Clinical Study of CFH Protein Via Ice Microneedles for Radiation-Induced Skin Fibrosis

A Clinical Study to Evaluate the Safety and Tolerability of Intradermal Delivery of CFH Protein Via Ice Microneedles for the Prevention of Radiation-Induced Skin Fibrosis

This phase I, open-label, single-arm, non-randomized clinical trial uses a "3+3" dose-escalation design to evaluate the safety, tolerability, and preliminary efficacy of intradermal delivery of complement factor H (CFH) fragment (human, 860-1231aa) via ice microneedles for the prevention of radiation-induced skin fibrosis in patients with head and neck squamous cell carcinoma (excluding nasopharyngeal carcinoma) receiving postoperative adjuvant radiotherapy. The main questions are: 1. The safety profile, including dose-limiting toxicities (DLTs) within 28 days after the first dose, adverse events, and tolerability. 2.Preliminary efficacy, assessed by changes in irradiated skin thickness, palpation of fibrotic area, CTCAE grade ≤2 fibrosis rate, and quality of life. Participants receive CFH ice microneedle patches twice weekly for a total of 8 doses (starting at 0.5 mg, escalating to 1.0 mg and 2.0 mg), applied to the skin area to be irradiated.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma; Radiation-Induced Skin Fibrosis
• Intervention / Treatment: Biological: CFH Protein-loaded Ice Microneedles (0.5 mg); Biological: CFH Protein-loaded Ice Microneedles (1.0 mg); Biological: CFH Protein-loaded Ice Microneedles (2.0 mg)

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Xingchen Peng, MD, PhD; Phone Number: +8618980606753; Email: pxx2014@163.com

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Recruiting
      • West China Hospital, Sichuan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female patients aged 18 to 75 years (inclusive) at screening.
2. Histologically confirmed head and neck squamous cell carcinoma (excluding nasopharyngeal carcinoma) scheduled to receive postoperative adjuvant radiotherapy.
3. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.

4. Adequate major organ function within 7 days before treatment, meeting the following criteria:

   Hemoglobin ≥ 80 g/L; neutrophil count > 1.5 × 10⁹/L; platelet count ≥ 80 × 10⁹/L; Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT or AST ≤ 2.5 × ULN (or ≤ 5 × ULN in the presence of liver metastases); Serum creatinine ≤ 1.5 × ULN or creatinine clearance (CrCl) ≥ 60 mL/min (Cockcroft-Gault formula); Prothrombin time (PT) and international normalized ratio (INR) ≤ 1.5 × ULN (unless on warfarin anticoagulation); Left ventricular ejection fraction (LVEF) ≥ 50%.

5. Ability to understand and voluntarily sign a written informed consent form prior to any study procedures.

Exclusion Criteria:

