Complex Regional Pain Syndrome Type IPhase 3CRPS-RISENCT07210515
Evaluation of IV AMBTX-01 (Neridronate) for Treatment of CRPS Type 1 (CRPS-RISE)
A Phase 3 study testing Neridronate in people with Complex Regional Pain Syndrome Type I, run by Ambros Therapeutics, Inc. at 33 sites in United States.
Trial summary
Phase 3 Trial of AMBTX-01 (neridronate) for Complex Regional Pain Syndrome Type 1 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Complex Regional Pain Syndrome Type I
- What is being tested?
- Neridronate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 270 participants
- Where
- 33 sitesUnited States
- Study dates
- 14 Apr 2026to Jan 2028
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- Obvious redness in the affected region relative to the same region on the contralateral limb on inspection
Show all 16Show fewer
- ≥ 1°C increase in temperature on the affected limb relative to the contralateral limb
- Moderate-to-severe edema
- ≤ 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:
- Be nonpregnant.
- Be nonlactating.
- Agree to use a highly effective method of contraception and for at least 6 months following last investigational product administration.
- 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.
Who cannot join
- 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:
- IV bisphosphonates
Show all 21Show fewer
- IV immunoglobulin
- Within the last 6 months:
- Any oral bisphosphonate, denosumab (Prolia®) or receptor activator of nuclear factor kappa B ligand (RANKL) inhibitors (e.g., denosumab biosimilar compounds)
- Calcitonin
- Ketamine
- Radiation therapy to the head or neck
- 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.
Trial locations and contacts
33 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Ambros Therapeutics, Inc contact
33 sites in 1 country
United States33 sites, 33 recruiting
- Recruiting
Ambros Clinical Trial Site
Brandon, Florida, 33511
+1 941-780-9224, sstickels@synergyhealthcorp.com; ckelly@synergyhealthcorp.com
- Recruiting
Ambros Clinical Trial Site
Charlotte, North Carolina, 28211
+1 704-405-3150, shill@qccresearch.com
- Recruiting
Ambros Clinical Trial Site
Charlottesville, Virginia, 22903
+1 434-688-6678, MI9K@uvahealth.org
- Recruiting
Ambros Clinical Trial Site
Chicago, Illinois, 60612
312-563-2028, rachel_granito@rush.edu
- Recruiting
Ambros Clinical Trial Site
Cleveland, Ohio, 44130
+1 440-234-5700, jheil@northstarresearch.org
- Recruiting
Ambros Clinical Trial Site
Dayton, Ohio, 45432
+1 937-252-2000 ext 251, bkulkarni@metamedresearch.com
- Recruiting
Ambros Clinical Trial Site
Daytona Beach, Florida, 32117
+1 386-278-8000, awillhoite@arrowtrials.com
- Recruiting
Ambros Clinical Trial Site
Dearborn, Michigan, 48126
248-721-9539, patientrecruitment@rev-research.com
- Recruiting
Ambros Clinical Trial Site
Fort Worth, Texas, 76244
+1 214-884-7558, mavalos@stryderesearch.com
- Recruiting
Ambros Clinical Trial Site
Houston, Texas, 77079
+1 832-969-6157, sekeia.willis@sclamanagement.com
- Recruiting
Ambros Clinical Trial Site
La Jolla, California, 92093
858-822-0787, vpolk@health.ucsd.edu
- Recruiting
Ambros Clinical Trial Site
Lawrenceville, Georgia, 30046
+1 470-657-6031, mosyaw.stephens@skycrng.com
- Recruiting
Ambros Clinical Trial Site
Little Rock, Arkansas, 72205
+1 501-398-8622, HHattabaugh@uams.edu
- Recruiting
Ambros Clinical Trial Site
Lubbock, Texas, 79410
