Neuromyelitis Optica Spectrum Disorders (NMOSD), Neuropathic Pain
Conditions
Keywords
neuromyelitis optica spectrum disorders, Neuropathic pain, Crisugabalin, NMOSD
Brief summary
This study is a multicenter, prospective, randomized, double-blind, placebo-controlled exploratory investigation conducted in China.
Detailed description
To evaluate the efficacy and safety of Crisugabalin, a China-developed novel third-generation calcium channel modulator, for neuropathic pain in neuromyelitis optica spectrum disorder (NMOSD). Patients are randomized 1:1 to receive Crisugabalin or placebo for 2 weeks , followed by an 8-week open-label extension period .The main questions of this study aim to answer are: Does Crisugabalin lower pain scores after 2 weeks and 10 weeks? What medical problems do participants have when taking crisugabalin? This trial is to compare Crisugabalin to a placebo for the first 2 weeks to see if it reduces pain. Participants will: Take Crisugabalin or a placebo twice daily for 2 weeks (double-blind) Then take Crisugabalin for 8 more weeks (open-label) Visit the clinic at weeks 1, 2, 4, and 8 Complete questionnaires about pain, sleep, spasms, anxiety, and depression Last updated on December 2, 2025
Interventions
DRUGCrisugabalin
Crisugabalin 20-40mg bid
DRUGPlacebo+Crisugabalin
Placebo+Crisugabalin
Sponsors
Tang-Du Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
\*\*Inclusion Criteria:\*\* Subjects who meet all of the following criteria will be enrolled in this study: 1. Able to understand and voluntarily sign the written informed consent form; 2. Male or female aged between 18 years (inclusive) and 75 years; 3. Diagnosed with aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD) according to the International Panel for NMO Diagnosis (IPND, 2015) criteria; 4. Patients with comorbid neuropathic pain, DN4 ≥ 4; no change in medication dosage within the past month; 5. Numeric Rating Scale (NRS) for pain score ≥ 4 at screening; 6. First-time use of Crisugabalin Capsules. \*\*
Exclusion criteria
\*\* Subjects who meet any of the following criteria will not be enrolled in this study: 1. Presence of peripheral neuropathy or pain unrelated to NMOSD that, in the investigator's judgment, may confound the assessment; 2. Known history of allergy to the investigational drug components, or to other drugs with similar chemical structures, or to any excipients; 3. Prior use of pregabalin ≥ 300 mg/day, gabapentin ≥ 1200 mg/day, or mirogabalin ≥ 30 mg/day with lack of clinical efficacy as judged by the investigator; 4. Severe liver or kidney function abnormalities, meeting any of the following clinical laboratory findings: 1\) Liver function: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 × upper limit of normal (ULN); 2) Estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m² (calculated using the simplified MDRD formula); 5. Women who are pregnant, planning to become pregnant during the study period, or currently breastfeeding; subjects who are unwilling to use reliable contraceptive measures (including condoms, spermicides, intrauterine devices, etc.) from the time of signing the ICF until 28 days after the last dose of the investigational drug; 6. Current use of IL-6 receptor blockers (e.g., tocilizumab, satralizumab); 7. History of suicidal behavior or suicidal ideation; 8. Participation in any other clinical study within 30 days prior to screening; 9. The investigator determines that there are other situations in which participation in the study is inappropriate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Numeric Rating Scale (NRS) Pain Score | Change from baseline in the Numeric Rating Scale (NRS) pain score after 2 and 10 weeks of treatment | Patients rate their average pain intensity over the past 24 hours on an 11-point scale (0-10), with 0 = no pain and 10 = worst possible pain. * Min / Max: 0 / 10 * Severity relationship:\*\* Higher scores indicate greater pain severity. Pain levels are categorized as: Mild (1-3), Moderate (4-6), Severe (7-10) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Numeric Rating Scale (NRS) response rate | Change from baseline between Crisugabalin and placebo during the 2-week and 10 -week treatment period. | Proportion of subjects with ≥30% and ≥50% reduction in NRS from baseline between Crisugabalin and placebo during the 2-week and 10 -week treatment period |
