Hypertrophic Cardiomyopathy (HCM)PRO-Gene MavaNCT07408427
Precision Pharmacogenetics and Genotype Class Based Prediction of Mavacamten Response in Obstructive Hypertrophic Cardiomyopathy
An observational study of Hypertrophic Cardiomyopathy (HCM), run by University of Manchester at 1 site in United Kingdom.
Trial summary
This research study, aims to understand why a specific heart medication called mavacamten works better for some people with hypertrophic cardiomyopathy (HCM) than for others. We believe the answer might be in our genes. The study focuses on two key areas: 1. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Hypertrophic Cardiomyopathy (HCM)
- What is being tested?
- Observational study, no new intervention offered
- How many people
- 140 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jun 2026to Dec 2029
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study will enroll adult patients with a diagnosis of symptomatic obstructive hypertrophic cardiomyopathy (oHCM). The target population consists of individuals who are either currently receiving mavacamten as part of their standard clinical care or are candidates for initiating therapy. Participants will be recruited from the specialist Inherited Cardiac Conditions (ICC) clinic at the study site.
Who may be able to join
- Participants above the age of 18 years, with a confirmed diagnosis of oHCM, not solely explained by abnormal loading conditions (e.g. significant hypertension, valvular disease).
Who cannot join
- HCM phenocopies (e.g., amyloid, Fabry's disease)
- Prior septal reduction therapy (within 6 months)
- Contraindications to mavacamten (e.g., baseline LVEF < 55%, pregnancy, uncontrolled heart failure)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site
Manchester Centre for Genomic Medicine (MCGM)
Multiple Locations
Wei Jun How, +441619987070, weijun.how@manchester.ac.uk
William Newman
About this study
This research study, aims to understand why a specific heart medication called mavacamten works better for some people with hypertrophic cardiomyopathy (HCM) than for others. We believe the answer might be in our genes.
The study focuses on two key areas:
- The specific gene causing HCM:The study will investigate whether the type of gene causing the condition in a person influences how well mavacamten works for them.
- Each individual carry a certain gene that helps metabolise and process medication (otherwise known as pharmacogenetics). Our research will closely examine a gene called CYP2C19 to see if a person's natural processing speed (slow, normal, or fast) affects the medicine's performance. The study will also look for rare genetic variations that standard tests might miss.
Read the detailed description
The PRO-Gene Mava study is a prospective, observational cohort study designed to investigate the genetic and pharmacogenomic determinants of response to mavacamten in adults with obstructive hypertrophic cardiomyopathy (oHCM). While mavacamten, a cardiac myosin inhibitor, has demonstrated efficacy in reducing left ventricular outflow tract (LVOT) obstruction, significant inter-individual variability in clinical response exists.
This study is predicated on two primary hypotheses:
- Genotype-Dependent Efficacy: Pre-clinical data suggest mavacamten's mechanism of action may be more effective in normalising hypercontractility driven by thick-filament sarcomeric variants (e.g., MYH7) compared to thin-filament variants (e.g., TNNT2, TNNI3), which primarily increase myofilament calcium sensitivity. This study will test this hypothesis in a real-world clinical setting.
- Pharmacogenomic Variability: Mavacamten is metabolised predominantly by CYP2C19. The Summary of Product Characteristics (SmPC) recommends dose adjustments for known poor metabolizers (PMs). However, standard clinical genotyping panels typically only assess common loss-of-function alleles (e.g., *2, *3), potentially misclassifying patients with rare alleles. Furthermore, the clinical impact on intermediate (IM) and ultra-rapid (UM) metabolizers is not well-characterised.The study aims to bridge this knowledge gap by integrating deep genetic data with longitudinal clinical outcomes.
- Conditions
- Hypertrophic Cardiomyopathy (HCM)
- Being tested
- Observational study, no new intervention offered
- Keywords
- hypertrophic cardiomyopathy, pharmacogenetics
- Medical subject headings
- Cardiomyopathy, Hypertrophic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Observational study, no new intervention offeredOther
Observational study, no new intervention offered
| Study group | Role | What they receive |
|---|---|---|
| Observational Cohort of oHCM Patients on Mavacamten | This is a single, prospective, observational cohort of adult patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). Participants are either currently receiving or newly initiating mavacamten as part of their standard clinical care. All treatment decisions, including drug initiation, dosing, and titration, are made by the participant's treating physician and are not influenced by the study protocol. This cohort serves as the population from which clinical, pharmacological, and genomic data will be collected for analysis. Receives: Other: Observational study, no new intervention offered |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in echocardiographic measure (LVOT gradient)
To assess the change in LVOT gradient (mmHg) following treatment with myosin inhibitors (mavacamten) according to genotype class and CYP2C19 status
Measured: 6 months
Secondary outcomes (2)
Change in LVEF in response to mavacamten
Change in LVEF in response to mavacamten (%), in particular, temporary discontinuation of the medication due to significant decline in LVEF <50%, depending on metaboliser status and genotype class
Measured: 6 months
Cardiac Biomarker Response Depending on Genotype
To assess change in serum biomarkers (cardiac troponin and nT-proBNP) according to genotype class and CYP2C19 status in response to mavacamten
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2026
- Study startJun 2026 (estimated)
- Primary completionJun 2029 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypertrophic Cardiomyopathy (HCM)Studies of the same condition, open and under way.
