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: The 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. ...
Name: Miransertib (ARQ092)
Description: Change in relative lesional size from baseline will be used to classify each subject as either a responder or nonresponder (binary) in the treated population. The primary endpoint is response rate (defined as ( 5% relative increase from baseline) in the CCTN lesional area relative to the total plantar area as assessed by blinded central photography review.
Measure: CCTN Time: baseline, one yearDescription: Duration of response is defined as the amount of time from first response signal to annual progression of CCTN relative to sole greater than 5% or EOT.
Measure: Duration of Response Time: Periodically throughout the studyDescription: Periodic safety (e.g., physical examination, vital sign measurements, clinical laboratory tests, use of concomitant medications and collection of AE information) assessments.
Measure: Long-term safety and tolerability Time: Periodically throughout the studyDescription: Change from baseline in pain score (Wong-Baker FACES scale), physical functioning (PROMIS), and quality of life (PedsQL)
Measure: Quality of life Time: Periodically throughout the studyAllocation: N/A
Single Group Assignment
There is one SNP
- Major surgery, radiotherapy, or immunotherapy within four weeks of the first dose of miransertib - 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 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 Proteus Syndrome Proteus Infections Proteus Syndrome Syndrome Proteus syndrome is a rare mosaic overgrowth disorder caused by a somatic gain of function variant, c. 49G>A, p.(Glu17Lys) in the oncogene AKT1, encoding the AKT1 kinase. --- Glu17Lys ---