ClinicalTrials.gov
ClinicalTrials.gov Menu

Efficacy and Safety of Inotersen in Familial Amyloid Polyneuropathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01737398
Recruitment Status : Completed
First Posted : November 29, 2012
Last Update Posted : June 19, 2018
Sponsor:
Information provided by (Responsible Party):
Ionis Pharmaceuticals, Inc.

Brief Summary:
The purpose of this study was to evaluate the efficacy and safety of inotersen given for 65 weeks in participants with Familial Amyloid Polyneuropathy (FAP).

Condition or disease Intervention/treatment Phase
FAP Familial Amyloid Polyneuropathy TTR Transthyretin Amyloidosis Drug: Inotersen Drug: Placebo Phase 2 Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Detailed Description:

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.

Inotersen (also known as ISIS 420915) is an antisense drug that was designed to decrease the amount of mutant and normal TTR made by the liver. It was predicted that decreasing the amount of TTR protein would result in a decrease in the formation of TTR deposits, and thus slow or stop disease progression.

The purpose of this study was to determine if inotersen could slow or stop the nerve damage caused by TTR deposits. This study enrolled late Stage 1 and early Stage 2 FAP participants. Participants received either inotersen 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 (NEURO-TTR Study)
Actual Study Start Date : March 15, 2013
Actual Primary Completion Date : March 3, 2017
Actual Study Completion Date : November 7, 2017


Arm Intervention/treatment
Active Comparator: Inotersen
300 mg inotersen administered subcutaneously (SC) 3 times on alternate days in the first week and then once-weekly for 64 weeks
Drug: Inotersen
Other Names:
  • TEGSEDI
  • IONIS-TTR Rx
  • ISIS 420915

Active Comparator: Placebo
Placebo administered SC 3 times on alternate days in the first week and then once-weekly for 64 weeks
Drug: Placebo



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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Stage 1 and Stage 2 FAP participants 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 used appropriate contraception and were non-pregnant and non-lactating. Males engaged in relations of child-bearing potential used 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 (for example, autoimmune disease)
  • If previously treated with Vyndaqel®, had discontinued treatment for 2 weeks prior to Study Day 1. If previously treated with Diflunisal, had 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 year 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
  • Had any other conditions in the opinion of the investigator which interfered with the participant 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:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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: June 19, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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