LMNA-Related Dilated CardiomyopathyPhase 2NCT02057341
A Study of ARRY-371797 in Patients With LMNA-Related Dilated Cardiomyopathy
A Phase 2 study testing ARRY-371797, p38 inhibitor; oral in people with LMNA-Related Dilated Cardiomyopathy, run by Pfizer at 6 sites in United States.
Trial summary
This is a Phase 2 pilot study, involving a 48-week treatment period, designed to test the effectiveness of investigational study drug ARRY-371797 in treating patients with symptomatic genetic dilated cardiomyopathy due to a lamin A/C gene mutation, and to further evaluate the drug's safety. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- LMNA-Related Dilated Cardiomyopathy
- What is being tested?
- ARRY-371797, p38 inhibitor; oral
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 6 sitesUnited States
- Study dates
- Feb 2014to May 2016
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with idiopathic dilated cardiomyopathy and stable New York Heart Association (NYHA) Class II - IIIa congestive heart failure (CHF).
- Stable, guidelines-based medical and device therapy, without any CHF hospitalizations or change in heart failure drug dose with ≥ 50% reduction in dose or ≥ 100% increase in dose in the past 3 months.
- Left ventricular (LV) end diastolic diameter by trans-thoracic echocardiography of > 3.3 cm/m2 (for females) or 3.4 cm/m2 (for males) and/or LV ejection fraction ≤ 45%.
- Gene positive for a pathogenic mutation in the LMNA gene, as determined by a CLIA-certified clinical laboratory (mutations including but not limited to: splice-site, non-sense, deletion mutations, a mis-sense mutation in a highly conserved codon, a mis-sense mutation involving a major charge change, a mis-sense mutation previously associated with genetic dilated cardiomyopathy).
- Within 3 weeks prior to first dose of study drug, completed distance during six minute walk test of ≥ 100 m and ≤ 350 m AND/OR ≥ 100 m and ≤ 450 m AND ≤ 60% predicted distance AND patient is symptomatic for dilated cardiomyopathy per Investigator judgment.
- On the day before and day of first dose of study drug, completed distance during six minute walk test of ≥ 100 m and ≤ 400 m (with the greater value within 10% of the lesser value) AND/OR ≥ 100 m and ≤ 475 m (with the greater value within 10% of the lesser value) AND patient is symptomatic for dilated cardiomyopathy per Investigator judgment.
- Acceptable hematology, hepatic and renal function laboratory values within 3 weeks prior to first dose of study drug.
- Additional criteria exist.
Who cannot join
- Unstable clinical cardiac symptoms requiring unscheduled hospitalization within 60 days prior to study start.
- Clinically significant coronary artery disease, as per Investigator judgment.
- Currently receiving continuous intravenous (IV) inotrope infusion, or presence of a ventricular assist device, or history of prior heart transplantation.
- Any of the following within 60 days prior to study start: Myocardial infarction, cardiac surgical procedures, acute coronary syndrome, hemodynamically destabilizing cardiac arrhythmia, serious systemic infection with evidence of septicemia, any major surgical procedure requiring general anesthesia.
- Uncorrected, hemodynamically significant primary valvular disease.
- Initiation of cardiac resynchronization therapy within 180 days prior to study start.
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- Likelihood, in the Investigator's opinion, of undergoing cardiac transplantation, left ventricular assist device or other device implantation, or other cardiac surgery within the next 6 months; or of requiring continuous IV inotropic treatment, or referral for hospice or end-of-life treatment.
- Active malignancy (except surgically-curative basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma).
- Receiving chronic immunosuppressant therapy.
- Known positive serology for the human immunodeficiency virus (HIV), active hepatitis B and/or hepatitis C.
- Participation in any other investigational study of drugs or devices within 30 days prior to study start.
- Additional criteria exist.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
University of Colorado School of Medicine
Aurora, Colorado, 80045
Johns Hopkins University
Baltimore, Maryland, 21205
Brigham and Women's Hospital
Boston, Massachusetts, 02115
The Ohio State University
Columbus, Ohio, 43210
Meriter Wisconsin Heart
Madison, Wisconsin, 53713
Stanford University School of Medicine
Stanford, California, 94305
About this study
This is a Phase 2 pilot study, involving a 48-week treatment period, designed to test the effectiveness of investigational study drug ARRY-371797 in treating patients with symptomatic genetic dilated cardiomyopathy due to a lamin A/C gene mutation, and to further evaluate the drug's safety. Approximately 12 patients from the US will be enrolled in this study.
