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Phase 3 Trial of AMBTX-01 (neridronate) for Complex Regional Pain Syndrome Type 1
This is a multicenter, randomized, triple-blind, controlled trial, to assess the efficacy, safety, and tolerability of neridronate 400 mg IV in adult participants with the warm subtype of Complex Regional Pain Syndrome Type 1 (CRPS-1) and a positive triple phase bone scan (TPBS).
The total planned trial duration for each participant will be approximately up to 18 weeks and will include:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| neridronate | Experimental | 400 mg AMBTX-01 infusion |
|
| Placebo | Placebo Comparator | Placebo comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Neridronate | Drug | neridronate 100 mg, given as a 2-hour infusion on Days 1, 4, 7, and 10. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in pain intensity from baseline to Week 12. | Assessed on an 11-point Numerical Rating Scale (NRS), with 0 representing no pain and 10 representing the worst possible pain. | Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| At least a 50% reduction from baseline to Week 12 in pain intensity. | Assessed using an 11-point Numerical Rating Scale (NRS), with 0 representing no pain and 10 the worst possible pain. | Week 12 |
| Change from baseline in CRPS Severity Score (CSS) to Week 12. |
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Inclusion Criteria:
Male or female participant ≥ 18 years of age at time of Screening.
A diagnosis of CRPS-1 according to the clinical Budapest Criteria as recommended by the International Association for the Study of Pain (IASP), as well as no known peripheral nerve injury. Signs and symptoms of CRPS must apply to a single identified affected limb (i.e., arm, hand, wrist, leg, ankle or foot) and must demonstrate asymmetry with respect to the contralateral limb.
Single affected limb at the Screening and Randomization Visits meeting the following warm subtype criteria:
Edema in the affected limb
AND ≥ 2 of the following:
≤ 6 months since the onset of CRPS symptoms relative to the Randomization visit
Increased uptake in the involved limb compared to the contralateral limb on TPBS (phase 2 and/or phase 3) during Screening. A historic scan not older than 3 months prior to Randomization Visit is acceptable, if available and of sufficient quality for a central read.
Women of childbearing potential must:
Exception: Women exclusively engaging in same sex sexual activities are not required to meet this criterion.
Adequate compliance with the eDiary during the screening period.
Exclusion Criteria
A current or prior diagnosis of CRPS Type 2 or CRPS not otherwise specified (CRPS NOS), or whose CRPS has no known inciting event, or CRPS-1 without criteria of the warm subtype at the time of Screening.
≥ 40 points on the Pain Catastrophizing Scale.
Prior use of neridronate or participation in a clinical study where the participant may have received neridronate.
The use of any of the following treatments within the timeframe specified from Randomization Visit:
Within the last 12 months:
Within the last 6 months:
Participants currently taking or planning to be treated with prohibited concomitant medications/therapies, or not likely able to follow the protocol restrictions for use of concomitant treatment.
Severely impaired renal function.
Hypocalcemia.
Vitamin D deficiency.
Significant dental findings such as an unhealed tooth extraction site.
Eye inflammation.
Significantly elevated liver-related lab tests or evidence of significant liver disease.
Clinically unstable cardiac disease.
