Proteus SyndromePhase 2NCT04316546
MK-7075 (Miransertib) in Proteus Syndrome
A Phase 2 study testing MK-7075 (miransertib) in people with Proteus Syndrome, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 3 to 99 years
- Conditions the study is for
- Proteus Syndrome
- What is being tested?
- MK-7075 (miransertib)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- 20 May 2022to 1 Jul 2028
- Phase
- Phase 2
- 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 3 to 99 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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:
Show all 36Show fewer
- 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:
- 2-5 years male and female: <=0.50 mg/dL
- 6-10 years male and female: <=0.59 mg/dL
- 11-15 years male and female: <=1.2 mg/dL
- >15 years male and female: <=1.5 mg/dL
- Metabolic (lipids):
- 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
- The following specific criteria will be used to assign participants to Cohorts:
- Cohort 1 (Proteus syndrome with plantar CCTN) specific criteria:
- Have at least one plantar CCTN that can accurately be measured by standardized photography. The CCTN is defined as a nevus with at least two gyri and three sulci affecting 10% - 70% of the total surface area of the foot.
- Male or female participants age >=3 and <=17 years old and BSA of >=0.33 m^2
- Cohort 2 (Proteus syndrome without plantar CCTN) specific criteria:
- 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
- Cohort 3 (Proteus syndrome previously treated with miransertib) specific criteria:
- Participants previously treated with miransertib or currently receiving miransertib under Compassionate Use/Expanded Access or an existing trial (i.e., 16-HG-0014)
- Male or female participants >=3 years old and BSA of >=0.33 m^2
- Note: All participants must meet Cohort-related age criteria by/on the date of the first dose, Cycle 1 Day 1
Who cannot join
- 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 >=160 mg/dL ( if >12 years old) and >=180 mg/dL (if <=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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: A Multi-Cohort Phase 2 Dose-Escalation Study of MK-7075 (Miransertib) in Proteus Syndrome
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.
Read more
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 with possibility of continued treatment beyond 4 years....
Read the detailed description
Study Description: The primary objective of this study is to determine the response rate of miransertib as measured by the change in cerebriform connective tissue nevus (CCTN) involvement of the plantar surface from baseline, using blinded independent central review of lesional photography in individuals with Proteus syndrome (Cohort 1). Cohorts 2 and 3 will enroll additional patients whose non-plantar CCTN Proteus syndrome-associated lesions will be evaluated to address the secondary and exploratory study objectives. All participants will be treated with miransertib in continuous, 28-day cycles. Participants in Cohorts 1 and 2 will receive miransertib at the starting dose of 15 mg/m^2 daily for the first three cycles, and then the dose will be increased to 25 mg/m^2 daily, provided no clinically significant drug-related toxicity is observed. Participants in Cohort 3 will receive miransertib at the dose they were on at the time of enrollment if continuing use of miransertib or at the starting dose for Cohorts 1 and 2, not to exceed 45 mg/dose daily. Safety and toxicity data will be gathered on all participants. Participants will initially be on treatment for up to 52 cycles, after which they may be eligible for continued treatment. The final clinical safety follow-up will be performed 30 days after the last dose.
Objectives:
Primary Objective: To determine the response to treatment with miransertib as measured by the growth of plantar CCTN in individuals with Proteus syndrome.
Secondary Objectives:
- To estimate the change from baseline in pain in participants treated with miransertib
- To estimate change from baseline in physical functioning in participants treated with miransertib
- To estimate change from baseline in quality of life in participants treated with miransertib
- To describe the long-term tolerability and safety of miransertib
- To determine the duration of response in responders with respect to the primary study endpoint
Exploratory Objectives:
- To describe the effect of miransertib on Proteus syndrome-related overgrowth manifestations.
