MK-7075 (Miransertib) in Proteus Syndrome

NCT04316546 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 20003420-HG-0034
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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....

Conditions

Proteus Syndrome

Keywords

AKT1; CCTN; Mosaic Overgrowth Disorder

Outcome Measures

Primary Outcomes (1)

• CCTN

  Change in CCTN involvement of the plantar surface from baseline will be used to classify each subject as either a responder or non-responder (binary) in the treated population. The primary endpoint is response rate (defined as =\< 5% increase in plantar involvement from baseline over 26 cycles). This will be assessed by blinded central photography review.

  Baseline, two years

Secondary Outcomes (3)

• Quality of life

  Periodically throughout the study (described in schedule of activities)

• Long-term safety and tolerability

  Periodically throughout the study (described in schedule of activities)

• Duration of response

  Periodically throughout the study (described in schedule of activities)

Study Arms (1)

MK-7075 (miransertib)

EXPERIMENTAL

This is a single-arm study. All study participants will be taking the experimental drug, MK-7075 (miransertib).

Drug: MK-7075 (miransertib)

Interventions

MK-7075 (miransertib) DRUG

MK-7075 (miransertib) is a small molecule developed by ArQule Inc., a wholly owned subsidiary of Merck Sharp \&amp; Dohme (Merck), that effectively inhibits AKT. Proteus syndrome is caused by mosaic activating mutations in AKT1. This is a Phase 2 trial investigating the efficacy of miransertib as a treatment for adult and pediatric patients with Proteus syndrome.

MK-7075 (miransertib)

Eligibility Criteria

• Age: 3 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants in all Cohorts must meet the criteria below:
• 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:
• Hematological:
• 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
• Hepatic:
• Total bilirubin \<=2 x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \<=3 x ULN
• Renal:
• Serum creatinine depending on age:

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• \- History of Type 1 or Type 2 uncontrolled diabetes mellitus requiring regular medication (other than metformin or other oral hypoglycemic agents) or fasting glucose greater than or equal to 160 mg/dL ( if \>12 years old) and greater than or equal to 180 mg/dL (if less than or equal to 12 years old) at the baseline/screening visit
• History of clinically significant cardiac disorders:
• Myocardial infarction (MI) or congestive heart failure defined as Class II-IV per the New York Heart Association (NYHA) classification within six months of the first dose of miransertib (MI occurring \>6 months of the first dose of miransertib will be permitted)
• Grade 2 (per National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE v 5.0\]) or worse conduction defect (e.g., right or left bundle branch block).
• Major surgery, radiotherapy, chemotherapy, 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 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

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (3)

• Lindhurst MJ, Yourick MR, Yu Y, Savage RE, Ferrari D, Biesecker LG. Repression of AKT signaling by ARQ 092 in cells and tissues from patients with Proteus syndrome. Sci Rep. 2015 Dec 11;5:17162. doi: 10.1038/srep17162.

  PMID: 26657992 BACKGROUND

• Keppler-Noreuil KM, Sapp JC, Lindhurst MJ, Darling TN, Burton-Akright J, Bagheri M, Dombi E, Gruber A, Jarosinski PF, Martin S, Nathan N, Paul SM, Savage RE, Wolters PL, Schwartz B, Widemann BC, Biesecker LG. Pharmacodynamic Study of Miransertib in Individuals with Proteus Syndrome. Am J Hum Genet. 2019 Mar 7;104(3):484-491. doi: 10.1016/j.ajhg.2019.01.015. Epub 2019 Feb 22.

  PMID: 30803705 BACKGROUND

• Nathan NR, Patel R, Crenshaw MM, Lindhurst MJ, Olsen C, Biesecker LG, Keppler-Noreuil KM, Darling TN. Pathogenetic insights from quantification of the cerebriform connective tissue nevus in Proteus syndrome. J Am Acad Dermatol. 2018 Apr;78(4):725-732. doi: 10.1016/j.jaad.2017.10.018. Epub 2017 Oct 16.

  PMID: 29042227 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Proteus Syndrome

Interventions

Miransertib

Condition Hierarchy (Ancestors)

Hamartoma Syndrome, Multiple; Hamartoma; Neoplasms; Neoplasms, Multiple Primary; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Limb Deformities, Congenital; Musculoskeletal Abnormalities; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Leslie G Biesecker, M.D.

  National Human Genome Research Institute (NHGRI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christopher A Ours, M.D.

CONTACT

(301) 443-8750; chris.ours@nih.gov

Leslie G Biesecker, M.D.

CONTACT

(301) 402-2041; lesb@mail.nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2020
• First Posted: March 20, 2020
• Study Start: May 20, 2022
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2028
• Last Updated: May 1, 2026

Record last verified: 2026-04-15

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)