CREATE-1: A Study to Assess the Efficacy and Safety of AXS-02 in Patients With CRPS-1

Study Overview
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Brief Summary
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This is a randomized, double-blind, placebo-controlled, 24-week study to evaluate the efficacy and safety of AXS-02 in patients with CRPS-I.

Official Title
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CREATE-1 Study: CRPS Treatment Evaluation 1 Study. A Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of AXS-02 (Oral Zoledronate) Administered Orally to Subjects With Complex Regional Pain Syndrome Type I (CRPS-I)

Conditions
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Complex Regional Pain Syndrome, Reflex Sympathetic Dystrophy

Intervention / Treatment
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* Drug: AXS-02 (oral zoledronate)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female of at least 18 years of age Recently confirmed diagnosis of CRPS-1 (Budapest criteria) Average pain intensity score of ≥ 5 (based on an 11-point scale [0 - 10]) Willing and able to provide written informed consent Key Exclusion Criteria: Received chronic opioid therapy within 4 weeks Received a sympathetic nerve block within 3 weeks Active litigation or a pending workers' compensation decision Any other clinically significant medical or pain condition (eg, Parkinson's disease, cognitive impairment, or fibromyalgia) or clinical laboratory abnormality that would in the investigator's judgment interfere with the subject's ability to participate in the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AXS-02 (oral zoledronate)<br>Administered orally in the morning on Days 1, 8, 15, 22, 29, and 36 | Drug: AXS-02 (oral zoledronate)<br>* Once weekly for 6 weeks<br>|
| Placebo Comparator: Placebo<br>Administered orally in the morning on Day 1, 8, 15, 22, 29, and 36 | Drug: Placebo<br>* Once weekly for 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in patient reported pain intensity | Patient reported pain intensity is recorded as an average daily pain intensity using an 11-point scale (0 = no pain to 10 = worst pain possible). | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Brief Pain Inventory (BPI) Pain Score | The BPI is a nine-question survey completed by the patient that assesses quality of life and health status. BPI scores range from 0 to 10, with higher values indicating greater pain. | Baseline to Week 12 | 
| Patients' Global Impression of Change (PGI-C) | The PGI-C is a patient/patient's caregiver rated scale to assess the patients overall treatment response. PGI-C is a 7-point (1-7) scale rated as; very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. | Baseline to Week 12 | 
| Clinicians' Global Impression of Change (CGI-C) | The CGI-C is an investigator-rated scale to assess the overall treatment response. CGI-C is a 7-point (1-7) scale rated as; very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse. | Baseline to Week 12 | 
| Change in EuroQOL 5-dimensions questionnaire (EQ-5D) | The EQ-5D descriptive system comprised the following 5 dimensions: mobility, self care, usual activities, pain/discomfort, and anxiety/depression. Each dimension is rated by the patient at one of 5 levels, with level 1 indicating the best health state (no problems) and level 5 indicating worst health state (e.g., unable to walk about). | Baseline to Week 12 | 
| Change in Short-Form McGill Pain Questionnaire (SF-MPQ-2) | The SF-MPQ-2 measures both neuropathic and nonneuropathic pain. It contains a total of 22 descriptors, which are rated on an intensity scale of 0 = None, to 10 = Worst Possible. | Baseline to Week 12 | 
| Change in bone turnover markers | Bone turnover is measured from 2 biomarkers collected from peripheral blood samples: serum carboxy terminal telopeptide of collagen type I (CTX) and serum procollagen type I N terminal propeptide (s-P1NP). | Baseline to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bisphosphonate, CRPS, RSD, non-opioid, CRPS-1, acute on chronic pain, chronic pain, zoledronic acid