Any known conditions, from 3 months prior to Screening Visit or to the Randomization Visit, that may interfere with the assessment of CRPS-1, CRPS-related pain, safety, or other trial assessments.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| SVP, Clinical Operations | Contact | +1 949-785-4954 | clinicaltrials@ambrostx.com | |
| Ambros Therapeutics, Inc | Contact |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ambros Clinical Trial Site | Recruiting | Phoenix | Arizona | 85032 | United States | |
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| Label | URL |
|---|---|
| Related Info | View source |
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| Placebo |
| Drug |
placebo comparator |
|
Assessed using the CRPS CSS, a 0-16 scale where higher scores denotes greater CRPS symptom severity and lower scores reflect milder symptoms. |
| Week 12 |
| Patient Global Impression of Change (PGI-C) in CRPS-Related Health. | Assessed using the PGI-C, a 7-point numerical rating scale where 1 indicates "very much improved" and 7 indicates "very much worse." | Week 12 |
| Change from baseline in the Short Form 36 (SF-36) Item Health Survey Physical Functioning domain. | Assessed using the SF-36, a validated 36-item self-reported questionnaire that measures health-related quality of life across eight domains: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. Scores range from 0 to 100, with higher scores indicating better health status. | Week 12 |
| Change from baseline over time in pain intensity. | Assessed on an 11-point Numerical Rating Scale (NRS), with 0 representing no pain and 10 representing the worst possible pain. | Day 10, Weeks 3, 6, and 9 |
| At least a 50% reduction from baseline in pain intensity. | Assessed using an 11-point Numerical Rating Scale (NRS), with 0 representing no pain and 10 the worst possible pain. | Day 10, Weeks 3, 6, and 9 |
| At least a 30%, 70%, and 90% reduction from baseline in pain intensity. | Assessed using an 11-point Numerical Rating Scale (NRS), with 0 representing no pain and 10 the worst possible pain. | Day 10, Weeks 3, 6, 9, and 12 |
| Time to onset of analgesic improvement. | Assessed as the time to onset of analgesic improvement, defined by a ≥30% reduction in pain intensity from baseline on the 11-point Numerical Rating Scale (NRS), with 0 representing no pain and 10 the worst possible pain. The improvement must be sustained for a minimum of one week. | daily assessment up to week 12 |
| Time to at least a 50%, 70%, and 90% reduction from baseline in pain intensity. | Assessed using an 11-point Numerical Rating Scale (NRS), with 0 representing no pain and 10 the worst possible pain. | 7-day average |
| Change from baseline in the 7-day mean of daily "pain now". | Assessed on an 11-point Numerical Rating Scale (NRS), with 0 representing no pain and 10 representing the worst possible pain. | Day 10, Weeks 3, 6, 9, and 12 |
| At least a 30%, 50%, 70%, and 90% reduction from baseline in pain intensity. | Assessed using an 11-point Numerical Rating Scale (NRS), with 0 representing no pain and 10 the worst possible pain. | Day 10, Weeks 3, 6, 9, and 12 |
| Change from baseline in 7-day average mean of daily "worst pain" assessment. | Assessed using the average score from the 11-point Numerical Rating Scale (NRS), where 0 denotes no pain and 10 denotes the worst possible pain | Day 10, Weeks, 3, 6, 9, 12 |
| At least a 30%, 50%, 70%, and 90% reduction from baseline in pain intensity | Assessed using the average score of daily "worst pain" from the 11-point Numerical Rating Scale (NRS), where 0 denotes no pain and 10 denotes the worst possible pain | Day 10, Weeks, 3, 6, 9, 12 |
| Change from baseline in pain evoked by active motion. | Assessed using an 11-point Numerical Rating Scale (NRS), with 0 representing no pain and 10 the worst possible pain in the CRPS affected limb. | Day 10, Weeks 3, 6, and 12 |
| At least a 50% reduction from baseline in pain evoked by active motion. | Assessed using an 11-point Numerical Rating Scale (NRS), with 0 representing no pain and 10 the worst possible pain in the affected limb. | Day 10, Weeks 3, 6, 12 |
| Change from baseline in active range of motion (AROM) of affected limb vs. contralateral limb. | Assessed by measuring range of motion of selected joints using a goniometer, and calculating the change from baseline for each joint assessed. | Day 10, Weeks 3, 6, 12 |
