AmyloidosisPhase 2NCT02627820
The Effect of an Antisense Oligonucleotide to Lower Transthyretin (TTR) Levels on the Progression of -Wild-type TTR Involving the Heart
A Phase 2 study testing Isis 420915/GSK 299872 in people with Amyloidosis, run by Brigham and Women's Hospital.
Trial 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. Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Amyloidosis
- What is being tested?
- Isis 420915/GSK 299872
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2016to Dec 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Age 50-90 years
- 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
- Written informed consent to be obtained prior to study treatment
- Histochemical diagnosis of amyloidosis as based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens
- 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.
- Willingness to return to the treating center for follow-up.
- Willingness and ability to self-administer, or to have spouse administer weekly subcutaneous injections of study drug.
Who cannot join
- 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.
- Patients with NYHA class 4 congestive heart failure.
- 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).
- Prior liver transplantation or liver transplantation anticipated in less than 6 months;
- ALT and/or AST ³ 2 x ULN and/or Alkaline phosphatase ³ 2 x UNL;
- Estimated glomerular filtration rate (EGFR) < 50 ml/min;
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- Any other lab values that in the opinion of the investigator might place the subject at unacceptable risk for participation in the study;
- History of poor compliance with medications or medical treatment, based on a review of medical records.
- History of hypersensitivity to any of the ingredients of the study therapy;
- Use of any investigational drug for amyloidosis within 4 weeks prior to study entry or during the study.
- Current use of tafamidis, diflunisal, doxycycline or TUDCA for therapy of amyloidosis.
About this study
Official title: An 18 Month Open Label Study Of The Tolerability And Efficacy Of An Antisense Oligonucleotide In Patients With Wild-Type Transthyretin Amyloid Cardiomyopathy (Senile Systemic Amyloidosis)
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.
- Conditions
- Amyloidosis
- Being tested
- Isis 420915/GSK 299872
- Keywords
- Senile, ATTRwt, wild-type transthyretin amyloidosis
- Medical subject headings
- Amyloidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Isis 420915/GSK 299872Drug
Also called Antisense oligonucleotide
Open label study in comparison to historic control.
| Study group | Role | What they receive |
|---|---|---|
| Experimental Drug | Experimental | 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. Receives: Drug: Isis 420915/GSK 299872 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Month 12
Secondary outcomes (13)
Systolic strain evaluation by echocardiography
The primary echocardiographic parameter measured will be longitudinal left ventricular (LV) strain (units = %).
Measured: Secondary analysis will occur at 18 months
Echocardiographic determination of Mean thickness of LV septum and posterior wall (units = mm)
Measured: 12 months
Echocardiographic determination of Mean thickness of LV septum and posterior wall (units = mm)
Measured: 18 months
Echocardiographic determination of LV ejection fraction (units = %)
Measured: 12 months
Echocardiographic determination of LV ejection fraction (units = %)
Measured: 18 months
LV mass measurement by Cardiac MRI (cMRI) (units = grams)
Measured: 18 months
LV cellular component as determined by cMRI (units = % of total LV mass)
Measured: 12 months
LV cellular component as determined by cMRI (units = % of total LV mass)
Measured: 18 months
LV extracellular component as determined by cMRI (units = % of total LV mass)
Measured: 12 months
LV extracellular component as determined by cMRI (units = % of total LV mass)
Measured: 18 months
Extent of cMRI late gadolinium enhancement of the LV (unites = % of area)
Measured: 12 months
Extent of cMRI late gadolinium enhancement of the LV (unites = % of area)
Measured: 18 months
LV mass measurement by Cardiac MRI (cMRI) (units = grams)
Measured: Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2015 (estimated)
- Study startJan 2016
- Primary completionDec 2018 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AmyloidosisStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline, Ionis Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Rodney H. Falk, MD, Brigham and Women's Hospital
- Investigators
- Rodney H Falk, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02627820
- Sponsor's protocol ID
- 2015-P001574
- Status last verified
- Jan 2016
- First submitted
- 19 Nov 2015
- Last updated
- 10 Aug 2016
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An 18 Month Open Label Study Of The Tolerability And Efficacy Of An Antisense Oligonucleotide In Patients With Wild-Type Transthyretin Amyloid Cardiomyopathy (Senile Systemic Amyloidosis)
- ClinicalTrials.gov ID
- NCT02627820
- Acronym / sponsor ID
- 2015-P001574
- Conditions
- Amyloidosis
- Keywords
- Senile, ATTRwt, wild-type transthyretin amyloidosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- GlaxoSmithKline, Ionis Pharmaceuticals, Inc.
- Study start
- Jan 2016
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 11 Dec 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental Drug | Experimental | Drug: Isis 420915/GSK 299872Isis 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. |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
- Age 50-90 years
- 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
- Written informed consent to be obtained prior to study treatment
- Histochemical diagnosis of amyloidosis as based on detection by polarizing microscopy of green birefringent material in Congo red-stained tissue specimens
Key exclusion criteria (11 listed)
- 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.
- Patients with NYHA class 4 congestive heart failure.
- 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).
- Prior liver transplantation or liver transplantation anticipated in less than 6 months;
- ALT and/or AST ³ 2 x ULN and/or Alkaline phosphatase ³ 2 x UNL;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Isis 420915/GSK 299872Also: Antisense oligonucleotideOpen label study in comparison to historic control. | Drug | Experimental Drug |
Primary outcome
Systolic strain imaging by echocardiographic speckle tracking
Time frame: Month 12
The primary echocardiographic parameter to be measured will be longitudinal left ventricular (LV) strain (units = % LV longitudinal shortening) as compared to baseline.
13 secondary outcomes
Systolic strain evaluation by echocardiography
Time frame: Secondary analysis will occur at 18 months
Echocardiographic determination of Mean thickness of LV septum and posterior wall (units = mm)
Time frame: 12 months
Echocardiographic determination of Mean thickness of LV septum and posterior wall (units = mm)
Time frame: 18 months
Echocardiographic determination of LV ejection fraction (units = %)
Time frame: 12 months
Echocardiographic determination of LV ejection fraction (units = %)
Time frame: 18 months
LV mass measurement by Cardiac MRI (cMRI) (units = grams)
Time frame: 18 months
LV cellular component as determined by cMRI (units = % of total LV mass)
Time frame: 12 months
LV cellular component as determined by cMRI (units = % of total LV mass)
Time frame: 18 months
LV extracellular component as determined by cMRI (units = % of total LV mass)
Time frame: 12 months
LV extracellular component as determined by cMRI (units = % of total LV mass)
Time frame: 18 months
Extent of cMRI late gadolinium enhancement of the LV (unites = % of area)
Time frame: 12 months
Extent of cMRI late gadolinium enhancement of the LV (unites = % of area)
Time frame: 18 months
LV mass measurement by Cardiac MRI (cMRI) (units = grams)
Time frame: Month 12
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rodney H Falk, MD principal investigator
Brigham and Women's Hospital
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Isis 420915/GSK 299872 in people with Amyloidosis, run by Brigham and Women's Hospital.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 10 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Systolic strain imaging by echocardiographic speckle tracking (time frame: Month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2016.