Clinical trial NCT04349072: A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive HCM Who Are Eligible for Septal Reduction Therapy
Official title: A Randomized, Double-blind, Placebo-controlled Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HOCM, Hypertrophic Obstructive Cardiomyopathy
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2020-04-16
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a parallel group treatment study with 2 treatment groups; subjects and investigators are blinded to treatment and dose for the first 16 weeks of treatment. Mavacamten dose is blinded throughout the study.
Primary purpose: TREATMENT

Brief summary: This is a randomized, double-blind, placebo-controlled, multi-center study in the United States (U.S.) that will evaluate the effect of mavacamten treatment on reducing the number of septal reduction therapy (SRT) procedures performed in subjects with symptomatic obstructive hypertrophic cardiomyopathy (oHCM \[also known as HOCM\]) who are eligible for SRT based on ACCF/AHA 2011 and/or ESC 2014 guidelines.


Eligibility criteria: Key Inclusion Criteria:

* At least 18 years old at screening and body weight \> 45 kg at screening
* Diagnosed with oHCM consistent with current ACCF/AHA 2011 and meet their recommendations for invasive therapies
* Referred or under active consideration within the past 12 months for SRT procedure and willing to have SRT procedure
* Has documented left ventricular ejection fraction (LVEF) ≥ 60% at Screening
* Has documented oxygen saturation at rest ≥ 90% at Screening

Key Exclusion Criteria:

* Persistent or permanent atrial fibrillation and subject not on anticoagulation for ≥ 4 weeks prior to screening and/or not adequately rate controlled ≤ 6 months prior to screening
* Previously treated with invasive septal reduction (surgical myectomy or percutaneous alcohol septal ablation \[ASA\])
* For individuals on beta blockers, calcium channel blockers, or disopyramide, any dose adjustment of these medications \< 14 days prior to screening or an anticipated change in regimen during the first 16 weeks of the study
* Any medical condition that precludes upright exercise stress testing
* Paroxysmal, intermittent atrial fibrillation with atrial fibrillation present at screening
* Prior treatment with cardiotoxic agents, such as doxorubicin or similar
* Has a history or evidence of any other clinically significant disorder, condition, or disease that would pose a risk to subject safety or interfere with the study evaluation, procedures, or completion

Primary outcomes:
measure: Composite of Decision to Proceed With Septal Reduction Therapy (SRT) and SRT Guideline Eligible at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Number of Participants With at Least One Class Improvement From Baseline in New York Heart Association (NYHA) Class at Week 16
timeFrame: Baseline and week 16
measure: Change From Baseline to Week 16 in Kansas City Cardiomyopathy Questionnaire 23-item Version, Clinical Summary Score (KCCQ-23, CSS)
timeFrame: Baseline and week 16
measure: Change From Baseline to Week 16 in N-Terminal Pro-b-Type Natriuretic Peptide (NT-proBNP)
timeFrame: Baseline and week 16
measure: Change From Baseline to Week 16 in Cardiac Troponin
timeFrame: Baseline and week 16
measure: Change From Baseline to Week 16 in Post-Exercise Left Ventricular Outflow Tract (LVOT) Gradient
timeFrame: Baseline and week 16
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Local Institution - 0009
state: California
city: Stanford
country: United States
facility: Local Institution - 0011
state: California
city: New Haven
country: United States
facility: Local Institution - 0001
state: Connecticut
city: Weston
country: United States
facility: Local Institution - 0021
state: Florida
city: Boston
country: United States
facility: Local Institution - 0016
state: Massachusetts
city: Boston
country: United States
facility: Local Institution - 0007
state: Massachusetts
city: Ann Arbor
country: United States
facility: Local Institution - 0006
state: Michigan
city: Grand Rapids
country: United States
facility: Local Institution - 0013
state: Michigan
city: Rochester
country: United States
facility: Local Institution - 0015
state: Minnesota
city: Saint Louis
country: United States
facility: Local Institution - 0005
state: Missouri
city: New York
country: United States
facility: Local Institution - 0010
state: New York
city: Valhalla
country: United States
facility: Local Institution - 0017
state: New York
city: Durham
country: United States
facility: Local Institution - 0004
state: North Carolina
city: Cleveland
country: United States
facility: Local Institution - 0020
state: Ohio
city: Portland
country: United States
facility: Local Institution - 0002
state: Oregon
city: Philadelphia
country: United States
facility: Local Institution - 0003
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Local Institution - 0019
state: Pennsylvania
city: Nashville
country: United States
facility: Local Institution - 0014
state: Tennessee
city: Nashville
country: United States
facility: Local Institution - 0018
state: Tennessee
city: Houston
country: United States
facility: Local Institution
state: Texas
city: Murray
country: United States
facility: Local Institution - 0012
state: Utah
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_DIRECTOR
References:
citation: Desai MY, Owens A, Geske JB, Wolski K, Saberi S, Wang A, Sherrid M, Cremer PC, Naidu SS, Smedira NG, Schaff H, McErlean E, Sewell C, Balasubramanyam A, Lampl K, Sehnert AJ, Nissen SE. Dose-Blinded Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy: Outcomes Through 32 Weeks. Circulation. 2023 Mar 14;147(11):850-863. doi: 10.1161/CIRCULATIONAHA.122.062534. Epub 2022 Nov 6.
citation: Desai MY, Owens A, Geske JB, Wolski K, Naidu SS, Smedira NG, Cremer PC, Schaff H, McErlean E, Sewell C, Li W, Sterling L, Lampl K, Edelberg JM, Sehnert AJ, Nissen SE. Myosin Inhibition in Patients With Obstructive Hypertrophic Cardiomyopathy Referred for Septal Reduction Therapy. J Am Coll Cardiol. 2022 Jul 12;80(2):95-108. doi: 10.1016/j.jacc.2022.04.048.
citation: Zampieri M, Argiro A, Marchi A, Berteotti M, Targetti M, Fornaro A, Tomberli A, Stefano P, Marchionni N, Olivotto I. Mavacamten, a Novel Therapeutic Strategy for Obstructive Hypertrophic Cardiomyopathy. Curr Cardiol Rep. 2021 Jun 3;23(7):79. doi: 10.1007/s11886-021-01508-0.
citation: Desai MY, Wolski K, Owens A, Naidu SS, Geske JB, Smedira NG, Schaff H, Lampl K, McErlean E, Sewell C, Zhang D, Edelberg JM, Sehnert AJ, Nissen SE. Study design and rationale of VALOR-HCM: evaluation of mavacamten in adults with symptomatic obstructive hypertrophic cardiomyopathy who are eligible for septal reduction therapy. Am Heart J. 2021 Sep;239:80-89. doi: 10.1016/j.ahj.2021.05.007. Epub 2021 May 24.