1. Presence of ulceration or open wound in the treatment area, or any contraindication to cutaneous administration including: Inflammation, trauma, or skin breakdown at the administration site; Severe bleeding or coagulation tendency (e.g., markedly low platelet or clotting factors); Any abnormality or permanent body art (e.g., tattoo) at the administration site that would interfere with observation of local reactions;
2. Presence of connective tissue disease or other systemic dermatologic conditions (e.g., systemic lupus erythematosus, dermatomyositis, polymyositis, systemic sclerosis, scleroderma, toxic epidermal necrolysis, Stevens-Johnson syndrome, etc.).
3. Known allergy to the investigational drug (including any excipients) or history of severe allergic reactions to any drug, food, or vaccine, such as anaphylactic shock, laryngeal edema, anaphylactic dyspnea, Henoch-Schönlein purpura, thrombocytopenic purpura, or Arthus reaction.
4. Any uncontrolled clinical disease (e.g., respiratory, circulatory, digestive, nervous, hematologic, genitourinary, or endocrine system disease) or psychiatric disorder (e.g., depression, schizophrenia) that, in the investigator's judgment, would interfere with providing informed consent, interpretation of study results, pose additional risk to the patient, or otherwise compromise study objectives.
5. Participation in another clinical trial of a drug or device within 3 months prior to screening.
6. History of drug abuse or known medical, psychological, or social conditions (e.g., alcoholism or drug addiction).
7. Pregnant or breastfeeding women, or women/partners planning pregnancy during the period from screening through 12 months after the last dose.
8. Any other condition that, in the investigator's opinion, makes the patient unsuitable for participation in this trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Level 1: CFH Protein 0.5 mg via Ice Microneedles; Participants receive intradermal delivery of CFH protein at a total dose of 0.5 mg per administration via ice microneedle patches, twice weekly for a total of 8 doses, starting on the first day of radiotherapy.	Biological: CFH Protein-loaded Ice Microneedles (0.5 mg); Recombinant human CFH protein delivered intradermally via ice microneedle patches at a total dose of 0.5 mg per administration, twice weekly for a total of 8 doses, starting on the first day of radiotherapy.
Experimental: Dose Level 2: CFH Protein 1.0 mg via Ice Microneedles; Participants receive intradermal delivery of CFH protein at a total dose of 1.0 mg per administration via ice microneedle patches, twice weekly for a total of 8 doses, starting on the first day of radiotherapy.	Biological: CFH Protein-loaded Ice Microneedles (1.0 mg); Recombinant human CFH protein delivered intradermally via ice microneedle patches at a total dose of 1.0 mg per administration, twice weekly for a total of 8 doses, starting on the first day of radiotherapy.
Experimental: Dose Level 3: CFH Protein 2.0 mg via Ice Microneedles; Participants receive intradermal delivery of CFH protein at a total dose of 2.0 mg per administration via ice microneedle patches, twice weekly for a total of 8 doses, starting on the first day of radiotherapy.	Biological: CFH Protein-loaded Ice Microneedles (2.0 mg); Recombinant human CFH protein delivered intradermally via ice microneedle patches at a total dose of 2.0 mg per administration, twice weekly for a total of 8 doses, starting on the first day of radiotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Dose-Limiting Toxicities (DLTs)	Number of participants experiencing DLT within 28 days after the first dose of CFH protein delivered via ice microneedles.	First 28 days after the first study drug administration
Incidence and Severity of Adverse Events (AEs)	Number of participants with adverse events, graded according to NCI CTCAE v5.0.	Total study period up to approximately 6 months post-radiotherapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Irradiated Skin Thickness	Change in skin thickness of the irradiated area measured by ultrasound.	Baseline (pre-radiotherapy) to within 6 months after completion of radiotherapy
Change in Palpable Fibrotic Area (Surface Area and Volume)	Change in surface area (length × width) and volume (surface area × thickness) of palpable skin fibrosis in the irradiated area.	Baseline (pre-radiotherapy) to within 6 months after completion of radiotherapy
Number of Participants with CTCAE Grade ≤2 Fibrosis	Number of participants who develop radiation-induced skin fibrosis of grade ≤2 according to NCI CTCAE v5.0.	Within 6 months after completion of radiotherapy
Change in Skindex Life Quality Index (SQLI) score-16	Change in QoL scores assessed by SQLI-16 questionnaires. Minimum Value：0 Maximum Value：100 Higher Score Means：Worse outcome (higher score indicates greater impairment of quality of life)	Baseline (pre-radiotherapy) to within 6 months after completion of radiotherapy
Change in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) score	Change in QoL scores assessed by QLQ-C30 questionnaires. Minimum Value：0 Maximum Value：100 Higher Score Means：For Global Health Status / QoL scale：Better outcome	Baseline (pre-radiotherapy) to within 6 months after completion of radiotherapy
Change in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Cancer Module (EORTC QLQ-H&N35) score	Change in QoL scores assessed by QLQ-H&N35 questionnaires. Minimum Value：0 Maximum Value：100 Higher Score Means：Worse outcome (higher score indicates more severe symptoms/problems)	Baseline (pre-radiotherapy) to within 6 months after completion of radiotherapy
Change in Dermatology Life Quality Index (DLQI) score	Change in QoL scores assessed by DLQl questionnaires. Minimum Value：0 Maximum Value：30 Higher Score Means：Worse outcome (higher score indicates greater impairment of skin-related quality of life)	Baseline (pre-radiotherapy) to within 6 months after completion of radiotherapy

Collaborators and Investigators

• Sponsor: West China Hospital

Publications and helpful links

General Publications

• Gothard L, Cornes P, Earl J, Hall E, MacLaren J, Mortimer P, Peacock J, Peckitt C, Woods M, Yarnold J. Double-blind placebo-controlled randomised trial of vitamin E and pentoxifylline in patients with chronic arm lymphoedema and fibrosis after surgery and radiotherapy for breast cancer. Radiother Oncol. 2004 Nov;73(2):133-9. doi: 10.1016/j.radonc.2004.09.013.
• Delanian S, Porcher R, Rudant J, Lefaix JL. Kinetics of response to long-term treatment combining pentoxifylline and tocopherol in patients with superficial radiation-induced fibrosis. J Clin Oncol. 2005 Dec 1;23(34):8570-9. doi: 10.1200/JCO.2005.02.4729. Epub 2005 Oct 31.
• Fijardo M, Kwan JYY, Bissey PA, Citrin DE, Yip KW, Liu FF. The clinical manifestations and molecular pathogenesis of radiation fibrosis. EBioMedicine. 2024 May;103:105089. doi: 10.1016/j.ebiom.2024.105089. Epub 2024 Apr 5.
• Jozsi M, Schneider AE, Karpati E, Sandor N. Complement factor H family proteins in their non-canonical role as modulators of cellular functions. Semin Cell Dev Biol. 2019 Jan;85:122-131. doi: 10.1016/j.semcdb.2017.12.018. Epub 2018 Jan 5.
• Straub JM, New J, Hamilton CD, Lominska C, Shnayder Y, Thomas SM. Radiation-induced fibrosis: mechanisms and implications for therapy. J Cancer Res Clin Oncol. 2015 Nov;141(11):1985-94. doi: 10.1007/s00432-015-1974-6. Epub 2015 Apr 25.
• Mayor S. WHO priority list of medical devices for cancer management. Lancet Oncol. 2017 Jul;18(7):856. doi: 10.1016/S1470-2045(17)30407-2. Epub 2017 May 25. No abstract available.

Study record dates

Study Major Dates

• Study Start (Estimated): May 20, 2026
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: April 20, 2026
• First Submitted That Met QC Criteria: April 27, 2026
• First Posted (Actual): May 5, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck
• Other Study ID Numbers: HX 2026-339

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No