- Conditions
- LMNA-Related Dilated Cardiomyopathy
- Being tested
- ARRY-371797, p38 inhibitor; oral
- Keywords
- laminopathy
- Medical subject headings
- Cardiomyopathy, Dilated, Laminopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ARRY-371797, p38 inhibitor; oralDrug
multiple dose, single schedule
| Study group | Role | What they receive |
|---|---|---|
| ARRY-371797 (Dose 1) | Experimental | Not described Receives: Drug: ARRY-371797, p38 inhibitor; oral |
| ARRY-371797 (Dose 2) | Experimental | Not described Receives: Drug: ARRY-371797, p38 inhibitor; oral |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assess the efficacy of the study drug in terms of change from Baseline in 6-minute walk test.
Measured: 12 weeks
Secondary outcomes (4)
Assess the efficacy of study drug in terms of left ventricular function.
Measured: 48 weeks
Assess the efficacy of study drug in terms of right ventricular function.
Measured: 48 weeks
Assess the safety of study drug in terms of adverse events, clinical laboratory tests and electrocardiograms.
Measured: 48 weeks
Characterize the pharmacokinetics (PK) of study drug and metabolites in terms of plasma concentration-time profiles and model-based PK parameters.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Feb 2014 (estimated)
- Study startFeb 2014
- Primary completionMay 2016
- Study completionMay 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for LMNA-Related Dilated CardiomyopathyStudies of the same condition, open and under way.
- More trials run by PfizerThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02057341
- Sponsor's protocol ID
- ARRAY-797-231
- Other IDs
- C4411004
- Status last verified
- Oct 2020
- First submitted
- 5 Feb 2014
- Last updated
- 14 Oct 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Garcia-Pavia P, Palomares JFR, Sinagra G, Barriales-Villa R, Lakdawala NK, Gottlieb RL, Goldberg RI, Elliott P, Lee P, Li H, Angeli FS, Judge DP, MacRae CA; REALM-DCM Investigators. REALM-DCM: A Phase 3, Multinational, Randomized, Placebo-Controlled Trial of ARRY-371797 in Patients With Symptomatic LMNA-Related Dilated Cardiomyopathy. Circ Heart Fail. 2024 Jul;17(7):e011548. doi: 10.1161/CIRCHEARTFAILURE.123.011548. Epub 2024 Jul 9.
PubMed 38979608Judge DP, Taylor MR, Li H, Oliver C, Angeli FS, Lee PA, MacRae CA. Long-term effectiveness of ARRY-371797 in people with dilated cardiomyopathy and a faulty LMNA gene: a plain language summary. Future Cardiol. 2023 Mar;19(3):117-126. doi: 10.2217/fca-2022-0125. Epub 2023 Apr 3.
PubMed 37010012MacRae CA, Taylor MR, Mestroni L, Moses J, Ashley EA, Wheeler MT, Lakdawala NK, Hershberger RE, Sandor V, Saunders ME, Oliver C, Lee PA, Judge DP. Plain Language Summary of Publication of the safety and efficacy of ARRY-371797 in people with dilated cardiomyopathy and a faulty LMNA gene. Future Cardiol. 2023 Feb;19(2):55-63. doi: 10.2217/fca-2022-0099. Epub 2023 Jan 31.
PubMed 36718638MacRae CA, Taylor MRG, Mestroni L, Moses J, Ashley EA, Wheeler MT, Lakdawala NK, Hershberger RE, Sandor V, Saunders ME, Oliver C, Lee PA, Judge DP. Efficacy and Safety of ARRY-371797 in LMNA-Related Dilated Cardiomyopathy: A Phase 2 Study. Circ Genom Precis Med. 2023 Feb;16(1):e003730. doi: 10.1161/CIRCGEN.122.003730. Epub 2022 Dec 14.
PubMed 36515663
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of ARRY-371797 in Patients With LMNA-Related Dilated Cardiomyopathy
- ClinicalTrials.gov ID
- NCT02057341
- Acronym / sponsor ID
- ARRAY-797-231
- Conditions
- LMNA-Related Dilated Cardiomyopathy
- Keywords
- laminopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Feb 2014
- Primary completion
- May 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 7 Feb 2014 (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.
This is a Phase 2 pilot study, involving a 48-week treatment period, designed to test the effectiveness of investigational study drug ARRY-371797 in treating patients with symptomatic genetic dilated cardiomyopathy due to a lamin A/C gene mutation, and to further evaluate the drug's safety. Approximately 12 patients from the US will be enrolled in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ARRY-371797 (Dose 1) | Experimental | Drug: ARRY-371797, p38 inhibitor; oral |
| ARRY-371797 (Dose 2) | Experimental | Drug: ARRY-371797, p38 inhibitor; oral |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with idiopathic dilated cardiomyopathy and stable New York Heart Association (NYHA) Class II - IIIa congestive heart failure (CHF).
- Stable, guidelines-based medical and device therapy, without any CHF hospitalizations or change in heart failure drug dose with ≥ 50% reduction in dose or ≥ 100% increase in dose in the past 3 months.
- Left ventricular (LV) end diastolic diameter by trans-thoracic echocardiography of > 3.3 cm/m2 (for females) or 3.4 cm/m2 (for males) and/or LV ejection fraction ≤ 45%.
