Crisugabalin for Radiotherapy-Related Neuropathic Pain

Phase 2

Recruiting

• Conditions: Neuropathic Pain
• Interventions: Drug: Crisugabalin; Drug: Pregabalin

• Registration Number: NCT06766916
• Lead Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Brief Summary

The purpose of this study is to evaluate whether Crisugabalin has similar efficacy compared to Pregabalin in reducing radiotherapy-related neuropathic pain (RRNP) in patients with head and neck cancers.

Detailed Description

The primary objective of this study is to determine whether Crisugabalin provides non-inferior pain relief compared to Pregabalin in patients with head and neck cancer experiencing radiotherapy-related neuropathic pain. The trial adopts a multicenter, randomized, open-label design, and the primary endpoint is the change in Numeric Rating Scale (NRS) pain scores from baseline to 4 weeks. The study aims to provide new evidence to support treatment strategies for this condition, which significantly affects patients' quality of life.

Study Timeline

• Study First Submitted: 2025-01-05
• Study First Submitted QC: 2025-01-05
• Study First Posted: 2025-01-09
• Status Verified: 2025-02
• Study Start: 2025-05-07
• Last Update Submitted: 2025-05-14
• Last Update Posted: 2025-05-18
• Primary Completion: 2026-11-30
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 172

Inclusion Criteria

1. Ability to understand and voluntarily sign a written informed consent form.
2. Male or female patients aged ≥18 years with an expected survival of at least 5 months.
3. Histologically confirmed head and neck tumors treated with radiotherapy at least 6 months prior to screening.
4. Average NRS pain score ≥4 over 7 days during the screening period, with pain localized to nerve-innervated areas corresponding to the radiotherapy site, such as the head, face, neck, and arms.
5. Diagnosis of neuropathic pain persisting for at least 4 weeks, confirmed by two trained neurologists based on clinical history, symptoms, signs, and a Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) score ≥12 (Chinese version).
6. Adequate cognitive and language abilities to communicate and complete study questionnaires.

Exclusion Criteria

1. Severe abnormalities in hematological, hepatic, or renal function, as evidenced by:

   • Hematology: Neutrophil count <1.5×10⁹/L, platelet count <90×10⁹/L, or hemoglobin <100 g/L.
   • Liver function: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3× upper limit of normal (ULN), or total bilirubin (TBIL) >1.5× ULN.
   • Renal function: Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² or undergoing dialysis.
   • Creatine kinase >2× ULN.

2. Chronic systemic diseases that may interfere with study participation, including but not limited to:

   • Severe cardiopulmonary diseases such as unstable angina, myocardial infarction, severe arrhythmia, WHO functional classification III-IV heart failure, uncontrolled hypertension (systolic BP >160 mmHg or diastolic BP >100 mmHg), or recurrent asthma.
   • Chronic gastrointestinal diseases, such as liver fibrosis, recurrent indigestion or diarrhea, or peptic ulcers.
   • Neurological or psychiatric conditions affecting pain assessment, including epilepsy, recurrent dizziness, headache, memory, or cognitive disorders; cerebrovascular accidents or transient ischemic attacks within 6 months of screening.

3. Known allergy to study drugs or chemically related compounds.

4. Current diagnosis of tumor recurrence or metastasis associated with tumor-related pain.

5. Neuropathic pain not caused by radiotherapy, such as postherpetic neuralgia, diabetic neuropathy, HIV-related neuropathy, spinal cord injury, or other neurological diseases.

6. Use of pregabalin/crisugabalin within 4 weeks before screening.

7. Pregnant, planning to become pregnant during the study, or breastfeeding. Participants and their partners unwilling to use reliable contraception (e.g., condoms, spermicides, intrauterine devices) from the time of consent until 28 days after the last dose of study medication.

8. Participation in any other clinical trial within 30 days prior to screening.

9. Any other condition deemed unsuitable for study participation by the investigator.

10. Use of prohibited medications within at least 5 half-lives of the drug before screening, with prohibition maintained throughout the study.