- To describe the effect of miransertib on the rate of growth of the CCTN lesion as compared to historical data from untreated participants
- To determine if the clinical gestalt status of participants with Proteus syndrome improves on/after treatment with miransertib
- To describe the effect of miransertib on D-dimer and fibrinogen levels
- To describe the PK profile of miransertib
Endpoints:
Primary Endpoint (assessed in Cohort 1):
Change in lesion proportion of the plantar surface will be used to classify each participant as either a responder or non-responder (binary) in the treated population. The primary endpoint is the response rate (defined as a <= 5% increase in the proportion of plantar involvement from baseline after 26 cycles) as assessed by blinded central photography review.
Secondary Endpoints:
- Change from baseline in pain score as assessed by the NRS-11 Pain Rating Scale
- Change from baseline in physical functioning as assessed by PROMIS(R) (Pediatric Upper Extremity Short Form 8a, Parent Proxy Upper Extremity Short Form 8a, Pediatric Mobility Short Form 8a, Parent Proxy Mobility Short Form 8a, Physical Function Short Form 8b, Parent Proxy Pain Behavior Short Form 8a)
- Change from baseline in quality of life as assessed by the Pediatric Quality of Life Inventory (PedsQL)
- Safety and tolerability as assessed by frequency, duration and severity of AEs from the first dose of miransertib through 30 days after the last dose of the drug (severity of AEs will be assessed by CTCAE version 5.0)
- Time from response to failure to respond defined as having a > 5% increase in the proportion of plantar involvement over a 26 cycle period assessed every 6-7 cycles
Exploratory Endpoints:
- Change from baseline in selected disease-related manifestations, such as those evaluated by imaging (e.g., x-ray, CT, MRI, ultrasound, photography) and/or physical function assessments (e.g., pulmonary function test, six-minute walk test, pegboard test)
- Behavior of the CCTN lesion while on continuous treatment with miransertib using historical control data for comparison
- Change in clinical gestalt status in treated participants using a blinded review panel
- Change from baseline in D-dimer and fibrinogen levels
- PK parameters (e.g., maximum plasma drug concentration [Cmax], time to maximum plasma drug concentration [Tmax], and area under the curve [AUC]) which are calculated from plasma concentration-time data
- Conditions
- Proteus Syndrome
- Being tested
- MK-7075 (miransertib)
- Keywords
- AKT1, CCTN, Mosaic Overgrowth Disorder
- Medical subject headings
- Proteus Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MK-7075 (miransertib)Drug
MK-7075 (miransertib) is a small molecule developed by ArQule Inc., a wholly owned subsidiary of Merck Sharp \& 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.
| Study group | Role | What they receive |
|---|---|---|
| MK-7075 (miransertib) | Experimental | This is a single-arm study. All study participants will be taking the experimental drug, MK-7075 (miransertib). Receives: Drug: MK-7075 (miransertib) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, two years
Secondary outcomes (3)
Quality of life
Change from baseline in pain score (NRS-11), physical functioning (PROMIS), and quality of life (PedsQL).
Measured: Periodically throughout the study (described in schedule of activities)
Long-term safety and tolerability
Periodic safety (e.g., physical examination, vital sign measurements, clinical laboratory tests, use of concomitant medications and collection of AE information) assessments.
Measured: Periodically throughout the study (described in schedule of activities)
Duration of response
Duration of response is defined as the amount of time from first response signal to progression of CCTN involvement >5% over a 26 cycle period assessed every 6-7 cycles
Measured: Periodically throughout the study (described in schedule of activities)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Mar 2020
- Study start20 May 2022
- Primary completion25 Jun 2026
- Study completion1 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Proteus SyndromeStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Leslie G Biesecker, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04316546
- Sponsor's protocol ID
- 200034
- Other IDs
- 20-HG-0034
- Status last verified
- 13 Jul 2026
- First submitted
- 19 Mar 2020
- Last updated
- 17 Jul 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 26657992Keppler-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.
PubMed 30803705Nathan 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.
