Clinical Trial of a MEK Inhibitor for RASopathy-Associated Severe Infantile Hypertrophic Cardiomyopathy: Baby MERIT

NCT07817186 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 21067 Baby MERIT
• Study Type: interventional
• Target: 25
• Locations: 0 countries
• Sites: N/A

Brief Summary

This project seeks to perform a Phase 3 clinical trial to test whether an FDA-approved cancer drug called trametinib is effective in treating young infants with genetic conditions called RASopathies and a severe, life-threatening heart problem called hypertrophic cardiomyopathy. The purpose of this research is to demonstrate that trametinib is effective in preventing these sick babies from dying, receiving a heart transplant or undergoing heart surgery to remove extra heart muscle over a one-year period. In addition, the investigators will determine how often this heart problem comes back when the trametinib treatment is stopped.

Conditions

HCM; Heart Failure (Pediatric); Noonan Syndrome and Other Rasopathy

Keywords

Noonan Syndrome; RAS-HCM; RASopathy; Heart failure; trametinib; MEK inhibitor

Outcome Measures

Primary Outcomes (1)

• Time to first occurrence of death, heart transplantation, or LV septal myectomy to relieve LV outflow tract obstruction

  This is a composite time-to-event outcome. An event is defined as the first occurrence of any of the following: death, heart transplantation, or LV septal myectomy to relieve LV outflow tract obstruction. For participants experiencing more than one component event, only the first event contributes to the primary endpoint. Participants who do not experience any component event are censored according to the prespecified analysis rules. The treatment arms will be compared using Kaplan-Meier methods and the log-rank test.

  From qualifying hospital admission through 12 months after the qualifying hospital admission

Secondary Outcomes (7)

• Time from qualifying hospital admission to death

  From qualifying hospital admission through 12 months after the qualifying hospital admission

• Change from baseline in LV posterior wall thickness z-score at 12 months

  Baseline and 12 months after qualifying hospital admission

• Ross class at 12 months

  12 months after qualifying hospital admission

• Change from baseline in log-transformed BNP at 12 months

  Baseline and 12 months after qualifying hospital admission

• Time to first occurrence of death, heart transplantation, or LV septal myectomy to relieve LV outflow tract obstruction

  From qualifying hospital admission through 24 months after the qualifying hospital admission

Study Arms (1)

Treatment

EXPERIMENTAL

Drug: Trametinib

Interventions

Trametinib DRUG

Participants will begin 0.025 mg/kg of oral trametinib once daily for up to 12 months. Dose will be adjusted for weight at each study visit. A 12-month surveillance phase follows cessation of treatment. If the participant experiences a RAS-HCM relapse during the surveillance phase, they will restart oral trametinib once daily for up to 12 additional months.

Treatment

Eligibility Criteria

• Age: 28 Days - 6 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Molecular genetic diagnosis of a RASopathy signaling through the RAS/MAPK pathway as identified by molecular assays performed in a Clinical Laboratory Improvements of 1988 (CLIA) or similarly certified laboratories. Qualifying genotypes will included variants in any gene causing Noonan, Costello or cardiofaciocutaneous syndrome curated as pathogenic or likely pathogenic and consistent with the genetic mechanism (i.e., one allele in genes acting in an autosomal dominant manner and two alleles in trans for the autosomal recessive form of LZTR1-related Noonan syndrome).
• Diagnosis of HCM, as defined by LV and interventricular septal wall thickness with a z-score \> 2 by echocardiography
• Age ≥ 28 days and ≤ 6 months
• Ross classification of HF of III or IV
• Hospitalization
• In the opinion of the site investigator, ability to comply with study protocol requirements
• Signed informed consent for the trial by a parent or legal guardian

You may not qualify if:

• PTPN11 pathogenic/likely pathogenic variants causing NSML
• Prior treatment with a MEK inhibitor
• Requiring treatment with strong inhibitors of CYP2C19 and CYP3A4, strong inducers of CYP3A4, and substrates of CYP2C9 with a narrow therapeutic index
• Platelet count \< 50,000/µL
• Neoplastic disorder requiring treatment (e.g., juvenile myelomonocytic leukemia)

Sponsors & Collaborators

• Carelon Research: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

MeSH Terms

Conditions

Noonan Syndrome; Heart Failure

Interventions

trametinib

Condition Hierarchy (Ancestors)

Craniofacial Abnormalities; Musculoskeletal Abnormalities; Musculoskeletal Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: Echocardiographic studies will be reviewed centrally by the Echocardiography Core Laboratory at Boston Children's Hospital under a workflow that blinds the reader to treatment assignment and participant identity.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2026
• First Posted: September 14, 2026
• Study Start (Estimated): August 1, 2027
• Primary Completion (Estimated): June 30, 2032
• Study Completion (Estimated): June 30, 2032
• Last Updated: September 14, 2026

Record last verified: 2026-07