To obtain additional, long term, safety data for tafamidis in subjects with transthyretin amyloid cardiomyopathy (ATTR CM). To provide investigational product, tafamidis, to ATTR CM subjects who complete 30 months of blinded treatment on protocol…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Safety as measured by:
* All cause mortality.
* Incidence of treatment emergent adverse events.
Secondary outcome
Other Endpoints
* Cardiovascular related mortality.
* Frequency of all cause hospitalization.
* Frequency of cardiovascular related hospitalization (including heart failure,
arrhythmia, myocardial infarction, stroke and other cardiovascular related
events).
* Change from baseline at each visit in Kansas City Cardiomyopathy
Questionnaire Overall Score and domain scores (Physical limitation, Symptom
stability, Symptoms, Self efficacy, Social limitation, and Quality of life) and
domain summary scores (Functional summary and Clinical summary).
* New York Heart Association classification at each visit.
* Change from baseline in Body Mass Index/modified Body Mass Index at each
visit.
* Assessment of physical examinations, use of concomitant medications,
electrocardiograms (ECGs), clinical laboratory testing, vital signs at each
visit.
Background summary
Pfizer is developing tafamidis, an oral small molecule, for the treatment of
transthyretin amyloid diseases. Transthyretin cardiomyopathy (ATTR CM) occurs
when transthyretin (ATTR) amyloid fibrils infiltrate the myocardium, leading to
deposits of extracellular amyloid. Deposition of transthyretin fibrils occurs
between the myocardial cells and produces a thickening and stiffening of the
myocardial tissue. This infiltration of the myocardium results in diastolic
dysfunction progressing to restrictive cardiomyopathy, congestive heart
failure, and ultimately death.
Tafamidis is a novel specific stabilizer of both wild type and amyloidogenic
variants of ATTR. Tafamidis binds to ATTR at the thyroxine binding sites and
inhibits ATTR tetramer dissociation, the rate limiting step in the
amyloidogenic process. It is hypothesized that tafamidis would stop or slow the
progression of ATTR CM and therefore represents a disease modifying therapy.
Study objective
To obtain additional, long term, safety data for tafamidis in subjects with
transthyretin amyloid cardiomyopathy (ATTR CM).
To provide investigational product, tafamidis, to ATTR CM subjects who complete
30 months of blinded treatment on protocol B3461028.
Study design
This is a Phase 3, open-label long-term extension safety study designed to
obtain additional safety data for tafamidis meglumine 20 mg and 80 mg
tafamidis (or tafamidis 61 mg where available), and to continue to provide
enrolled subjects with tafamidis for up to 60 months, or until subject has
access to tafamidis for ATTR-CM via prescription, whichever occurs first. The
study will also end before 60 months if the sponsor discontinues the
study. Subjects withdrawn from the study due to commercial access to
prescription tafamidis in their respective countries will be considered study
completers. The decision to withdraw subjects for transition to commercial
tafamidis will be made by the sponsor
Patients who received 20 mg or 80 mg (or potentially 40 mg) tafamidis in Study
B3461028, will continue to receive tafamidis at the dose of 61 mg.
New patients will receive 61 mg Tafemidis.
Intervention
Tafamidis is available in 61 mg soft gel capsules, and subjects will take 1
capsules per day
Study burden and risks
Very Common (reported in at least 10% of patients)
o Fall
o Heart failure
o Dyspnea
o Atrial fibrillation
o Peripheral edema
o Fatigue
o Dizziness
o Constipation
From a study in which 65 patients with ATTR-PN received tafamidis 20 mg daily
for up to 18 months, the following risks are considered associated with
tafamidis use in ATTR-PN patients.
Very Common (reported in at least 10% of patients)
o Diarrhea
o Urinary tract infection
o Upper abdominal pain.
o Vaginal infections in women
Risks from Study Procedures:
* Biopsy: The risks of a biopsy can include bleeding, pain, and infection.
* Blood draws: A blood draw may cause faintness, inflammation of the vein,
pain, bruising, or bleeding at the site of puncture. There is also a slight
chance of infection.