| Change from baseline in the CRPS Severity Score (CSS) and in the individual elements of the CRPS Severity Score. | CRPS severity score is a series of 17, 0-1 questions (where 0 is that the sign/symptom is not displayed and 1 is that the sign/symptom is displayed) and scored for a total score of 0 (no CRPS signs/symptoms) to 17 (worse CRPS severity). | Days 4, 7, 10, Weeks 3, and 6 |
| Change from baseline in the CSS self-report (CSS-SR) | CSS-SR is a patient, self-report questionnaire that assess the same 13 concepts of the CSS using yes/no items. Responses are coded as present (1) or absent (0) and summed to yield a total score (range 0-13) | Week 12 |
| Change from base line in edema of affected limb | Assessed using the "edema" using 4-point numerical rating scale where 0 is no edema and 3 is severe edema. | Days 4, 7, 10, Weeks 3, 6, and 12 |
| Change from baseline in temperature of affected limb vs contralateral limb. | Assessment of 'temperature' is defined as the difference in temperature, measured in degrees Celsius (°C) using an infrared thermometer, between the affected limb and the contralateral limb. | Days 4, 7, 10, Weeks 3, 6, and 12 |
| Change from baseline in use of rescue analgesic medications. | Changes from baseline at each time point will be classified as improved (yes-to-no), unchanged (no-to-no or yes-to-yes), or worsened (no-to-yes). | Day 10, Weeks 3, 6, 9, and 12 |
| Change from baseline in mean daily dose of rescue analgesic medicines. | Assessed as the mean daily dose of rescue analgesic medications, calculated over the 7-day period preceding each scheduled timepoint. | Day 10, Weeks 3, 6, 9, and 12 |
| Change from baseline in heavy use of rescue analgesic medications. | Changes from baseline at each time point will be classified as improved (yes-to-no), unchanged (no-to-no or yes-to-yes), or worsened (no-to-yes) where "heavy use" is defined as > 3000 mg acetaminophen > 3 days/week and/or > 5 mg oxycodone > 3 days/week during the 7 days before the given study visit. | Day 10, Weeks 3, 6, 9, and 12 |
| Patient Global Impression of Change (PGI-C) in CRPS-related health. | Assessed using a categorical scale of: "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," and "very much worse," which will be mapped to numeric values of -3, -2, -1, 0, 1, 2, and 3, respectively. | Days 4, 7, 10, Weeks 3, and 6 |
| Clinician Global Impression of Change (CGI-C) in CRPS-related health. | Assessed using a categorical scale of: "very much improved," "much improved," "minimally improved," "no change," "minimally worse," "much worse," and "very much worse," which correspond to numeric values of 0, 1, 2, 3, 4, and 5, respectively. | Days 4, 7, 10, Weeks 3, 6, and 12 |
| Change from baseline in Patient Global Impression of Severity (PGI-S) in CRPS Severity. | Assessed using a categorical scale of: "none," "minimal," "mild," "moderate," "severe," and "very severe," which will be mapped to numeric values of -3, -2, -1, 0, 1, 2, and 3, respectively. | Days 4, 7, 10, Weeks 3, 6, and 12 |
| Change from baseline in Short Form McGill Pain Questionnaire (SF-MPQ) (a) Total Pain Score, (b) each of 4 domain scores, (c) single items. | Assessed using a response to 22 descriptors rated on an 11-point numerical scale (NRS), capturing both neuropathic and non-neuropathic aspects. These descriptors are grouped into four core domains-Continuous Pain, Intermittent Pain, Neuropathic Pain, and Affective Descriptors-with domain scores calculated as the mean of items within each domain. The overall pain score is derived from the average of the 22 items. The complete scale runs from 0 to 10, where a higher score represents greater pain severity. | Days 4, 7, 10, and Weeks 3, 6, and 12 |
| Moderate (at least 30%) and substantial (at least 50%) improvement in Short Form McGill Pain Questionnaire (SF-MPQ) (a) Total Pain Score, and (b) each of 4 domain scores. | Assessed using a response to 22 descriptors rated on an 11-point numerical scale (NRS), capturing both neuropathic and non-neuropathic aspects. These descriptors are grouped into four core domains-Continuous Pain, Intermittent Pain, Neuropathic Pain, and Affective Descriptors-with domain scores calculated as the mean of items within each domain. The overall pain score is derived from the average of the 22 items. The complete scale runs from 0 to 10, where a higher score represents greater pain severity. | Days 4, 7, 10, Weeks 3, 6, and 12 |
