Open-Label Extension Assessing Long Term Safety and Efficacy of IONIS-TTR Rx in Familial Amyloid Polyneuropathy (FAP)

Sponsor

Ionis Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT02175004

Collaborator

(none)

135

Enrollment

Locations

Arm

79.2

Actual Duration (Months)

6.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study evaluates the safety and tolerability of extended dosing with IONIS-TTR Rx in patients with Familial Amyloid Polyneuropathy.

Condition or Disease	Intervention/Treatment	Phase
FAP Familial Amyloid Polyneuropathy TTR Transthyretin Amyloidosis	Drug: IONIS-TTR Rx	Phase 3

Detailed Description

Familial Amyloid Polyneuropathy (FAP) is a rare, hereditary disease caused by mutations in the transthyretin (TTR) protein. TTR is made by the liver and secreted into the blood. TTR mutations cause it to misfold and deposit in multiple organs causing FAP.

IONIS-TTR Rx is an antisense drug that is designed to decrease the amount of mutant and normal TTR made by the liver. It is predicted that decreasing the amount of TTR protein will result in a decrease in the formation of TTR deposits, and thus slow or stop disease progression.

This study evaluates the safety and tolerability of extended dosing with IONIS-TTR Rx in patients with Familial Amyloid Polyneuropathy.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

135 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-Label Extension Study to Assess the Long-Term Safety and Efficacy of ISIS 420915 in Patients With Familial Amyloid Polyneuropathy (FAP)

Actual Study Start Date :

Jun 1, 2014

Actual Primary Completion Date :

Jan 7, 2021

Actual Study Completion Date :

Jan 7, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IONIS-TTR Rx	Drug: IONIS-TTR Rx 300 mg IONIS-TTR Rx administered once weekly

Arm

Intervention/Treatment

Experimental: IONIS-TTR Rx

Drug: IONIS-TTR Rx

300 mg IONIS-TTR Rx administered once weekly

Outcome Measures

Primary Outcome Measures

Types of adverse events that occur during treatment [Week 52 of Year 5]
Change from baseline in blood pressure (systolic and diastolic), heart rate, and body weight [Week 52 of Year 5]
Change from baseline in results of routine laboratory test panel (routine serum chemistry, hematology, and urinalysis) [Week 52 of Year 5]
Change from baseline in QTcF determined from electrocardiogram measurements [Week 52 of Year 5]
Change from baseline in number of concomitant medications used [Week 52 of Year 5]
Change from baseline in visual acuity measured during ophthalmic exam [Week 52 of Year 5]
Change from baseline in light detection ability measured by electroretinography [Week 52 of Year 5]

Secondary Outcome Measures

Change from baseline in the modified Neuropathy Impairment Score +7 [78 and 156 Weeks]
Change from baseline in the Neuropathy Impairment Score [Week 52 of Years 4 and 5]
Change from baseline in the Norfolk Quality of Life Diabetic Neuropathy Questionnaire [Week 78, 156 and Week 52 of Years 4 and 5]
Change from baseline in the Modified body mass index (mBMI) and body mass index (BMI) [78 and 156 Weeks]
Change from baseline in the Polyneuropathy disability score (PND) [Week 78, 156 and Week 52 of Years 4 and 5]
Change in baseline in Transthyretin (TTR) and Retinol Binding Protein 4 (RBP4) [Week 78, 156 and Week 52 of Years 4 and 5]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Satisfactory completion of dosing & efficacy assessments in ISIS 420915-CS2

Exclusion Criteria:

Any new condition or worsening of existing condition that could make the patient unsuitable for participation, or interfere with the patient participating in and/or completing the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California, Irvine	Orange	California	United States	92868
2	Indiana University School of Medicine	Indianapolis	Indiana	United States	46202
3	Johns Hopkins University Bayview Medical Center	Baltimore	Maryland	United States	21205
4	Boston University School of Medicine - Amyloid Treatment & Research Program	Boston	Massachusetts	United States	02118
5	Mayo Clinic	Rochester	Minnesota	United States	55905
6	Mount Sinai Medical Center	New York	New York	United States	10029
7	Columbia University Medical Center - The Neurological Institute	New York	New York	United States	10032
8	Oregon Health & Science University	Portland	Oregon	United States	97239
9	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania	United States	19104
10	FLENI	Buenos Aires		Argentina
11	Federal University of Rio de Janeiro - University Hospital	Rio de Janeiro		Brazil	CEP 21941913
12	AACD	Sao Paulo		Brazil
13	CHU Henri Mondor - Department of Neurology	Creteil		France	94000
14	CHU Bicetre Aphp French Referral Center for FAP/Cornamyl Network	Le Kremlin Bicetre		France	94275
15	UKM; Universitätsklinikum Münster, Klinik für Transplantationsmedizin	Munster		Germany	48149
16	Universita Degli Studi Di Messina - Azienda Ospedaliera Universitaria Policlinico "Gaetano Martino"	Messina	Sicily	Italy	98124
17	Centro per lo Studio e la Cura delle Amiloidosi Sistemiche - Fondazione IRCCS Policlinico San Matteo	Pavia		Italy	27100
18	CHLN - Hospital de Santa Maria	Lisbon		Portugal	1649-035
19	CHP-HGSA, Unidade Clinica de Paramiloidose	Porto		Portugal	4099-001
20	Hospital Universitari Vall D' Hebron	Barcelona		Spain	08035
21	Hospital Clinic	Barcelona		Spain	08036
22	University College London - National Amyloidosis Centre	London		United Kingdom	NW3 2PF