* ECG: The risks from an ECG can include skin irritation and a rash from the
gel that is used or from wearing or removing the patches that are used to
conduct the measurements.
* Questionnaires: A questionnaire may contain questions that are sensitive in
nature.
* Scintigraphy: The amount of radiation received as part of this study is
small. There is no significant risk from this total amount of radiation.
* Testing of DNA and/or RNA: The genetic analysis is for research purposes
only, and is not a medical test. The Sponsor and researchers will put measures
in place to minimize the possibility for the results from this research being
linked to the subject, but there is always the remote possibility that
information from participation in the research may be disclosed.
Possible benefit:
Previous results demonstrated that tafamidis reduced all-cause mortality and
cardiovascular (CV)-related hospitalisation in addition to better function and
quality of life compared with placebo.
East 42nd Street 235
New York NY 10017
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East 42nd Street 235
New York NY 10017
US
Listed location countries
Age
Inclusion criteria
1. Male and female subjects with TTR amyloid cardiomyopathy who have completed
30 months of study treatment on Protocol B3461028.
2. Evidence of a personally signed and dated informed consent document
indicating that the subject has been informed of all pertinent aspects of the
study.
3. Subjects who are willing and able to comply with scheduled visits, treatment
plan, laboratory tests, and other study procedures.
4. Male subjects able to father children and female subjects of childbearing
potential and at risk for pregnancy must agree to use 2 highly effective
methods of contraception hroughout the study and for at least 28 days after the
last dose of assigned treatment.
Female subjects who are not of childbearing potential (ie, meet at least 1 of
the following criteria):
* Have undergone a documented hysterectomy and/or bilateral oophorectomy;
* Have medically confirmed ovarian failure; or
* Achieved postmenopausal status, defined as follows: cessation of regular
menses for at least 12 consecutive months with no alternative pathological or
physiological cause; status may be confirmed by having a serum
folliclestimulating hormone (FSH) level confirming the post-menopausal state.
All other female subjects (including females with tubal ligations) will be
considered o be of childbearing potential.
Aanvullend voor cohort B:
5. Documentatie van de genetische tests voor transthyretineamyloïdose
6. Documentatie van diagnose en gebruikte criteria of congestief hartfalen en
de aanwezigheid van
amyloïde afzettingen in biopsieweefsel, b.v. vetaspiratie, speekselklier,
nervus medianus
bindweefselschede of cardiaal
7.Documentatie dat primaire (lichte keten) amyloïdose ziekte is geëvalueerd en
uitgesloten
8. Bewijs van NYHA-classificatie I, II, III of IV
Exclusion criteria
1. Chronic use of diflunisal, TTR stabilizer, tauroursodeoxycholate,
doxycycline, digitalis, patisaran, calcium channel blockers, investigational
drug(s) or other experimental interventions, other than tafamidis,
independently or as part of a study within 30 months prior to enrollment, or
inotersen within 6 months prior to enrolment
2. Use of certain non-steroidal anti-inflammatory drugs (NSAIDs)
3. Liver and/or heart transplant, or implanted cardiac mechanical assist device.
4. Pregnant females (or planning to become pregnant during the study interval);
breastfeeding females; male subjects with partners currently pregnant.
5. Require initiation of treatment with calcium channel blockers.
6. Urinary retention requiring chronic self-catheterization.
7. Breach of compliance with treatment/significant protocol violations during
conduct of B3461028 for which the subject was accountable.
8. Subjects who are investigational site staff members directly involved in the
conduct of the study and their family members, site staff members otherwise
supervised by the investigator, or subjects who are Pfizer employees directly
involved in the conduct of he study.
9. Other severe acute or chronic medical or psychiatric condition or laboratory
bnormality that may increase the risk associated with study participation or
investigational product administration, or that may interfere with the
interpretation of study results and, in the judgment of the investigator, would
make the subject an appropriate for entry into this study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2016-000868-42-NL |
| CCMO | NL58803.028.17 |