FCN-159 in Adult Patients With Symptomatic, Inoperable Neurofibromatosis Type 1-Related Plexiform Neurofibromas

Study Overview
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Brief Summary
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A study to evaluate the efficacy of FCN-159 in adult patients with symptomatic, inoperable neurofibromatosis type 1-related plexiform neurofibromas.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, multi-center phase III clinical study to evaluate the efficacy and safety of FCN-159 in adult patients with symptomatic, inoperable neurofibromatosis type 1-related plexiform neurofibromas.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Multi-center Phase III Clinical Study to Evaluate the Efficacy and Safety of FCN-159 in Adult Patients With Symptomatic, Inoperable Neurofibromatosis Type 1-Related Plexiform Neurofibromas

Conditions
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NF1, Neurofibromatosis 1, Plexiform Neurofibroma

Intervention / Treatment
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* Drug: Test group (Group A): FCN-159 8 mg, orally, once daily;
* Drug: Control group (Group B): Placebo, orally, once daily;


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years old and ≤ 70 years old. Patients must be diagnosed with symptomatic NF1-related plexiform neurofibromas (PNs) and require systemic therapy at the investigator's discretion. Presence of measurable lesions, defined as ≥ 3 cm in length in at least one dimension, which can be evaluated for efficacy by MRI. Karnofsky performance status score ≥ 70. Patients with adequate organ and bone marrow functions. Exclusion Criteria: NF1-related malignancies requiring chemotherapy, radiotherapy, or surgery, such as medium to high grade optic glioma or malignant peripheral nerve sheath tumor. Patients with a history of or concurrently with other malignancies (excluding cured non-melanoma skin basal cell carcinoma, breast cancer in situ or cervical cancer in situ, and other malignancies without evidence of disease within 5 years). Patients who cannot undergo MRI and/or have contraindications to MRI. Patients with previous or current retinal vein obstruction (RVO), retinal pigment epithelial detachment (RPED), glaucoma, and other abnormal ophthalmic examination with clinical significance. Interstitial pneumonia, including clinically significant radiation pneumonia. Cardiac function or combined diseases meet one of the following conditions: QTcF value of > 470 milliseconds; patients with risk factors for QTcF prolongation or patients receiving drugs that prolong the QTcF interval. Congestive heart failure per New York Heart Association (NYHA) classification ≥ Class 3. Arrhythmias with clinical significance. Known concurrent clinically significant coronary artery disease, cardiomyopathy, and severe valvular disease. LVEF < 50%. Patients with a heart rate of < 50 beats/min.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FCN-159<br>Experimental: FCN-159 Dosage form:tablet Specification: 1mg，4mg Dose: FCN-159 8 mg, orally, once daily Method of administration: Oral | Drug: Test group (Group A): FCN-159 8 mg, orally, once daily;<br>* After completing all screening visit items, qualified patients will be randomly assigned to the test group (Group A) or control group (Group B) in a 2:1 ratio, and receive FCN-159 or placebo within 3 days after randomization.<br>|
| Placebo Comparator: placebo<br>Experimental: placebo Dosage form:tablet Specification: 1mg，4mg Dose: placebo 8 mg, orally, once daily Method of administration: Oral | Drug: Control group (Group B): Placebo, orally, once daily;<br>* After completing all screening visit items, qualified patients will be randomly assigned to the test group (Group A) or control group (Group B) in a 2:1 ratio, and receive FCN-159 or placebo within 3 days after randomization.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) evaluated by BIRC (Response evaluation in Nerufibromatosis and Schwannomatosis, REiNS criteria) | ORR is defined as the proportion of patients who have a confirmed complete response or confirmed partial response as determined by ICR per REiNS criteria. | Through study completion, an average of 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) evaluated by the investigator (REiNS criteria) | ORR is defined as the proportion of patients who have a confirmed complete response or confirmed partial response as determined by ICR per REiNS criteria. | Through study completion, an average of 2 years | 
| Duration of response (DOR) evaluated by BIRC and the investigator; | DOR is defined as the time from the date of first documented response (which is subsequently confirmed) until progression by BIRC and the investigator per REiNS criteria or death due to any cause. | Through study completion, an average of 2 years | 
| Disease control rate (DCR) evaluated by BIRC and the investigator; | DCR is defined as the proportion of patients who have a confirmed complete response or confirmed partial response or stable disease as determined by BIRC and the investigator per REiNS criteria. | Through study completion, an average of 2 years | 
| Clinical benefit rate (CBR)evaluated by BIRC and the investigator; | CBR is defined as the proportion of patients who have a confirmed complete response or confirmed partial response or stable disease>48 weeks as determined by BIRC and the investigator per REiNS criteria. | Through study completion, an average of 2 years | 
| Progression free survival (PFS) evaluated by BIRC and the investigator; | PFS is defined as the time from randomization until date of disease progression by BIRC and investigator per REiNS criteria or death due to any cause. | Through study completion, an average of 2 years | 
| Time to progression (TTP) evaluated by BIRC and the investigator; | TTP is defined as the time from randomization until date of disease progression by BIRC and investigator per REiNS criteria. | Through study completion, an average of 2 years | 
| Time to response (TTR) evaluated by BIRC and the investigator; | TTR is defined as the time from date of randomization until the date of objective response by BIRC and investigator per REiNS criteria. | Through study completion, an average of 2 years | 
| Change from baseline in pain intensity score | Difference in mean change from baseline in overall tumor and target PN pain intensity score between Arm A and Arm B as assessed by the 11-point Numerical Rating Scale (NRS-11),which uses the range 0-10,higher scores mean worse outcome. | Through study completion, an average of 2 years | 
| Change from baseline in appearance | Change in appearance from baseline for Arm A versus Arm B as assessed using a sponsor-customized 'appearance evaluation'PRO questionnaire, which is descriptive. | Through study completion, an average of 2 years |