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Efficacy and Safety of IONIS-TTR Rx in Familial Amyloid Polyneuropathy

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ClinicalTrials.gov Identifier: NCT01737398
Recruitment Status : Completed
First Posted : November 29, 2012
Last Update Posted : November 8, 2017
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of IONIS-TTR Rx given for 65 weeks in patients with Familial Amyloid Polyneuropathy

Condition or disease Intervention/treatment Phase
FAP Familial Amyloid Polyneuropathy TTR Transthyretin Amyloidosis Drug: IONIS-TTR Rx Drug: Placebo 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.

The purpose of this study is to determine if IONIS-TTR Rx can slow or stop the nerve damage caused by TTR deposits. This study will enroll late Stage 1 and early Stage 2 FAP patients. Patients will receive either IONIS-TTR Rx or placebo for 65 weeks.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 172 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2/3 Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of ISIS 420915 in Patients With Familial Amyloid Polyneuropathy
Actual Study Start Date : December 2012
Primary Completion Date : March 2017
Study Completion Date : October 2017


Arm Intervention/treatment
Active Comparator: IONIS-TTR Rx Drug: IONIS-TTR Rx
300 mg IONIS-TTR Rx administered subcutaneously 3 times on alternate days in the first week and then once-weekly for 64 weeks.
Active Comparator: Placebo Drug: Placebo
Placebo administered subcutaneously 3 times on alternate days in the first week and then once-weekly for 64 weeks.



Primary Outcome Measures :
  1. Efficacy of IONIS-TTR Rx as measured by change from baseline in the modified Neuropathy Impairment Score +7 [ Time Frame: 65 weeks ]
  2. Efficacy of IONIS-TTR Rx as measured by change from baseline in the Norfolk Quality of Life Diabetic Neuropathy questionnaire [ Time Frame: 65 weeks ]

Secondary Outcome Measures :
  1. Efficacy of IONIS-TTR Rx based on the change from baseline in the following measures: [ Time Frame: 65 weeks ]
    • Modified Body Mass Index and Body Mass Index
    • Individual components of the mNIS+7
    • NIS+7

  2. Pharmacodynamic effect of IONIS-TTR Rx based on the change from baseline in transthyretin and retinol binding protein 4 [ Time Frame: 65 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 82 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Stage 1 and Stage 2 FAP patients with the following:

    1. NIS score within protocol criteria
    2. Documented transthyretin variant by genotyping
    3. Documented amyloid deposit by biopsy
  • Females of child-bearing potential must use appropriate contraception and must be non-pregnant and non-lactating. Males engaged in relations of child-bearing potential must use appropriate contraception

Exclusion Criteria:

  • Low Retinol level at screen
  • Karnofsky performance status ≤50
  • Poor Renal function
  • Known type 1 or type 2 diabetes mellitus
  • Other causes of sensorimotor or autonomic neuropathy (e.g., autoimmune disease)
  • If previously treated with Vyndaqel®, must have discontinued treatment for 2 weeks prior to Study Day 1. If previously treated with Diflunisal, must have discontinued treatment for 3 days prior to Study Day 1
  • Previous treatment with any oligonucleotide or siRNA within 12 months of screening
  • Prior liver transplant or anticipated liver transplant within 1 yr of screening
  • New York Heart Association (NYHA) functional classification of ≥3
  • Acute Coronary Syndrome or major surgery within 3 months of screening
  • Known Primary or Leptomeningeal Amyloidosis
  • Anticipated survival less than 2 years
  • Have any other conditions in the opinion of the investigator which could interfere with the patient participating in or completing the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01737398


  Show 24 Study Locations
Sponsors and Collaborators
Ionis Pharmaceuticals, Inc.

Additional Information:
Responsible Party: Ionis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01737398     History of Changes
Other Study ID Numbers: ISIS 420915-CS2
First Posted: November 29, 2012    Key Record Dates
Last Update Posted: November 8, 2017
Last Verified: November 2017

Keywords provided by Ionis Pharmaceuticals, Inc.:
FAP
Familial Amyloid Polyneuropathy
TTR
Transthyretin
Amyloidosis

Additional relevant MeSH terms:
Amyloidosis
Polyneuropathies
Amyloid Neuropathies
Amyloid Neuropathies, Familial
Proteostasis Deficiencies
Metabolic Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Genetic Diseases, Inborn
Amyloidosis, Familial
Metabolism, Inborn Errors