+1 806-891-3292, keely.esch@sclamanagement.com
- Recruiting
Ambros Clinical Trial Site
Mesquite, Texas, 75150
- Recruiting
Ambros Clinical Trial Site
Mesquite, Texas, 75150
+1 972 599-1530, DeZaria.kidd@citplano.com
- Recruiting
Ambros Clinical Trial Site
Napa, California, 94558
+1 707-252-9606, nichole@neurovations.com
- Recruiting
Ambros Clinical Trial Site
Newnan, Georgia, 30265
+1 770-755-6914, dhelton@vistaclinresearch.com
- Recruiting
Ambros Clinical Trial Site
Orland Park, Illinois, 60462
+1 646-744-5943, nag@m1-health.com
- Recruiting
Ambros Clinical Trial Site
Overland Park, Kansas, 66210
+1 913-825-2314, amy.r@neuroscienceresearchctr.com
- Recruiting
Ambros Clinical Trial Site
Pasadena, California, 91105
grazy@havanaresearchinstitute.com
- Recruiting
Ambros Clinical Trial Site
Pembroke Pines, Florida, 33025
+1 954-852-5484, a.garciaduconge@optimumcareresearch.com
- Recruiting
Ambros Clinical Trial Site
Phoenix, Arizona, 85032
+1 602-288-4673, shana.harshell@hriaz.com
- Recruiting
Ambros Clinical Trial Site
Reno, Nevada, 89511
775-284-8650, madeline@nvadvancedpain.com
- Recruiting
Ambros Clinical Trial Site
Richmond, Virginia, 23238
+1 804-330-2611, crc2@vaispine.com
- Recruiting
Ambros Clinical Trial Site
Santa Monica, California, 90404
+1 310-264-7246, kguzman@crpscenter.com
- Recruiting
Ambros Clinical Trial Site
Seattle, Washington, 98195
+1 206-807-1430, crpsrise@uw.edu
- Recruiting
Ambros Clinical Trial Site
Shrewsbury, New Jersey, 07702
732-380-0200 EXT 65509, KGee@treatingpain.com
- Recruiting
Ambros Clinical Trial Site
Tucson, Arizona, 85710
+1 520-495-4680, melissa@qlmc.com
- Recruiting
Ambros Clinical Trial Site
Tustin, California, 92780
+1 562-652-0005, hikyhe@solacecr.com
- Recruiting
Ambros Clinical Trial Site
Washington D.C., District of Columbia, 20006
+1 202-808-8295, drdesai@isppcenter.com
- Recruiting
Ambros Clinical Trial Site
Wilmington, North Carolina, 28412
+1 910-408-5746, ffilsell@wakeresearch.com
- Recruiting
Ambros Clinical Trial Site
Winston-Salem, North Carolina, 27103
+1 336-765-6181, Hreyna@ccrpain.com
About this study
Official title: A Randomized, Triple-blind, Placebo-controlled, Phase 3 Trial to Evaluate the Efficacy, Safety, and Tolerability of Intravenous AMBTX-01 (Neridronate) for Treatment of Complex Regional Pain Syndrome Type 1 (CRPS-RISE)
Phase 3 Trial of AMBTX-01 (neridronate) for Complex Regional Pain Syndrome Type 1
Read the detailed description
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:
- Screening period of 2 up to 6 weeks
- Treatment period on Days 1, 4, 7, and 10
- Post-treatment follow-up through week 12
- Conditions
- Complex Regional Pain Syndrome Type I
- Being tested
- Neridronate, Placebo
- Keywords
- CRPS, edema, pain, RDS, CRPS-1, CRPS-I, CRPS Type 1, CRPS 1, CRPS I, CRPS-Type 1, CRPS-Type I, CRPS Type I
- Medical subject headings
- Complex Regional Pain Syndromes, Edema, Pain, Reflex Sympathetic Dystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeridronateDrug
neridronate 100 mg, given as a 2-hour infusion on Days 1, 4, 7, and 10.
PlaceboDrug
placebo comparator
| Study group | Role | What they receive |
|---|---|---|
| neridronate | Experimental | 400 mg AMBTX-01 infusion Receives: Drug: Neridronate |
| Placebo | Placebo comparator | Placebo comparator Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 12
Secondary outcomes (33)
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.
