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

Official title

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

Overview

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.

Interventions

• 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.
• 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.
• 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.

Primary outcome measures

• Incidence of Dose-Limiting Toxicities (DLTs) [Time frame: First 28 days after the first study drug administration]
• Incidence and Severity of Adverse Events (AEs) [Time frame: Total study period up to approximately 6 months post-radiotherapy]

Secondary outcome measures (7)

• Change in Irradiated Skin Thickness [Time frame: Baseline (pre-radiotherapy) to within 6 months after completion of radiotherapy]
• Change in Palpable Fibrotic Area (Surface Area and Volume) [Time frame: Baseline (pre-radiotherapy) to within 6 months after completion of radiotherapy]
• Number of Participants with CTCAE Grade ≤2 Fibrosis [Time frame: Within 6 months after completion of radiotherapy]
• Change in Skindex Life Quality Index (SQLI) score-16 [Time frame: 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 [Time frame: 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 [Time frame: Baseline (pre-radiotherapy) to within 6 months after completion of radiotherapy]
• Change in Dermatology Life Quality Index (DLQI) score [Time frame: Baseline (pre-radiotherapy) to within 6 months after completion of radiotherapy]

Eligibility criteria

Inclusion criteria

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

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

Exclusion criteria

• 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;
• 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.).
• 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.
• 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.
• Participation in another clinical trial of a drug or device within 3 months prior to screening.
• History of drug abuse or known medical, psychological, or social conditions (e.g., alcoholism or drug addiction).
• Pregnant or breastfeeding women, or women/partners planning pregnancy during the period from screening through 12 months after the last dose.
• Any other condition that, in the investigator's opinion, makes the patient unsuitable for participation in this trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Prevention

Study locations

China · 1 center

• West China Hospital, Sichuan University — Chengdu

Publications

• 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. PMID 29305301
• 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. PMID 16260695
• 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. PMID 15542159
• 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. PMID 38579363
• 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. PMID 25910988
• 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. PMID 28552214

Identifiers

NCT: NCT07567235 · HX 2026-339

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