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

• ClinicalTrials.gov Identifier: NCT05913037
• Recruitment Status: Recruiting
• First Posted: June 22, 2023
• Last Update Posted: March 15, 2024
• Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
• Information provided by (Responsible Party): Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.

Tracking Information

• First Submitted Date: June 6, 2023
• First Posted Date: June 22, 2023
• Last Update Posted Date: March 15, 2024
• Actual Study Start Date: June 20, 2023
• Estimated Primary Completion Date: June 30, 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 16, 2023)

Objective response rate (ORR) evaluated by BIRC (Response evaluation in Nerufibromatosis and Schwannomatosis, REiNS criteria) [ Time Frame: Through study completion, an average of 2 years ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 16, 2023)

• Objective response rate (ORR) evaluated by the investigator (REiNS criteria) [ Time Frame: Through study completion, an average of 2 years ]
  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.
• Duration of response (DOR) evaluated by BIRC and the investigator; [ Time Frame: Through study completion, an average of 2 years ]
  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.
• Disease control rate (DCR) evaluated by BIRC and the investigator; [ Time Frame: Through study completion, an average of 2 years ]
  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.
• Clinical benefit rate (CBR)evaluated by BIRC and the investigator; [ Time Frame: Through study completion, an average of 2 years ]
  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.
• Progression free survival (PFS) evaluated by BIRC and the investigator; [ Time Frame: Through study completion, an average of 2 years ]
  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.
• Time to progression (TTP) evaluated by BIRC and the investigator; [ Time Frame: Through study completion, an average of 2 years ]
  TTP is defined as the time from randomization until date of disease progression by BIRC and investigator per REiNS criteria.
• Time to response (TTR) evaluated by BIRC and the investigator; [ Time Frame: Through study completion, an average of 2 years ]
  TTR is defined as the time from date of randomization until the date of objective response by BIRC and investigator per REiNS criteria.
• Change from baseline in pain intensity score [ Time Frame: Through study completion, an average of 2 years ]
  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.
• Change from baseline in appearance [ Time Frame: Through study completion, an average of 2 years ]
  Change in appearance from baseline for Arm A versus Arm B as assessed using a sponsor-customized 'appearance evaluation'PRO questionnaire, which is descriptive.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: FCN-159 in Adult Patients With Symptomatic, Inoperable Neurofibromatosis Type 1-Related Plexiform Neurofibromas
• Official Title: 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
• Brief Summary: A study to evaluate the efficacy of FCN-159 in adult patients with symptomatic, inoperable neurofibromatosis type 1-related plexiform neurofibromas.
• Detailed Description: 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Neurofibromatosis 1
• Plexiform Neurofibroma
• NF1

Intervention

• Drug: Test group (Group A): FCN-159 8 mg, orally, once daily;
  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.
• Drug: Control group (Group B): Placebo, orally, once daily;
  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.

Study Arms

• Experimental: FCN-159
  Experimental: FCN-159 Dosage form:tablet Specification: 1mg，4mg Dose: FCN-159 8 mg, orally, once daily Method of administration: Oral
  Intervention: Drug: Test group (Group A): FCN-159 8 mg, orally, once daily;
• Placebo Comparator: placebo
  Experimental: placebo Dosage form:tablet Specification: 1mg，4mg Dose: placebo 8 mg, orally, once daily Method of administration: Oral
  Intervention: Drug: Control group (Group B): Placebo, orally, once daily;

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 16, 2023): 162
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2026
• Estimated Primary Completion Date: June 30, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. ≥ 18 years old and ≤ 70 years old.
2. Patients must be diagnosed with symptomatic NF1-related plexiform neurofibromas (PNs) and require systemic therapy at the investigator's discretion.
3. Presence of measurable lesions, defined as ≥ 3 cm in length in at least one dimension, which can be evaluated for efficacy by MRI.
4. Karnofsky performance status score ≥ 70.
5. Patients with adequate organ and bone marrow functions.

Exclusion Criteria:

1. NF1-related malignancies requiring chemotherapy, radiotherapy, or surgery, such as medium to high grade optic glioma or malignant peripheral nerve sheath tumor.
2. 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).
3. Patients who cannot undergo MRI and/or have contraindications to MRI.
4. Patients with previous or current retinal vein obstruction (RVO), retinal pigment epithelial detachment (RPED), glaucoma, and other abnormal ophthalmic examination with clinical significance.
5. Interstitial pneumonia, including clinically significant radiation pneumonia.

6. Cardiac function or combined diseases meet one of the following conditions:

   1. QTcF value of > 470 milliseconds; patients with risk factors for QTcF prolongation or patients receiving drugs that prolong the QTcF interval.
   2. Congestive heart failure per New York Heart Association (NYHA) classification ≥ Class 3.
   3. Arrhythmias with clinical significance.
   4. Known concurrent clinically significant coronary artery disease, cardiomyopathy, and severe valvular disease.
   5. LVEF < 50%.
   6. Patients with a heart rate of < 50 beats/min.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Wenbin Li, MD; 15301377998; Neure55@126.com

• Listed Location Countries: China

Administrative Information

• NCT Number: NCT05913037
• Other Study ID Numbers: FCN-159-007
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Wenbin Li, MD; Beijing Tiantan Hospital

• PRS Account: Shanghai Fosun Pharmaceutical Industrial Development Co. Ltd.
• Verification Date: March 2024