| Short-Form McGill Pain Questionnaire (SF-MPQ) score | Change from baseline in the Short-Form McGill Pain Questionnaire (SF-MPQ) score after 2 and 10 weeks of treatment | The Short-Form McGill Pain Questionnaire (SF-MPQ) comprises three main components for pain assessment: 1. Pain Rating Index (PRI): This includes 11 sensory descriptors and 4 affective descriptors. Each item is rated on a 4-point intensity scale: 0 = none, 1 = mild, 2 = moderate, 3 = severe. The PRI yields a total score ranging from 0 to 45 (sensory subscale: 0-33; affective subscale: 0-12). 2. Visual Analogue Scale (VAS): A 10-cm unmarked horizontal line anchored by 0 = no pain and 10 = worst possible pain. Patients mark a cross on the line to indicate their average pain level over the past 24 hours. The score is determined by measuring the distance from the 0 end to the mark (in cm), or by reading directly from a scale on the reverse side. 3. Present Pain Intensity (PPI): A 6-point scale ranging from 0 = no pain to 5 = excruciating pain. Patients select the level that best matches their subjective pain experience at the present moment. Score Ranges: PRI: 0 - 45 VAS: 0 - 10 PPI: 0 - 5 |
| Daily Sleep Interference Scale (DSIS) score | Change from baseline in the Daily Sleep Interference Scale (DSIS) score after 2 and 10 weeks of treatment | * Interpretation:Patients rate how much pain interfered with sleep over the past 24 hours on a 0-10 scale, where 0 = pain does not interfere with sleep and 10 = completely unable to sleep. * Min / Max:0 / 10 * Severity relationship:\*\* Higher scores indicate greater sleep disruption due to pain. |
| Penn Spasm Frequency Scale (PSFS) score | Change from baseline in the Penn Spasm Frequency Scale (PSFS) score after 2 and 10 weeks of treatment | * Interpretation: Two parts - spasm frequency (0-4, where higher = more frequent) and, if present, severity (1 = mild, 2 = moderate, 3 = severe). If frequency = 0, severity is not assessed. * Min / Max:Frequency: 0-4; Severity (if spasms present): 1-3 * Severity relationship: Higher frequency and severity scores indicate more problematic muscle spasms. |
| Hamilton Anxiety Rating Scale (HAMA) score | Change from baseline in the Hamilton Anxiety Rating Scale (HAMA) score after 2 and 10 weeks of treatment | * Interpretation:A clinician-rated scale with 14 items, each scored 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. Total score reflects anxiety severity. * Min / Max: 0 / 56 * Severity relationship: Higher total scores indicate more severe anxiety. |
| Hamilton Depression Rating Scale (HAMD) score | Change from baseline in the Hamilton Depression Rating Scale (HAMD) score after 2 and 10 weeks of treatment | * Interpretation: Clinician-rated scale for depressive symptoms. Most items scored 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe. A few items use a 0-2 scale (0 = absent, 1 = mild-moderate, 2 = severe). * Min / Max:0 / 74 (approximate for 24 items) * Severity relationship: Higher total scores indicate more severe depression. |
| Incidence of adverse reactions | Change from baseline during 2 and 10 weeks of treatment | Treatment-emergent adverse events (TEAEs) and the incidence of TEAEs during the study period for Crisugabalin and placebo. |
| Patient Global Impression of Change (PGIC) score | Change from baseline in the Patient Global Impression of Change (PGIC) score after 10 weeks of treatment | * Interpretation: A 7-point scale assessing overall improvement since treatment began. * 1 = Very much improved * 2 = Much improved * 3 = Minimally improved * 4 = No change * 5 = Minimally worse * 6 = Much worse * 7 = Very much worse * Min / Max: 1 / 7 * Severity relationship: Lower scores indicate greater improvement; higher scores indicate worsening. |
| EuroQol 5-Dimension 5-Level（EQ-5D-5L） score | Change from baseline in the EuroQol 5-Dimension 5-Level（EQ-5D-5L） score after 10 weeks of treatment | * Interpretation: Measures health-related quality of life across 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), each rated 1 = no problems to 5 = extreme problems. A VAS from 0 (worst imaginable health) to 100 (best imaginable health) is also included. * Min / Max: Dimension scores: 1-5 per dimension; VAS: 0-100 * Severity relationship:Higher dimension scores indicate worse function/more problems; higher VAS score indicates better overall health. |
Countries
China
Contacts
CONTACTJun Guo, MD
PRINCIPAL_INVESTIGATORJun Guo
Tang-Du Hospital
Outcome results
None listed