AmyloidosisPhase 2NCT03702829
24 Month Open Label Study of the Tolerability and Efficacy of Inotersen in TTR Amyloid Cardiomyopathy Patients
A Phase 2 study testing Inotersen in people with Amyloidosis, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
Transthyretin is a protein produced in the liver that transports thyroid hormone and vitamin A. A single substitution of an amino acid in the structure of TTR can result in a relatively unstable protein, the breakdown products of which (predominantly monomers) aggregate abnormally and produce proteinaceous deposits in… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Amyloidosis
- What is being tested?
- Inotersen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Feb 2019to 15 Jan 2022
- 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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have ATTR amyloidosis, defined as is defined as an echocardiographic appearance of left ventricular wall thickness of 13 mm or more, in the absence of uncontrolled hypertension, and with EITHER a positive biopsy for amyloid, which also stains positive for TTR by immunochemistry or mass spectrometry OR a positive cardiac technetium pyrophosphate scan with isotope uptake in the heart equal or greater to rib uptake and with no evidence of a plasma cell dyscrasia.
- For patients meeting the above criteria, wild-type TTR amyloidosis (ATTRwt)will be defined as having transthyretin genetic sequencing negative for a mutation. Mutant/hereditary TTR (ATTRh) will be defined as TTR amyloid cardiomyopathy with TTR sequencing showing an amyloidogenic mutation. A positive biopsy can be from any organ, providing that the echocardiographic appearance is typical of amyloidosis.
- 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 18-85 years
- Male, or non-pregnant, non-lactating females. If a woman is premenopausal, or 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
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- If diagnosis is made by tissue biopsy histochemical diagnosis (positive stains for TTR in absence of staining for light chains, or AA amyloid) in the presence of green birefringent material in Congo red-stained tissue specimens or sulfated Alcian blue stain typical for amyloid deposition. NB. All patients will have had a definitive diagnosis of TTR amyloidosis made prior to study entry, either by tissue biopsy or positive PYP scan, and all will have been genotyped. No further diagnostic testing will need to be done at or after study entry.
- If diagnosis is made by nuclear imaging, a positive technetium pyrophosphate scan, characterized by isotope uptake in the heart of an intensity equal to or greater than, rib uptake.
- 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.
- Willingness to take daily oral Vitamin A supplementation throughout the study and for 3 months thereafter.
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 despite optimal heart failure management.
- 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), or ongoing non-cardiac disease that, in the opinion of the investigator, will likely need hospitalization over the next 2 years (e.g. active cancer) .
- Prior liver transplantation or liver transplantation anticipated in less than 6 months
- ALT and/or AST 2 x ULN and/or Alkaline phosphatase 2 x UNL; Or bilirubin greater than 1.5 times UL (patients with bilirubin ≥1.5 x ULN may be allowed on study if indirect bilirubin only is elevated, ALT/AST is not greater than the ULN and genetic testing confirming Gilbert's disease)
- Glomerular filtration rate (EGFR) < 45 ml/min/1.73m2
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- A history of glomerulonephritis,
- Proteinuria or hematuria as detailed in the section below (immediately following exclusion criteria) entitled "Additional information regarding renal exclusion criteria".
- Platelets less than 125×109/L
- TSH values outside normal range in subjects untreated for thyroid disease, unless mildly elevated with normal T4, and deemed by current standards not to need treatment.
- Uncontrolled hypertension (blood pressure >160/100)
- Acute coronary syndrome or major surgery within 3 months of screening
- Anticipated survival less than 2 years
- Active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to first dose of study drug
- Malignancy within 5 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or prostate that has been successfully treated
- Positive test result for HIV, hepatitis B, or hepatitis C
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: 24 Month Open Label Study of the Tolerability and Efficacy of an Antisense Oligonucleotide (Inotersen) in Patients With Transthyretin (TTR) Amyloid Cardiomyopathy
Transthyretin is a protein produced in the liver that transports thyroid hormone and vitamin A. A single substitution of an amino acid in the structure of TTR can result in a relatively unstable protein, the breakdown products of which (predominantly monomers) aggregate abnormally and produce proteinaceous deposits in nerves and the heart. These deposits are known as amyloid and produce progressive nerve and heart damage. Amyloidosis due to a mutant TTR is usually an autosomal dominant and hence is a familial condition. Wild-type TTR is also capable of producing amyloid deposits which predominantly involves the heart (rather than the nervous system) resulting in a progressive decrease in cardiac function with increasing signs of heart failure. This study aims to determine whether subcutaneous injection of an antisense oligonucleotide drug, known as inotersen, that has been specifically designed to reduce production of the protein transthyretin by the liver, can slow or stop the progression of TTR amyloid cardiomyopathy as compared to historical controls, using advanced echocardiography and cardiac MRI. The study also aims to determine the tolerability and safety of this drug when administered over a 24-month period to patients with TTR amyloid cardiomyopathy.