PubMed 29042227Khan RMN, Arisa OT, Zeng Y, Rostagni O, Redick C, Paris KM, Biesecker LG, Ours CA, Figg WD. Development and validation of an LC-MS/MS assay for the quantification of Miransertib in human plasma and clinical application. J Chromatogr B Analyt Technol Biomed Life Sci. 2026 Sep 1;1281:125161. doi: 10.1016/j.jchromb.2026.125161. Epub 2026 May 29.
PubMed 42224880
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Cohort Phase 2 Dose-Escalation Study of MK-7075 (Miransertib) in Proteus Syndrome
- ClinicalTrials.gov ID
- NCT04316546
- Acronym / sponsor ID
- 200034
- Conditions
- Proteus Syndrome
- Keywords
- AKT1, CCTN, Mosaic Overgrowth Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 38 participants (actual)
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- 20 May 2022 (actual)
- Primary completion
- 25 Jun 2026 (actual)
- Study completion
- 1 Jul 2028 (estimated)
- First posted
- 20 Mar 2020 (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.
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 with possibility of continued treatment beyond 4 years....
Detailed description
Study Description: The primary objective of this study is to determine the response rate of miransertib as measured by the change in cerebriform connective tissue nevus (CCTN) involvement of the plantar surface from baseline, using blinded independent central review of lesional photography in individuals with Proteus syndrome (Cohort 1). Cohorts 2 and 3 will enroll additional patients whose non-plantar CCTN Proteus syndrome-associated lesions will be evaluated to address the secondary and exploratory study objectives. All participants will be treated with miransertib in continuous, 28-day cycles. Participants in Cohorts 1 and 2 will receive miransertib at the starting dose of 15 mg/m^2 daily for the first three cycles, and then the dose will be increased to 25 mg/m^2 daily, provided no clinically significant drug-related toxicity is observed. Participants in Cohort 3 will receive miransertib at the dose they were on at the time of enrollment if continuing use of miransertib or at the starting dose for Cohorts 1 and 2, not to exceed 45 mg/dose daily. Safety and toxicity data will be gathered on all participants. Participants will initially be on treatment for up to 52 cycles, after which they may be eligible for continued treatment. The final clinical safety follow-up will be performed 30 days after the last dose.
Objectives:
Primary Objective: To determine the response to treatment with miransertib as measured by the growth of plantar CCTN in individuals with Proteus syndrome.
Secondary Objectives:
- To estimate the change from baseline in pain in participants treated with miransertib
- To estimate change from baseline in physical functioning in participants treated with miransertib
- To estimate change from baseline in quality of life in participants treated with miransertib
- To describe the long-term tolerability and safety of miransertib
- To determine the duration of response in responders with respect to the primary study endpoint
Exploratory Objectives:
- To describe the effect of miransertib on Proteus syndrome-related overgrowth manifestations.
- To describe the effect of miransertib on the rate of growth of the CCTN lesion as compared to historical data from untreated participants
- To determine if the clinical gestalt status of participants with Proteus syndrome improves on/after treatment with miransertib
- To describe the effect of miransertib on D-dimer and fibrinogen levels
- To describe the PK profile of miransertib
Endpoints:
Primary Endpoint (assessed in Cohort 1):
Change in lesion proportion of the plantar surface will be used to classify each participant as either a responder or non-responder (binary) in the treated population. The primary endpoint is the response rate (defined as a <= 5% increase in the proportion of plantar involvement from baseline after 26 cycles) as assessed by blinded central photography review.
