Vascular malformation Trials in Disease

Study of RLY-2608 for Adults and Children with PIK3CA-Related Overgrowth and Malformations

This trial is investigating a new medication called RLY-2608 for people affected by PIK3CA-related overgrowth spectrum and malformations. This condition occurs due to a mutation in the PIK3CA gene, which leads to abnormal growth in various parts of the body, including bones, skin, and other tissues. The overgrowth can cause asymmetry, pain, mobility problems, and other functional difficulties depending on where it occurs.

Main inclusion criteria:

• Participants must have a clinical diagnosis of PIK3CA-related overgrowth spectrum or a vascular malformation as classified by international standards
• The presence of one or more documented PIK3CA mutations in affected tissue or in cell-free DNA from the lesion or blood
• Willingness to provide archived fluid or tissue samples from the affected area, or undergo a biopsy if safe and medically possible
• Adequate performance status, measured by age-appropriate scales that assess the ability to perform everyday activities
• Age between 2 and 17 years old
• Participants of any gender can take part

Main exclusion criteria:

• Any serious health condition that might interfere with the study
• Pregnancy or breastfeeding
• Participation in another clinical trial within the last 30 days
• Known allergy to the study medication or its ingredients
• History of certain types of cancer, unless in remission for a specified period
• Severe liver or kidney disease
• Uncontrolled high blood pressure
• History of heart attack or stroke within the last 6 months
• Current use of certain medications that might interfere with the study drug
• Inability to follow study procedures or instructions

Focus and goal of the trial:

The main purpose of this study is to determine the best dose of RLY-2608 for different age groups and to evaluate its safety and effectiveness. RLY-2608 is taken as a capsule and works by targeting and inhibiting a specific protein affected by the PIK3CA mutation. By blocking this protein's activity, the treatment may help manage symptoms and reduce abnormal growth.

The study is conducted in several phases. Initially, participants will receive RLY-2608 to identify the most suitable dose while monitoring for any side effects. In a later phase, the effectiveness of RLY-2608 will be compared to a placebo to assess how well it works in reducing the size of overgrowths or malformations. Throughout the study, participants will be regularly monitored through check-ups, assessments, and various tests to measure changes in lesion volume and overall response to treatment.

Investigational drug:

RLY-2608 is an experimental medication classified as a PI3Kα inhibitor. It is designed to selectively target the mutant form of the PI3Kα enzyme, which plays a role in cell growth and survival. By inhibiting this enzyme, RLY-2608 may help reduce abnormal cell growth and proliferation caused by PIK3CA mutations. The medication is administered orally in capsule form and is currently in the experimental phase, meaning it is not yet a standard treatment option. This trial aims to provide valuable information about whether RLY-2608 can become a viable treatment option for individuals with PIK3CA-related conditions in the future.