment in this study:

• Patient has completed the Month 18 visit of Study Fx-005.
• If female, patient is post-menopausal, surgically sterilized, or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide) throughout the study. (A condom alone is not considered 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, acceptable 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.
• Patient agrees not to participate in another investigational drug or device study while participating in this open-label extension study.

Exclusion Criteria

• Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), defined as greater than 3-4 times/month (ibuprofen and nimesulide will be permitted).
• If female, patient is pregnant or breast feeding.
• Patient has liver function test abnormalities: alanine transaminases (ALT) and/or aspartate transaminases (AST) >2 times upper limit of normal (ULN) that in the medical judgment of the investigator are due to reduced liver function or active liver disease.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeff Packman

Role: STUDY_DIRECTOR

FoldRx Pharmaceuticals, Inc.

Locations

FLENI Departamento de Hepatología y Transplante de Organos

Buenos Aires, , Argentina

FLENI-Hepatology and Organ Transplant Dept.

Ciudad de Buenos Aires, , Argentina

Hospital Universitario Clementino Fraga Filho

Rio de Janeiro, , Brazil

Service de Neurologie, CHU Henri Mondor

Paris, , France

Universitatsklinikum Munster, Transplant Hepatology

Münster, , Germany

Serviço de Neurologia-Hospital de Santa Maria

Lisbon, , Portugal

Servicio de Neurologica Piso 7, Hospital de Santa Maria

Lisbon, , Portugal

Unidade Clinica de Paramiloidose-Hospital Santo Antonio

Porto, , Portugal

Unidade Clinica de Paramiloidose, Hospital Geral de Santo Antonio, Largo Prof Abdel Salazar

Porto, , Portugal

Umea University Hospital

Umeå, , Sweden

FAP-Teamet Familjar Amyloids, Norrlands universitetssjukhus

Umeå, , Sweden

Countries

Argentina; Brazil; France; Germany; Portugal; Sweden

References

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)

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)

Coelho T, Maia LF, da Silva AM, Cruz MW, Plante-Bordeneuve V, Suhr OB, Conceicao I, Schmidt HH, Trigo P, Kelly JW, Labaudiniere R, Chan J, Packman J, Grogan DR. Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy. J Neurol. 2013 Nov;260(11):2802-14. doi: 10.1007/s00415-013-7051-7. Epub 2013 Aug 22.

Reference Type: DERIVED

PMID: 23974642 (View on PubMed)

Other Identifiers

B3461021

Identifier Type: -

Identifier Source: secondary_id

FX-006

Identifier Type: -

Identifier Source: org_study_id