| Change from baseline in the Short Form 36 (SF-36) Item Health Survey (a) 8 domain scores and (b) 2 component summary scores. | Assessment focuses on changes across eight domains: Physical Functioning, Role Limitations due to Physical Health, Role Limitations due to Emotional Problems, Energy/Fatigue, Emotional Well-being, and Social Functioning. Two summary scores-Physical Component Summary and Mental Component Summary-are derived. All domain scores are standardized to a 0-100 scale, with higher scores reflecting better health status | Day 10, Weeks 3, 6 |
| Moderate (≥ 30%) and substantial (≥ 50%) improvement in the Short Form 36 (SF-36) Item Health Survey (a) 8 domain scores and (b) 2 component summary scores. | Assessment focuses on changes across eight domains: Physical Functioning, Role Limitations due to Physical Health, Role Limitations due to Emotional Problems, Energy/Fatigue, Emotional Well-being, and Social Functioning. Two summary scores-Physical Component Summary and Mental Component Summary-are derived. All domain scores are standardized to a 0-100 scale, with higher scores reflecting better health status | Days 4, 7, 10, Weeks 3, 6, and 12 |
| Change from baseline in the daily sleep interference scale (DSIS). | Assessed using the 7-day average score on the 11-point Numerical Rating Scale (NRS), where 0 represents did not interfere with sleep and 10 represents completely interfered with sleep - unable to sleep due to CRPS pain. | Day 10, Weeks 3, 6, 9, and 12 |
| Moderate (≥ 30%) and substantial (≥ 50%) improvement in the daily sleep interference scale (DSIS). | Assessed using the 7-day average score on the 11-point Numerical Rating Scale (NRS), where 0 represents did not interfere with sleep and 10 represents completely interfered with sleep - unable to sleep due to CRPS pain. | Day 10, Weeks 3, 6, 9, and 12 |
| Time to moderate (≥ 30%) and substantial (≥ 50%) reduction from baseline in the daily sleep interference scale (DSIS). | Assessed using the 7-day average score on the 11-point Numerical Rating Scale (NRS), where 0 represents did not interfere with sleep and 10 represents completely interfered with sleep - unable to sleep due to CRPS pain. | 7-day average |
| Ambros Clinical Trial Site |
| Recruiting |
| Tucson |
| Arizona |
| 85710 |
| United States |
| Ambros Clinical Trial Site | Recruiting | Napa | California | 94558 | United States |
| Ambros Clinical Trial Site | Recruiting | Pasadena | California | 91105 | United States |
| Ambros Clinical Trial Site | Recruiting | Tustin | California | 92780 | United States |
| Ambros Clinical Trial Site | Recruiting | Washington D.C. | District of Columbia | 20006 | United States |
| Ambros Clinical Trial Site | Recruiting | Brandon | Florida | 33511 | United States |
| Ambros Clinical Trial Site | Recruiting | Daytona Beach | Florida | 32117 | United States |
| Ambros Clinical Trial Site | Recruiting | Pembroke Pines | Florida | 33025 | United States |
| Ambros Clinical Trial Site | Recruiting | Lawrenceville | Georgia | 30046 | United States |
| Ambros Clinical Trial Site | Recruiting | Newnan | Georgia | 30265 | United States |
| Ambros Clinical Trial Site | Recruiting | Chicago | Illinois | 60640 | United States |
| Ambros Clinical Trial Site | Recruiting | Orland Park | Illinois | 60462 | United States |
| Ambros Clinical Trial Site | Recruiting | Shrewsbury | New Jersey | 07702 | United States |
| Ambros Clinical Trial Site | Recruiting | Charlotte | North Carolina | 28211 | United States |
| Ambros Clinical Trial Site | Recruiting | Wilmington | North Carolina | 28412 | United States |
| Ambros Clinical Trial Site | Recruiting | Winston-Salem | North Carolina | 27103 | United States |
| Ambros Clinical Trial Site | Recruiting | Houston | Texas | 77079 | United States |
| ID | Term |
|---|---|
| D020918 | Complex Regional Pain Syndromes |
| D004487 | Edema |
| D010146 | Pain |
| D012019 | Reflex Sympathetic Dystrophy |
| ID | Term |
|---|---|
| D001342 | Autonomic Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D010523 | Peripheral Nervous System Diseases |
| D009468 | Neuromuscular Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009461 | Neurologic Manifestations |
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| ID | Term |
|---|---|
| C053389 | 6-amino-1-hydroxyhexane-1,1-diphosphonate |
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