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WithdrawnNCT02627820Updated Aug 10, 2016

The Effect of an Antisense Oligonucleotide to Lower Transthyretin (TTR) Levels on the Progression of -Wild-type TTR Involving the Heart

A Phase 2 interventional study of Isis 420915/GSK 299872 in Amyloidosis, sponsored by Brigham and Women's Hospital. Withdrawn. Open to participants aged 50 Years to 90 Years. Per ClinicalTrials.gov, last updated 2016-08-10.

Sponsored by Brigham and Women's Hospital · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
0
Allocation
Not applicable
Ages
50 Years to 90 Years
Sex
All
01

Study summary

ATTRwt (also known as senile systemic, or senile cardiac amyloidosis) is a progressive heart disease, causing congestive heart failure. It is caused by amyloid protein deposits in the heart, that are derived from a normal protein, TTR, made in the liver. The aim of the study is to determine whether lowering the blood levels of TTR, by a weekly injection of a compound designed specifically to do this, will slow the progression of the disease when treated patients are compared to previously-followed patients who were not receiving this drug. The study also aims to determine how well this drug is tolerated and the existence and severity of any drug side-effects.

02

Conditions studied

  • Amyloidosis

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Keywords

  • Senile
  • ATTRwt
  • wild-type transthyretin amyloidosis
03

In context

Amyloidosis

491 studies on the registry are indexed under Amyloidosis; 135 are open to participants now.

Browse Amyloidosis studies →

Lead sponsor

Brigham and Women's Hospital is the lead sponsor of 1,236 studies on the registry; 224 are open to participants now.

Of its 116 completed or terminated interventional studies of FDA-regulated products, 64 (55%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
50 Years to 90 Years
Sexes eligible
All
Accepts healthy volunteers
No

All patients with documented SSA will be considered for inclusion. SSA is defined as an echocardiographic appearance of left ventricular wall thickness of 13 mm or more, in the absence of uncontrolled hypertension, and with a positive biopsy for amyloid, which also stains positive for TTR by immunochemistry or mass spectrometry. For the definition of SSA, genetic testing should be negative for a mutation. Identification of amyloid type is standard of care for all patients seen at the Cardiac Amyloidosis Program and the presence of a clinically -obtained positive biopsy will be a requirement for study inclusion. The positive biopsy can be from any organ, providing that the echocardiographic appearance is typical of amyloidosis.

Inclusion criteria

Inclusion Criteria:

  1. Patients should, in the opinion of the Investigator, be in a stable state in terms of NYHA class. Class I-III patients will be recruited.
  2. Age 50-90 years
  3. Male or non-pregnant, non-lactating females. If a woman is premenopausal, or a male partners with a premenopausal woman, she/he must be willing to use the following methods of contraception: condoms, oral/hormonal contraception, Intrauterine Device, diaphragm, or abstinence
  4. Written informed consent to be obtained prior to study treatment
  5. Histochemical diagnosis of amyloidosis as based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens
  6. Molecular definition of the absence of a TTR mutation or immunohistochemical staining of amyloid fibrils with anti TTR antibody and negative genetic testing for a TTR mutation.
  7. Willingness to return to the treating center for follow-up.
  8. Willingness and ability to self-administer, or to have spouse administer weekly subcutaneous injections of study drug.

Exclusion criteria

Exclusion Criteria:

  1. Patients who, in the opinion of the Investigator, require further adjustment of diuretics at the time of screening to achieve optimal treatment of heart failure. Once stable for 2 weeks, patients in Class I-III will become eligible for inclusion.
  2. Patients with NYHA class 4 congestive heart failure.
  3. Concomitant non-amyloid heart disease that might, in the opinion of the investigator, cause changes in strain imaging on serial follow-up (e.g. aortic stenosis of greater than mild severity, unstable coronary artery disease).
  4. Prior liver transplantation or liver transplantation anticipated in less than 6 months;
  5. ALT and/or AST ³ 2 x ULN and/or Alkaline phosphatase ³ 2 x UNL;
  6. Estimated glomerular filtration rate (EGFR) \< 50 ml/min;
  7. Any other lab values that in the opinion of the investigator might place the subject at unacceptable risk for participation in the study;
  8. History of poor compliance with medications or medical treatment, based on a review of medical records.
  9. History of hypersensitivity to any of the ingredients of the study therapy;
  10. Use of any investigational drug for amyloidosis within 4 weeks prior to study entry or during the study.
  11. Current use of tafamidis, diflunisal, doxycycline or TUDCA for therapy of amyloidosis.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
0 participants (actual)

Study arms

  • Experimental
    Experimental Drug

    Isis 420915/GSK 299872, an antisense oligonucleotide. Administered subcutaneously three times per week for the first week, and then weekly for 18 months. Each dose shall contain 300 mg of active drug.

    Drug: Isis 420915/GSK 299872

Interventions

  • DrugIsis 420915/GSK 299872

    Open label study in comparison to historic control.

    Also known as: Antisense oligonucleotide

06

What researchers measure

Primary outcomes

  1. Systolic strain imaging by echocardiographic speckle tracking

    The primary echocardiographic parameter to be measured will be longitudinal left ventricular (LV) strain (units = % LV longitudinal shortening) as compared to baseline.

    Time frame: Month 12

Secondary outcomes

  1. Systolic strain evaluation by echocardiography

    The primary echocardiographic parameter measured will be longitudinal left ventricular (LV) strain (units = %).

    Time frame: Secondary analysis will occur at 18 months

  2. Echocardiographic determination of Mean thickness of LV septum and posterior wall (units = mm)

    Time frame: 12 months

  3. Echocardiographic determination of Mean thickness of LV septum and posterior wall (units = mm)

    Time frame: 18 months

  4. Echocardiographic determination of LV ejection fraction (units = %)

    Time frame: 12 months

  5. Echocardiographic determination of LV ejection fraction (units = %)

    Time frame: 18 months

  6. LV mass measurement by Cardiac MRI (cMRI) (units = grams)

    Time frame: 18 months

  7. LV cellular component as determined by cMRI (units = % of total LV mass)

    Time frame: 12 months

  8. LV cellular component as determined by cMRI (units = % of total LV mass)

    Time frame: 18 months

  9. LV extracellular component as determined by cMRI (units = % of total LV mass)

    Time frame: 12 months

  10. LV extracellular component as determined by cMRI (units = % of total LV mass)

    Time frame: 18 months

  11. Extent of cMRI late gadolinium enhancement of the LV (unites = % of area)

    Time frame: 12 months

  12. Extent of cMRI late gadolinium enhancement of the LV (unites = % of area)

    Time frame: 18 months

  13. LV mass measurement by Cardiac MRI (cMRI) (units = grams)

    Time frame: Month 12

07

Study locations

No study locations are listed for this record.

08

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 10, 2016, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT02627820
Lead sponsor
Brigham and Women's Hospital
Collaborators
GlaxoSmithKline, Ionis Pharmaceuticals, Inc.
Responsible party
Rodney H. Falk, MD (Director, Brigham and Women's Cardiac Amyloidosis Program, Brigham and Women's Hospital) — Principal investigator
First posted
Dec 11, 2015
Start date
Jan 2016
Primary completion
Dec 2018 (estimated)
Completion
Dec 2018 (estimated)
Last update
Aug 10, 2016

Study contacts

Rodney H Falk, MD
principal investigator · Brigham and Women's Hospital
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is withdrawn, as verified in Jan 2016. You cannot join it, but the record below documents what was studied.

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