An Exploratory Study to Evaluate the Efficacy and Safety of FCN-159 in Patients With Brain Arteriovenous Malformations

NCT06913725 | Recruiting Phase 2

• 1 other identifier: hongtao
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

A single-center, open-label, non-randomized controlled exploratory study is conducted in the Xuanwu Hospital Capital Medical University to evaluate the efficacy and safety of FCN-159 in patients with brain arteriovenous malformations (BAVM), aiming to overcome the current clinical challenges caused by the lack of available drugs for this disease.

Conditions

Brain Arteriovenous Malformations

Keywords

Brain Arteriovenous Malformation; MEK Inhibitors; Pharmacological Treatment

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR) assessed by Silence-MRA

  1 year

Secondary Outcomes (15)

• DSA-assessed ORR (Objective Response Rate).

  1 year

• Changes in lesion volume at 3 months on Silence-MRA

  3 months

• Changes in lesion volume at 6 months on Silence-MRA

  6 months

• Changes in lesion volume at 12 months on Silence-MRA

  12 months

• Changes in lesion volume at 12 months assessed by DSA

  12 months

Other Outcomes (2)

• Maximum Plasma Concentration [Cmax]

  3 months, 6 months, 12 months

• Area under the plasma concentration versus time curve (AUC)

  3 months, 6 months, 12months

Study Arms (2)

Open label FCN-159

EXPERIMENTAL

Participants receive 8mg FCN-159 orally once daily. Participants continue to reveive FCN-159 until disease progression, unacceptable toxicity or other end-of-treatment criteria.

Drug: FCN-159

No-treatment control

NO INTERVENTION

Patients in the control group will undergo conservative observation throughout the study period.

Interventions

FCN-159 DRUG

An investigational oral MEK inhibitor

Open label FCN-159

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age ≥ 18 years and ≤ 60 years.
• Diagnosis of brain arteriovenous malformation (AVM) confirmed by DSA.
• Spetzler-Martin grade IV-V
• No history of rupture of the AVM vessels.
• No aneurysmal structures that are amenable to interventional embolization.
• No major surgery within the past 3 months.
• Able to swallow and retain oral medication, with no significant gastrointestinal abnormalities that could affect drug absorption, such as malabsorption syndrome, bowel obstruction, or extensive gastrointestinal resection.
• Karnofsky Performance Score ≥ 50%
• The patient must have adequate organ and bone marrow function, and must not have received blood transfusions or used any supportive medications (such as cytokines or erythropoietin) to elevate white blood cells, platelets, or hemoglobin levels within 7 days prior to screening:
• Absolute neutrophil count ≥ 1.0 × 10\^9/L. Hemoglobin ≥ 90 g/L. Platelet count ≥ 100 × 10\^9/L. Total serum bilirubin ≤ 1.5 × upper limit of normal (ULN), patients with Gilbert's syndrome may have ≤ 3.0 × ULN.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.
• Albumin ≥ 3 g/dL. Creatinine \< 1.5 × ULN or creatinine clearance ≥ 50 mL/min. Urine protein \< 2+; if urine protein ≥ 2+, then 24-hour urine protein quantification must be ≤ 1g.
• Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
• The patient must voluntarily sign a written informed consent and be able to complete follow-up visits.
• For patients of reproductive potential: the patient must agree to use an effective contraceptive method, such as combined hormonal contraception, progestin-only contraception with ovulation suppression, intrauterine device (IUD), intrauterine system (IUS), bilateral tubal ligation, partner's vasectomy, or complete abstinence during the treatment period and for at least 90 days after the last dose of study treatment. Male patients should agree to avoid sperm donation for at least 90 days after the last dose of treatment.