- Gene positive for a pathogenic mutation in the LMNA gene, as determined by a CLIA-certified clinical laboratory (mutations including but not limited to: splice-site, non-sense, deletion mutations, a mis-sense mutation in a highly conserved codon, a mis-sense mutation involving a major charge change, a mis-sense mutation previously associated with genetic dilated cardiomyopathy).
- Within 3 weeks prior to first dose of study drug, completed distance during six minute walk test of ≥ 100 m and ≤ 350 m AND/OR ≥ 100 m and ≤ 450 m AND ≤ 60% predicted distance AND patient is symptomatic for dilated cardiomyopathy per Investigator judgment.
Key exclusion criteria (12 listed)
- Unstable clinical cardiac symptoms requiring unscheduled hospitalization within 60 days prior to study start.
- Clinically significant coronary artery disease, as per Investigator judgment.
- Currently receiving continuous intravenous (IV) inotrope infusion, or presence of a ventricular assist device, or history of prior heart transplantation.
- Any of the following within 60 days prior to study start: Myocardial infarction, cardiac surgical procedures, acute coronary syndrome, hemodynamically destabilizing cardiac arrhythmia, serious systemic infection with evidence of septicemia, any major surgical procedure requiring general anesthesia.
- Uncorrected, hemodynamically significant primary valvular 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 |
|---|---|---|
| ARRY-371797, p38 inhibitor; oralmultiple dose, single schedule | Drug | ARRY-371797 (Dose 1), ARRY-371797 (Dose 2) |
Primary outcome
Assess the efficacy of the study drug in terms of change from Baseline in 6-minute walk test.
Time frame: 12 weeks
4 secondary outcomes
Assess the efficacy of study drug in terms of left ventricular function.
Time frame: 48 weeks
Assess the efficacy of study drug in terms of right ventricular function.
Time frame: 48 weeks
Assess the safety of study drug in terms of adverse events, clinical laboratory tests and electrocardiograms.
Time frame: 48 weeks
Characterize the pharmacokinetics (PK) of study drug and metabolites in terms of plasma concentration-time profiles and model-based PK parameters.
Time frame: 48 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2020.
- Derived from this study: PubMed 38979608Garcia-Pavia P, Palomares JFR, Sinagra G, Barriales-Villa R, Lakdawala NK, Gottlieb RL, Goldberg RI, Elliott P, Lee P, Li H, Angeli FS, Judge DP, MacRae CA; REALM-DCM Investigators. REALM-DCM: A Phase 3, Multinational, Randomized, Placebo-Controlled Trial of ARRY-371797 in Patients With Symptomatic LMNA-Related Dilated Cardiomyopathy. Circ Heart Fail. 2024 Jul;17(7):e011548. doi: 10.1161/CIRCHEARTFAILURE.123.011548. Epub 2024 Jul 9.
- Derived from this study: PubMed 37010012Judge DP, Taylor MR, Li H, Oliver C, Angeli FS, Lee PA, MacRae CA. Long-term effectiveness of ARRY-371797 in people with dilated cardiomyopathy and a faulty LMNA gene: a plain language summary. Future Cardiol. 2023 Mar;19(3):117-126. doi: 10.2217/fca-2022-0125. Epub 2023 Apr 3.
- Derived from this study: PubMed 36718638MacRae CA, Taylor MR, Mestroni L, Moses J, Ashley EA, Wheeler MT, Lakdawala NK, Hershberger RE, Sandor V, Saunders ME, Oliver C, Lee PA, Judge DP. Plain Language Summary of Publication of the safety and efficacy of ARRY-371797 in people with dilated cardiomyopathy and a faulty LMNA gene. Future Cardiol. 2023 Feb;19(2):55-63. doi: 10.2217/fca-2022-0099. Epub 2023 Jan 31.
- Derived from this study: PubMed 36515663MacRae CA, Taylor MRG, Mestroni L, Moses J, Ashley EA, Wheeler MT, Lakdawala NK, Hershberger RE, Sandor V, Saunders ME, Oliver C, Lee PA, Judge DP. Efficacy and Safety of ARRY-371797 in LMNA-Related Dilated Cardiomyopathy: A Phase 2 Study. Circ Genom Precis Med. 2023 Feb;16(1):e003730. doi: 10.1161/CIRCGEN.122.003730. Epub 2022 Dec 14.
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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.
Pfizer CT.gov Call Center study director
Pfizer
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ARRY-371797, p38 inhibitor; oral in people with LMNA-Related Dilated Cardiomyopathy, run by Pfizer at 6 sites 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 8 inclusion and 12 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: finished, as of the sponsor's last update on 14 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Assess the efficacy of the study drug in terms of change from Baseline in 6-minute walk test. (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02057341, which also lists 4 linked publications.
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 14 Oct 2020.