* Miransertib Extension Study for PROS / PS Patients
Research type
Research Study
Full title
A Multicenter, Open-label, Phase 2, Extension Trial to Study the Long-term Safety in Participants With PROS or Proteus Syndrome Who Are Currently Being Treated with Miransertib in Other Studies
IRAS ID
300911
Contact name
Piers Nicholas (Nick) Plowman
Contact email
Sponsor organisation
Merck Sharp & Dohme LLC
Eudract number
2021-001369-19
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 11 months, 25 days
Research summary
Proteus syndrome (PS) is a rare condition characterised by overgrowth of the bones, skin, and other tissues. Organs and tissues affected by the disease grow out of proportion to the rest of the body. PS is caused by a mutation of the AKT1 (v-Akt murine thymoma viral oncogene homolog) gene. The AKT1 gene makes cells grow, develop, live, and die. A mutation in the AKT1 gene disrupts a cell's ability to control its own growth, allowing the cell to grow and divide abnormally. Increased cell division in various tissues and organs results in the abnormal growth features of PS.
Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum (PROS) is a group of rare disorders that cause overgrowth of parts of the body, due to mutations in the PIK3CA gene. The PIK3CA gene instructs cells in the body to make the phosphoinositide 3-kinase (PI3K) protein. The PI3K protein makes sure cells grow, develop, live, and die in the right way. However, in PROS, the PIK3CA gene mutates and consequently, the instructions the gene gives for making the PI3K protein are damaged. The PI3K protein does not work the way it should, causing cells to grow and divide abnormally, resulting in the features of PROS.
Onset of PS and PROS usually occurs at birth or in the first 6 to 18 months of life. Affected areas generally keep growing throughout the patient’s life, but at a slower pace after the patient reaches 30 years of age.
Currently there is no drug therapy for PS or PROS; the treatment consists of symptom management, mainly surgical management of overgrowth lesions, that ultimately leads to severe physical disabilities with unsatisfactory quality of life.
Miransertib is a novel, potent, and selective AKT inhibitor with activity against both the active and inactive forms of AKT.
This study is an extension study to Study MK-7075-002 and the ArQuleEAP. This study will evaluate the safety and tolerability of miransertib administered as monotherapy. The Sponsor estimates that the study will last approximately for 4 years and will recruit approximately 60 male and female participants who are actively being treated with miransertib as part of Study MK-7075-002 or ArQule’s EAP.
The study is sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (“MSD”), and will take place at 2 study centres in the UK.
REC name
East of England - Essex Research Ethics Committee
REC reference
22/EE/0198
Date of REC Opinion
13 Aug 2021
REC opinion
Favourable Opinion