11. Previous use of pregabalin ≥300 mg/day or gabapentin ≥1200 mg/day deemed ineffective.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Crisugabalin	Crisugabalin	The initial dose is one Crisugabalin capsule (20 mg) taken twice daily. The dose will be gradually increased to the maximum tolerated dose or the maximum daily dose of three capsules (60 mg) taken twice daily.
Pregabalin	Pregabalin	The initial dose is one capsule of Pregabalin (75 mg) taken twice daily. The dose will be gradually increased to the maximum tolerated dose or the maximum daily dose of four capsules (300 mg) taken twice daily.

Primary Outcome Measures

Name	Time	Method
Numeric Rating Scale (NRS) Change	4 weeks	The change in NRS score from baseline to Week 4 of treatment. The NRS measures pain intensity on a scale of 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable pain.

Secondary Outcome Measures

Name	Time	Method
Patient Global Impression of Change (PGIC)	4 weeks	PGIC is a 7 point scale depicting a patient's rating of overall improvement, with 1 representing very much improved and 7 representing very much worse.
Numeric Rating Scale (NRS) Change	1 week	The change in NRS score from baseline to Week 1 of treatment. The NRS measures pain intensity on a scale of 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable pain.
Visual Analogue Scale (VAS) Change	4 weeks	The VAS measures pain intensity on a 0-100 mm scale, with 0 representing no pain and 100 representing the worst imaginable pain.
Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD) scores	4 weeks	The HAMA and HAMD are used to evaluate anxiety and depressive symptoms, respectively.
Daily Sleep Interference Scale (DSIS)	4 weeks	The DSIS measures the impact of pain on sleep quality. Scores range from 0 (no interference) to 10 (complete interference).
Health Status According to EuroQol-5-Domain-5-Level health questionnaire (EQ-5D-5L)	4 weeks	The EQ-5D-5L assessed quality of life based on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The participant was asked to 'check the ONE box that best describes your health TODAY,' choosing from 5 options (no problems, slight problems, moderate problems, severe problems, extreme problems) provided under each dimension.; The health state index value is a single value on a scale from 0 to 100 scores indicating better health: 0 = indicating worst health and 100 = best imaginable health.
Response Rates	4 weeks	The proportion of patients achieving ≥30% and ≥50% reductions in NRS score from baseline to Week 4.
Short-Form McGill Pain Questionnaire (SF-MPQ)	4 weeks	Participants rate their pain in three parts of the questionnaire, which are combined into a single pain intensity score: Part 1 - fifteen descriptors of pain intensity, on a scale of 0 (none) to 3 (severe); Part 2 - the VAS, in which the participant rates pain on a 100 mm-long horizontal line, where 0 mm = no pain and 100 mm = worst possible pain; Part 3 - a present pain intensity index in which the participant rates present pain intensity on a scale of 0 (no pain) to 5 (most intense pain).

Trial Locations

Locations (11)

Fujian Cancer Hospital; 🇨🇳 Fuzhou, Fujian, China

Sun Yat-sen Memorial Hospital, Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China

Sun Yat-sen University Cancer Center; 🇨🇳 Guangzhou, Guangdong, China

Affillated Cancer Hospital and Institute of Guangzhou Medical University; 🇨🇳 Guangzhou, Guangdong, China

Changsha Central Hospital; 🇨🇳 Changsha, Hunan, China

The Affiliated Brain Hospital, Guangzhou Medical University; 🇨🇳 Guangzhou, Guangdong, China

Zhongshan People's Hospital; 🇨🇳 Zhongshan, Guangdong, China

The First Affiliated Hospital of Guangxi Medical University; 🇨🇳 Nanning, Guangxi, China

Henan Cancer Hospital (Affiliated Cancer Hospital of ZhengzhouUniversity); 🇨🇳 Zhengzhou, Henan, China

Hunan Provincial People's Hospital; 🇨🇳 Changsha, Hunan, China

Hunan Brain Hospital; 🇨🇳 Changsha, Hunan, China