RECRUITING

MK-7075 (Miransertib) in Proteus Syndrome

Description

Background: Proteus syndrome is a rare overgrowth disorder. Most people begin to have symptoms between 6 months and 2 years of age. There are very few living adults with this disease. There is also no known treatment for it. Researchers want to see if a new drug can slow down or stop overgrowth in people with Proteus syndrome. Objective: To learn if miransertib is a safe and effective treatment for Proteus syndrome. Eligibility: People ages 3 and older with Proteus syndrome. Design: Participants will be screened with a medical checkup. They will answer questions about their medical history and current health. They will have a physical exam with vital signs. They will have an electrocardiogram to measure their heartbeat. They will give blood and urine samples. They will repeat the screening tests during the study. Participants will take a miransertib pill once a day. They will bring their empty pill bottles with them to the NIH when they visit. If they can t swallow a pill, researchers will try to find other ways for them to take the drug. Participants will have X-rays, ultrasounds, and imaging scans. Photos may be taken of their feet and other parts of the body that have or develop signs of Proteus syndrome. Participants will have lung function tests to measure how much and how fast air moves out of their lungs. Participants will complete surveys about their levels of pain, physical functioning, and quality of life. Participants may have additional tests performed to assess their individual disease. They may have consultations with other specialists. Participation lasts about 4 years. Participants will have 20-30 visits at the NIH.

Study Overview

Study Details

Study overview

Background: Proteus syndrome is a rare overgrowth disorder. Most people begin to have symptoms between 6 months and 2 years of age. There are very few living adults with this disease. There is also no known treatment for it. Researchers want to see if a new drug can slow down or stop overgrowth in people with Proteus syndrome. Objective: To learn if miransertib is a safe and effective treatment for Proteus syndrome. Eligibility: People ages 3 and older with Proteus syndrome. Design: Participants will be screened with a medical checkup. They will answer questions about their medical history and current health. They will have a physical exam with vital signs. They will have an electrocardiogram to measure their heartbeat. They will give blood and urine samples. They will repeat the screening tests during the study. Participants will take a miransertib pill once a day. They will bring their empty pill bottles with them to the NIH when they visit. If they can t swallow a pill, researchers will try to find other ways for them to take the drug. Participants will have X-rays, ultrasounds, and imaging scans. Photos may be taken of their feet and other parts of the body that have or develop signs of Proteus syndrome. Participants will have lung function tests to measure how much and how fast air moves out of their lungs. Participants will complete surveys about their levels of pain, physical functioning, and quality of life. Participants may have additional tests performed to assess their individual disease. They may have consultations with other specialists. Participation lasts about 4 years. Participants will have 20-30 visits at the NIH.

A Multi-Cohort Phase 2 Dose-Escalation Study of MK-7075 (Miransertib) in Proteus Syndrome

MK-7075 (Miransertib) in Proteus Syndrome

Condition
Proteus Syndrome
Intervention / Treatment

-

Contacts and Locations

Bethesda

National Institutes of Health Clinical Center, Bethesda, Maryland, United States, 20892

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility Criteria

  • * Signed informed consent, and when applicable, signed assent
  • * Have a molecular diagnosis of Proteus syndrome with documented somatic AKT1 mutation from a CLIA-certified laboratory or international equivalent.
  • * Have progressive and measurable disease (e.g., a measurable manifestation of Proteus syndrome with evidence or report of worsening of manifestation(s)/ in the last 12 months)
  • * Adequate organ function as indicated by the following laboratory values:
  • * Hemoglobin (Hgb): \>=10.0 g/dL
  • * Glycated hemoglobin (HbA1c): \<=8% (\<=64 mmol/mol)
  • * Absolute neutrophil count (ANC): \>=1.5 x 10\^9/L
  • * Platelet count \>=150 x 10\^9/L
  • 1. Total bilirubin \<=2 x upper limit of normal (ULN)
  • 2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<=3 x ULN
  • 1. Serum creatinine depending on age:
  • * Cholesterol: \<=400 mg/dL (\<=10.34 mmol/L)
  • * Triglyceride: \<=500 mg/dL (\<=5.7 mmol/L)
  • * If a female is of child-bearing potential, documentation of a negative pregnancy test is required prior to enrollment. Sexually active participants (male and female) must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse while on study and for up to 90 days after ending treatment
  • * Ability to complete the questionnaires by the participant and/or his/her caregiver
  • * Individuals without an evaluable plantar CCTN
  • * No prior exposure to miransertib
  • * Male or female participants age \>=3 years old and BSA of \>=0.33 m\^2
  • * Any experimental systemic therapy for the purpose of treating Proteus syndrome (e.g., sirolimus, everolimus, high dose steroids, alpelisib) within two weeks of the first dose of miransertib, except for participants who were previously or are currently treated with miransertib under a Compassionate Use/Expanded Access program or existing protocol
  • * Participants who were previously treated with or currently are receiving miransertib will be enrolled on Cohort 3 and treated according to the Schedule of Assessments/Study Visits defined in this protocol
  • * Intolerance of, or severe toxicity attributed to, AKT inhibitors (e.g., miransertib, uprosertib, afuresertib, ipatasertib)
  • * Concurrent severe uncontrolled illness not related to Proteus syndrome
  • * Ongoing or active infection
  • * Known human immunodeficiency virus (HIV) infection malabsorption syndrome
  • * Psychiatric illness/substance abuse/social situation that would limit compliance with study requirements
  • * Pregnant or breastfeeding (contraception requirements can be found above and in the informed consent form)
  • * Inability to comply with study evaluations or to follow drug administration guidelines
  • * Concomitant use of a prohibited medication
  • * Regular tobacco use and/or use of cannabidiol/tetrahydrocannabidiol (CBD/THC), and/or vaping products

Ages Eligible for Study

3 Years to 99 Years

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

No

Collaborators and Investigators

National Human Genome Research Institute (NHGRI),

Leslie G Biesecker, M.D., PRINCIPAL_INVESTIGATOR, National Human Genome Research Institute (NHGRI)

Study Record Dates

2028-03-31