You may not qualify if:

• Patients with multiple arteriovenous malformation lesions (excluding segmental lesions such as CAMS syndrome) or extracranial arteriovenous malformation lesions;
• Diagnosed with Hereditary Hemorrhagic Telangiectasia (HHT), Capillary Malformation-Arteriovenous Malformation syndrome (CM-AVM), PTEN Hamartoma Tumor Syndrome (PHTS), or CLOVES syndrome;
• Patients who have received one of the following treatments after birth: a. Stereotactic radiation therapy, surgical treatment, or interventional embolization for BAVM; b. Pharmacological treatment for BAVM; c. Participation in other interventional clinical trials for BAVM;
• History of ruptured bleeding from malformed vascular clusters or other causes of brain hemorrhage, including subarachnoid hemorrhage, before the screening period;
• Patients with malignant tumors currently or within the past three years, except for non-melanoma skin basal cell carcinoma, in situ breast cancer, or in situ cervical cancer;
• Unable to undergo MRI scans and/or have contraindications to MRI (e.g., interference with MRI target lesion volume analysis due to prosthetics, braces, etc.);
• Unable to undergo DSA and/or have contraindications to DSA (e.g., contrast agent allergy, coagulopathy, etc.);
• Poorly controlled epilepsy;
• Uncontrolled, unstable hypertension: Repeated measurements showing systolic blood pressure \>140 mmHg or diastolic blood pressure \>90 mmHg with antihypertensive treatment;
• Dysphagia, active gastrointestinal diseases, malabsorption syndrome, or other conditions affecting the absorption of study drugs;
• Piror or current retinal vein occlusion (RVO), retinal pigment epithelium detachment (RPED), glaucoma, or other significant abnormalities in ophthalmologic examinations;
• Interstitial lung disease, including clinically significant radiation pneumonitis;
• Cardiac function or comorbidities that meet one of the following conditions: a. Three 12-lead ECG measurements conducted during the screening period at the study center, with an average QTcF \>470 ms calculated using the QTcF formula for the instruments employed; presence of risk factors for QTcF prolongation, such as uncorrectable hypokalemia, inherited long QT syndrome, or taking drugs known to prolong QTcF (mainly Class Ia, Ic, III antiarrhythmic drugs). New York Heart Association (NYHA) functional classification ≥3 congestive heart failure; c. Clinically significant arrhythmias, including but not limited to complete left bundle branch block; d. Documented, clinically significant coronary artery disease, cardiomyopathy, or severe valvular heart disease; e. Echocardiogram showing left ventricular ejection fraction (LVEF) \<50%; f. Bradycardia with a heart rate \<50 beats per minute;
• Family history of sudden cardiac death before the age of 50 in a first-degree relative;
• Active bacterial, fungal, or viral infections, including active hepatitis B (positive hepatitis B surface antigen and hepatitis B virus DNA \>1000 IU/ml, or meeting the study center's criteria for active hepatitis B infection), hepatitis C (positive hepatitis C virus RNA), or HIV infection (HIV positive);

Sponsors & Collaborators

• Xuanwu Hospital, Beijing: lead
• Shanghai Fosun Pharmaceutical Industry Development Co., Ltd: collaborator

Study Sites (1)

the Department of Neurosurgery, China International Neuroscience Institute, Xuanwu Hospital, Capital Medical University

Beijing, Beijing Municipality, No. 45, Changchun Street, China

RECRUITING

Central Study Contacts

Tao Hong, MD

CONTACT

+86-13810000653; hongtao.edu@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The experimental group will receive the medication. In this study, the patients in the experimental group will be matched 1:1 with control group patients based on factors such as gender, age (±5 years), the anatomical location of the BAVM lesion, and the Spetzler-Martin grade. Patients in the control group will receive no treatment during the study period.

Study Record Dates

• First Submitted: March 18, 2025
• First Posted: April 6, 2025
• Study Start: February 24, 2025
• Primary Completion: March 31, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: April 6, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Available from 6 months following analysis and article publication
• Access Criteria: Future researchers must be from a recognised research institution whose proposed use of the data has been ethically reviewed and approved by an independent committee and who accept Department of Neurosurgery, Xuanwu Hospital, Capital Medical University's conditions for access

Locations

CN (1)