Read the detailed description
This is an open-label, single center study of 50 patients with cardiac amyloidosis due to wild-type or mutant TTR. Eligible patients will have evidence of cardiac amyloidosis due to transthyretin. The diagnosis will be made by biopsy of the heart or other affected organ with appropriate staining techniques confirming that the amyloid deposits are derived from transthyretin. Alternatively, recent imaging data have shown that a strongly positive nuclear scan using technetium pyrophosphate in the absence of evidence of a plasma cell dyscrasia and in the presence of a typical echocardiographic or cardiac magnetic resonance appearance of cardiac amyloidosis is indicative of TTR amyloidosis and that a biopsy is not needed. This will be acceptable for study entry. As inotersen has been associated with kidney toxicity in a small number of patients, all subjects in the study will be required to have a glomerular filtration rate greater than 45. Once study criteria have been met, and baseline imaging including echocardiography and (where feasible) cardiac magnetic resonance imaging have been performed, all patients will receive inotersen in a weekly 300 mg dosing. Subsequent visits will occur at 6 weeks, and 3, 6, 12, 18 and 24 months. Every 2 weeks, blood will be monitored for renal function and platelet count and urine will be tested by dipstick for proteinuria. Should kidney function be noted to be deteriorating or should proteinuria be found, a more intense renal workup will be performed in order to detect or rule out potential kidney toxicity. At each visit, in addition to standard laboratory work and pregnancy testing if applicable, (complete blood count, comprehensive metabolic panel, thyroid function tests, and urinalysis), Vitamin A level will be drawn (as TTR is a transport protein for Vitamin A) and TTR (prealbumin) level will be drawn to determine degree of suppression. Disease progression will be measured by serial cardiac biomarkers, 6-minute walk, cardiopulmonary stress testing, advanced "strain" echocardiography and cardiac MRI. Patients will be compared to data derived from a historical control group and from data in the literature to determine whether inotersen slows or stops disease progression.
- Conditions
- Amyloidosis
- Being tested
- Inotersen
- Keywords
- wild-type transthyretin amyloidosis, TTR amyloidosis, familial amyloid cardiomyopathy, mutant 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.
InotersenDrug
Also called Antisense Oligonucleotide
Open Label Study
| Study group | Role | What they receive |
|---|---|---|
| Experimental Drug | Experimental | Inotersen, a transthyretin (TTR) antisense oligonucleotide. Administered subcutaneously weekly. Each dose shall contain 300 mg of active drug. Subsequent visits will occur at 3, 6, 12, 18 and 24 months. Every 2 weeks, blood will be monitored for renal function and platelet count and urine will be tested by dipstick for proteinuria. Receives: Drug: Inotersen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Systolic strain imaging by echocardiographic
The primary echocardiographic parameter to be measured will be longitudinal left ventricular (LV) strain (units = % LV longitudinal shortening) as compared to baseline.
Measured: Month 6
Secondary outcomes (9)
Systolic strain evaluation by echocardiography
The primary echocardiographic parameter measured will be longitudinal left ventricular (LV) strain (units = %).
Measured: Month 12
Systolic strain evaluation by echocardiography
The primary echocardiographic parameter measured will be longitudinal left ventricular (LV) strain (units = %).
Measured: Month 18
Systolic strain evaluation by echocardiography
The primary echocardiographic parameter measured will be longitudinal left ventricular (LV) strain (units = %).