Secondary Endpoints:
- Change from baseline in pain score as assessed by the NRS-11 Pain Rating Scale
- Change from baseline in physical functioning as assessed by PROMIS(R) (Pediatric Upper Extremity Short Form 8a, Parent Proxy Upper Extremity Short Form 8a, Pediatric Mobility Short Form 8a, Parent Proxy Mobility Short Form 8a, Physical Function Short Form 8b, Parent Proxy Pain Behavior Short Form 8a)
- Change from baseline in quality of life as assessed by the Pediatric Quality of Life Inventory (PedsQL)
- Safety and tolerability as assessed by frequency, duration and severity of AEs from the first dose of miransertib through 30 days after the last dose of the drug (severity of AEs will be assessed by CTCAE version 5.0)
- Time from response to failure to respond defined as having a > 5% increase in the proportion of plantar involvement over a 26 cycle period assessed every 6-7 cycles
Exploratory Endpoints:
- Change from baseline in selected disease-related manifestations, such as those evaluated by imaging (e.g., x-ray, CT, MRI, ultrasound, photography) and/or physical function assessments (e.g., pulmonary function test, six-minute walk test, pegboard test)
- Behavior of the CCTN lesion while on continuous treatment with miransertib using historical control data for comparison
- Change in clinical gestalt status in treated participants using a blinded review panel
- Change from baseline in D-dimer and fibrinogen levels
- PK parameters (e.g., maximum plasma drug concentration [Cmax], time to maximum plasma drug concentration [Tmax], and area under the curve [AUC]) which are calculated from plasma concentration-time data
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MK-7075 (miransertib) | Experimental | Drug: MK-7075 (miransertib)This is a single-arm study. All study participants will be taking the experimental drug, MK-7075 (miransertib). |
Who may qualify
- Ages
- 3 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (36 listed)
- 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:
- 2-5 years male and female: <=0.50 mg/dL
Key exclusion criteria (17 listed)
- 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 >=160 mg/dL ( if >12 years old) and >=180 mg/dL (if <=12 years old) at the baseline/screening visit
- History of clinically significant cardiac disorders:
- 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
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 |
|---|---|---|
| MK-7075 (miransertib)MK-7075 (miransertib) is a small molecule developed by ArQule Inc., a wholly owned subsidiary of Merck Sharp \& 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. | Drug | MK-7075 (miransertib) |
Primary outcome
CCTN
Time frame: Baseline, two years
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.
3 secondary outcomes
Quality of life
Time frame: Periodically throughout the study (described in schedule of activities)
Long-term safety and tolerability
Time frame: Periodically throughout the study (described in schedule of activities)
Duration of response
Time frame: Periodically throughout the study (described in schedule of activities)
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 17 Jul 2026.
- Background: PubMed 26657992Lindhurst 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.
- Background: PubMed 30803705Keppler-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.
- Background: PubMed 29042227Nathan 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.
- Derived from this study: PubMed 42224880Khan RMN, Arisa OT, Zeng Y, Rostagni O, Redick C, Paris KM, Biesecker LG, Ours CA, Figg WD. Development and validation of an LC-MS/MS assay for the quantification of Miransertib in human plasma and clinical application. J Chromatogr B Analyt Technol Biomed Life Sci. 2026 Sep 1;1281:125161. doi: 10.1016/j.jchromb.2026.125161. Epub 2026 May 29.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Proteus Syndrome
RecruitingObservational study
Study of Proteus Syndrome and Related Congenital Disorders
Proteus Syndrome, PIK3CA Related Overgrowth Spectrum
Active, not recruitingPhase 2
A Study of the Safety and Tolerability in Participants With PIK3CA-related Overgrowth Spectrum or Proteus Syndrome Who Are Being Treated With Miransertib (MK-7075) in Other Studies (MK-7075-006)
PIK3CA-Related Overgrowth Spectrum (PROS)/Proteus Syndrome (PS)
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. This study is not recruiting at the moment.
Leslie G Biesecker, M.D. principal investigator
National Human Genome Research Institute (NHGRI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MK-7075 (miransertib) in people with Proteus Syndrome, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
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 36 inclusion and 17 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: under way, not looking for participants, as of the sponsor's last update on 17 Jul 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 States. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
CCTN (time frame: Baseline, two years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04316546, which also lists 4 linked publications.
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 17 Jul 2026.