Trial record 4 of 28 for:    "transthyretin amyloidosis"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2015 by Isis Pharmaceuticals
Information provided by (Responsible Party):
Isis Pharmaceuticals Identifier:
First received: November 27, 2012
Last updated: August 7, 2015
Last verified: August 2015
The purpose of this study is to evaluate the efficacy and safety of ISIS-TTR Rx given for 65 weeks in patients with Familial Amyloid Polyneuropathy

Condition Intervention Phase
Familial Amyloid Polyneuropathy
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:

Further study details as provided by Isis Pharmaceuticals:

Primary Outcome Measures:
  • Efficacy of ISIS-TTR Rx as measured by change from baseline in the modified Neuropathy Impairment Score +7 [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
  • Efficacy of ISIS-TTR Rx as measured by change from baseline in the Norfolk Quality of Life Diabetic Neuropathy questionnaire [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Efficacy of ISIS-TTR Rx based on the change from baseline in the following measures: [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]
    • Modified Body Mass Index and Body Mass Index
    • Individual components of the mNIS+7
    • NIS+7

  • Pharmacodynamic effect of ISIS-TTR Rx based on the change from baseline in transthyretin and retinol binding protein 4 [ Time Frame: 65 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 195
Study Start Date: December 2012
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: ISIS-TTR Rx Drug: ISIS-TTR Rx
300 mg ISIS-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.

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.

ISIS-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 ISIS-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 ISIS-TTR Rx or placebo for 65 weeks.


Ages Eligible for Study:   18 Years to 82 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01737398

Contact: Isis Pharmaceuticals, Inc. 800-679-4747

  Show 25 Study Locations
Sponsors and Collaborators
Isis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: Isis Pharmaceuticals Identifier: NCT01737398     History of Changes
Other Study ID Numbers: ISIS 420915-CS2
Study First Received: November 27, 2012
Last Updated: August 7, 2015
Health Authority: United States: Food and Drug Administration
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Ministry of Health
Portugal: National Pharmacy and Medicines Institute
Germany: Ministry of Health
Italy: Ministry of Health
Argentina: Ministry of Health
Bulgaria: Ministry of Health
Spain: Ministry of Health
Brazil: Ministry of Health

Keywords provided by Isis Pharmaceuticals:
Familial Amyloid Polyneuropathy

Additional relevant MeSH terms:
Amyloid Neuropathies
Amyloid Neuropathies, Familial
Amyloidosis, Familial
Genetic Diseases, Inborn
Heredodegenerative Disorders, Nervous System
Metabolic Diseases
Metabolism, Inborn Errors
Nervous System Diseases
Neurodegenerative Diseases
Neuromuscular Diseases
Peripheral Nervous System Diseases
Proteostasis Deficiencies processed this record on November 27, 2015