Measured: Month 24
LV mass measurement by Cardiac MRI (cMRI) (units = grams)
measurement of LV mass by CMR mapping techniques
Measured: Month 6
LV mass measurement by Cardiac MRI (cMRI) (units = grams)
measurement of LV mass by CMR mapping techniques
Measured: Month 12
LV mass measurement by Cardiac MRI (cMRI) (units = grams)
measurement of LV mass by CMR mapping techniques
Measured: Month 24
ECV-extracellular volume by Cardiac MRI (cMRI) (unit=percentage)
measurement of extracellular volume by CMR T1 mapping techniques
Measured: Month 6
ECV-extracellular volume by Cardiac MRI (cMRI) (unit=percentage)
measurement of extracellular volume by CMR T1 mapping techniques
Measured: Month 12
ECV-extracellular volume by Cardiac MRI (cMRI) (unit=percentage)
measurement of extracellular volume by CMR T1 mapping techniques
Measured: Month 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2018
- Study start28 Feb 2019
- Primary completion31 Dec 2021
- Study completion15 Jan 2022
Why it stopped: recruitment of new patients not possible during Covid 19 epidemic
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
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rodney H. Falk, MD, Brigham and Women's Hospital
- Investigators
- Rodney Falk, MD, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03702829
- Sponsor's protocol ID
- 2018P001436
- Status last verified
- Feb 2026
- First submitted
- 9 Oct 2018
- Last updated
- 20 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 24 Month Open Label Study of the Tolerability and Efficacy of an Antisense Oligonucleotide (Inotersen) in Patients With Transthyretin (TTR) Amyloid Cardiomyopathy
- ClinicalTrials.gov ID
- NCT03702829
- Acronym / sponsor ID
- 2018P001436
- Conditions
- Amyloidosis
- Keywords
- wild-type transthyretin amyloidosis, TTR amyloidosis, familial amyloid cardiomyopathy, mutant transthyretin amyloidosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: recruitment of new patients not possible during Covid 19 epidemic
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Study start
- 28 Feb 2019 (actual)
- Primary completion
- 31 Dec 2021 (actual)
- Study completion
- 15 Jan 2022 (actual)
- First posted
- 11 Oct 2018 (actual)
- 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.
Transthyretin is a protein produced in the liver that transports thyroid hormone and vitamin A. A single substitution of an amino acid in the structure of TTR can result in a relatively unstable protein, the breakdown products of which (predominantly monomers) aggregate abnormally and produce proteinaceous deposits in nerves and the heart. These deposits are known as amyloid and produce progressive nerve and heart damage. Amyloidosis due to a mutant TTR is usually an autosomal dominant and hence is a familial condition. Wild-type TTR is also capable of producing amyloid deposits which predominantly involves the heart (rather than the nervous system) resulting in a progressive decrease in cardiac function with increasing signs of heart failure. This study aims to determine whether subcutaneous injection of an antisense oligonucleotide drug, known as inotersen, that has been specifically designed to reduce production of the protein transthyretin by the liver, can slow or stop the progression of TTR amyloid cardiomyopathy as compared to historical controls, using advanced echocardiography and cardiac MRI. The study also aims to determine the tolerability and safety of this drug when administered over a 24-month period to patients with TTR amyloid cardiomyopathy.
Detailed description
This is an open-label, single center study of 50 patients with cardiac amyloidosis due to wild-type or mutant TTR. Eligible patients will have evidence of cardiac amyloidosis due to transthyretin. The diagnosis will be made by biopsy of the heart or other affected organ with appropriate staining techniques confirming that the amyloid deposits are derived from transthyretin. Alternatively, recent imaging data have shown that a strongly positive nuclear scan using technetium pyrophosphate in the absence of evidence of a plasma cell dyscrasia and in the presence of a typical echocardiographic or cardiac magnetic resonance appearance of cardiac amyloidosis is indicative of TTR amyloidosis and that a biopsy is not needed. This will be acceptable for study entry. As inotersen has been associated with kidney toxicity in a small number of patients, all subjects in the study will be required to have a glomerular filtration rate greater than 45. Once study criteria have been met, and baseline imaging including echocardiography and (where feasible) cardiac magnetic resonance imaging have been performed, all patients will receive inotersen in a weekly 300 mg dosing. Subsequent visits will occur at 6 weeks, and 3, 6, 12, 18 and 24 months. Every 2 weeks, blood will be monitored for renal function and platelet count and urine will be tested by dipstick for proteinuria. Should kidney function be noted to be deteriorating or should proteinuria be found, a more intense renal workup will be performed in order to detect or rule out potential kidney toxicity. At each visit, in addition to standard laboratory work and pregnancy testing if applicable, (complete blood count, comprehensive metabolic panel, thyroid function tests, and urinalysis), Vitamin A level will be drawn (as TTR is a transport protein for Vitamin A) and TTR (prealbumin) level will be drawn to determine degree of suppression. Disease progression will be measured by serial cardiac biomarkers, 6-minute walk, cardiopulmonary stress testing, advanced "strain" echocardiography and cardiac MRI. Patients will be compared to data derived from a historical control group and from data in the literature to determine whether inotersen slows or stops disease progression.