- More trials run by University of ManchesterThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Manchester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Wei Jun How, University of Manchester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07408427
- Sponsor's protocol ID
- 368062
- Acronym
- PRO-Gene Mava
- Status last verified
- Feb 2026
- First submitted
- 6 Feb 2026
- Last updated
- 13 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Precision Pharmacogenetics and Genotype Class Based Prediction of Mavacamten Response in Obstructive Hypertrophic Cardiomyopathy
- ClinicalTrials.gov ID
- NCT07408427
- Acronym / sponsor ID
- PRO-Gene Mava / 368062
- Conditions
- Hypertrophic Cardiomyopathy (HCM)
- Keywords
- hypertrophic cardiomyopathy, pharmacogenetics
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- University of ManchesterUniversity, hospital or other
- Study start
- Jun 2026 (estimated)
- Primary completion
- Jun 2029 (estimated)
- Study completion
- Dec 2029 (estimated)
- First posted
- 13 Feb 2026 (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.
This research study, aims to understand why a specific heart medication called mavacamten works better for some people with hypertrophic cardiomyopathy (HCM) than for others. We believe the answer might be in our genes.
The study focuses on two key areas:
- The specific gene causing HCM:The study will investigate whether the type of gene causing the condition in a person influences how well mavacamten works for them.
- Each individual carry a certain gene that helps metabolise and process medication (otherwise known as pharmacogenetics). Our research will closely examine a gene called CYP2C19 to see if a person's natural processing speed (slow, normal, or fast) affects the medicine's performance. The study will also look for rare genetic variations that standard tests might miss.
Detailed description
The PRO-Gene Mava study is a prospective, observational cohort study designed to investigate the genetic and pharmacogenomic determinants of response to mavacamten in adults with obstructive hypertrophic cardiomyopathy (oHCM). While mavacamten, a cardiac myosin inhibitor, has demonstrated efficacy in reducing left ventricular outflow tract (LVOT) obstruction, significant inter-individual variability in clinical response exists.
This study is predicated on two primary hypotheses:
- Genotype-Dependent Efficacy: Pre-clinical data suggest mavacamten's mechanism of action may be more effective in normalising hypercontractility driven by thick-filament sarcomeric variants (e.g., MYH7) compared to thin-filament variants (e.g., TNNT2, TNNI3), which primarily increase myofilament calcium sensitivity. This study will test this hypothesis in a real-world clinical setting.
- Pharmacogenomic Variability: Mavacamten is metabolised predominantly by CYP2C19. The Summary of Product Characteristics (SmPC) recommends dose adjustments for known poor metabolizers (PMs). However, standard clinical genotyping panels typically only assess common loss-of-function alleles (e.g., *2, *3), potentially misclassifying patients with rare alleles. Furthermore, the clinical impact on intermediate (IM) and ultra-rapid (UM) metabolizers is not well-characterised.The study aims to bridge this knowledge gap by integrating deep genetic data with longitudinal clinical outcomes.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Observational Cohort of oHCM Patients on Mavacamten | – | Other: Observational study, no new intervention offeredThis is a single, prospective, observational cohort of adult patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM). Participants are either currently receiving or newly initiating mavacamten as part of their standard clinical care. All treatment decisions, including drug initiation, dosing, and titration, are made by the participant's treating physician and are not influenced by the study protocol. This cohort serves as the population from which clinical, pharmacological, and genomic data will be collected for analysis. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study will enroll adult patients with a diagnosis of symptomatic obstructive hypertrophic cardiomyopathy (oHCM). The target population consists of individuals who are either currently receiving mavacamten as part of their standard clinical care or are candidates for initiating therapy. Participants will be recruited from the specialist Inherited Cardiac Conditions (ICC) clinic at the study site.
Key inclusion criteria (1 listed)
- Participants above the age of 18 years, with a confirmed diagnosis of oHCM, not solely explained by abnormal loading conditions (e.g. significant hypertension, valvular disease).
Key exclusion criteria (3 listed)
- HCM phenocopies (e.g., amyloid, Fabry's disease)
- Prior septal reduction therapy (within 6 months)
- Contraindications to mavacamten (e.g., baseline LVEF < 55%, pregnancy, uncontrolled heart failure)
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 |
|---|---|---|
| Observational study, no new intervention offeredObservational study, no new intervention offered | Other | Observational Cohort of oHCM Patients on Mavacamten |
Primary outcome
Change in echocardiographic measure (LVOT gradient)
Time frame: 6 months
To assess the change in LVOT gradient (mmHg) following treatment with myosin inhibitors (mavacamten) according to genotype class and CYP2C19 status
2 secondary outcomes
Change in LVEF in response to mavacamten
Time frame: 6 months
Cardiac Biomarker Response Depending on Genotype
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2026.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypertrophic Cardiomyopathy (HCM), run by University of Manchester at 1 site in United Kingdom.
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 1 inclusion and 3 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: opening soon, as of the sponsor's last update on 13 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 Kingdom. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wei Jun How (+441619987070, weijun.how@manchester.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in echocardiographic measure (LVOT gradient) (time frame: 6 months). 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 13 Feb 2026.