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: InotersenInotersen, a transthyretin (TTR) antisense oligonucleotide. Administered subcutaneously weekly. Each dose shall contain 300 mg of active drug. Subsequent visits will occur at 3, 6, 12, 18 and 24 months. Every 2 weeks, blood will be monitored for renal function and platelet count and urine will be tested by dipstick for proteinuria. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients must have ATTR amyloidosis, defined as is defined as an echocardiographic appearance of left ventricular wall thickness of 13 mm or more, in the absence of uncontrolled hypertension, and with EITHER a positive biopsy for amyloid, which also stains positive for TTR by immunochemistry or mass spectrometry OR a positive cardiac technetium pyrophosphate scan with isotope uptake in the heart equal or greater to rib uptake and with no evidence of a plasma cell dyscrasia.
- For patients meeting the above criteria, wild-type TTR amyloidosis (ATTRwt)will be defined as having transthyretin genetic sequencing negative for a mutation. Mutant/hereditary TTR (ATTRh) will be defined as TTR amyloid cardiomyopathy with TTR sequencing showing an amyloidogenic mutation. A positive biopsy can be from any organ, providing that the echocardiographic appearance is typical of amyloidosis.
- 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 18-85 years
- Male, or non-pregnant, non-lactating females. If a woman is premenopausal, or 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
Key exclusion criteria (21 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 despite optimal heart failure management.
- 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), or ongoing non-cardiac disease that, in the opinion of the investigator, will likely need hospitalization over the next 2 years (e.g. active cancer) .
- Prior liver transplantation or liver transplantation anticipated in less than 6 months
- ALT and/or AST 2 x ULN and/or Alkaline phosphatase 2 x UNL; Or bilirubin greater than 1.5 times UL (patients with bilirubin ≥1.5 x ULN may be allowed on study if indirect bilirubin only is elevated, ALT/AST is not greater than the ULN and genetic testing confirming Gilbert's disease)
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 |
|---|---|---|
| InotersenAlso: Antisense OligonucleotideOpen Label Study | Drug | Experimental Drug |
Primary outcome
Systolic strain imaging by echocardiographic
Time frame: Month 6
The primary echocardiographic parameter to be measured will be longitudinal left ventricular (LV) strain (units = % LV longitudinal shortening) as compared to baseline.
9 secondary outcomes
Systolic strain evaluation by echocardiography
Time frame: Month 12
Systolic strain evaluation by echocardiography
Time frame: Month 18
Systolic strain evaluation by echocardiography
Time frame: Month 24
LV mass measurement by Cardiac MRI (cMRI) (units = grams)
Time frame: Month 6
LV mass measurement by Cardiac MRI (cMRI) (units = grams)
Time frame: Month 12
LV mass measurement by Cardiac MRI (cMRI) (units = grams)
Time frame: Month 24
ECV-extracellular volume by Cardiac MRI (cMRI) (unit=percentage)
Time frame: Month 6
ECV-extracellular volume by Cardiac MRI (cMRI) (unit=percentage)
Time frame: Month 12
ECV-extracellular volume by Cardiac MRI (cMRI) (unit=percentage)
Time frame: Month 24
Results and safety
The study was stopped early (reason given: recruitment of new patients not possible during Covid 19 epidemic). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2026.
- Individual participant dataSharing planned: No
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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 Falk, MD principal investigator
Brigham and Women's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Inotersen in people with Amyloidosis, run by Brigham and Women's Hospital at 1 site in United States.
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 11 inclusion and 21 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: stopped early, as of the sponsor's last update on 20 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 stopped early (reason given: recruitment of new patients not possible during Covid 19 epidemic). Results are not available in the source record.
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 (time frame: Month 6). 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 20 Feb 2026.