Measured: Week 12
Change from baseline in CRPS Severity Score (CSS) to Week 12.
Assessed using the CRPS CSS, a 0-16 scale where higher scores denotes greater CRPS symptom severity and lower scores reflect milder symptoms.
Measured: 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."
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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 1, 2, 3, 4, 5, 6, and 7, respectively.
Measured: 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 1, 2, 3, 4, 5, 6, and 7, respectively.
Measured: 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 0, 1, 2, 3, 4, and 5, respectively.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 7-day average
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2025
- Study start14 Apr 2026
- Primary completionDec 2027 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Complex Regional Pain Syndrome Type IStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 270 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ambros Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07210515
- Sponsor's protocol ID
- AMBTX-01-301
- Acronym
- CRPS-RISE
- Status last verified
- Oct 2026
- First submitted
- 17 Sep 2025
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Triple-blind, Placebo-controlled, Phase 3 Trial to Evaluate the Efficacy, Safety, and Tolerability of Intravenous AMBTX-01 (Neridronate) for Treatment of Complex Regional Pain Syndrome Type 1 (CRPS-RISE)
- ClinicalTrials.gov ID
- NCT07210515
- Acronym / sponsor ID
- CRPS-RISE / AMBTX-01-301
- Conditions
- Complex Regional Pain Syndrome Type I
- Keywords
- CRPS, edema, pain, RDS, CRPS-1, CRPS-I, CRPS Type 1, CRPS 1
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 270 participants (estimated)
- Lead sponsor
- Ambros Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 14 Apr 2026 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Jan 2028 (estimated)
- First posted
- 7 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 3 Trial of AMBTX-01 (neridronate) for Complex Regional Pain Syndrome Type 1
Detailed description
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:
- Screening period of 2 up to 6 weeks
- Treatment period on Days 1, 4, 7, and 10
- Post-treatment follow-up through week 12
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| neridronate | Experimental | Drug: Neridronate400 mg AMBTX-01 infusion |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo comparator |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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:
- ≤ 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.
Key exclusion criteria (21 listed)
- 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:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Neridronateneridronate 100 mg, given as a 2-hour infusion on Days 1, 4, 7, and 10. | Drug | neridronate |
| Placeboplacebo comparator | Drug | Placebo |
Primary outcome
Change in pain intensity from baseline to Week 12.
Time frame: Week 12
Assessed on an 11-point Numerical Rating Scale (NRS), with 0 representing no pain and 10 representing the worst possible pain.
33 secondary outcomes
At least a 50% reduction from baseline to Week 12 in pain intensity.
Time frame: Week 12
Change from baseline in CRPS Severity Score (CSS) to Week 12.
Time frame: Week 12
Patient Global Impression of Change (PGI-C) in CRPS-Related Health.
Time frame: Week 12
Change from baseline in the Short Form 36 (SF-36) Item Health Survey Physical Functioning domain.
Time frame: Week 12
Change from baseline over time in pain intensity.
Time frame: Day 10, Weeks 3, 6, and 9
At least a 50% reduction from baseline in pain intensity.
Time frame: Day 10, Weeks 3, 6, and 9
At least a 30%, 70%, and 90% reduction from baseline in pain intensity.
Time frame: Day 10, Weeks 3, 6, 9, and 12
Time to onset of analgesic improvement.
Time frame: daily assessment up to week 12
Time to at least a 50%, 70%, and 90% reduction from baseline in pain intensity.
Time frame: 7-day average
Change from baseline in the 7-day mean of daily "pain now".
Time frame: Day 10, Weeks 3, 6, 9, and 12
At least a 30%, 50%, 70%, and 90% reduction from baseline in pain intensity.
Time frame: Day 10, Weeks 3, 6, 9, and 12
Change from baseline in 7-day average mean of daily "worst pain" assessment.
Time frame: Day 10, Weeks, 3, 6, 9, 12
At least a 30%, 50%, 70%, and 90% reduction from baseline in pain intensity
Time frame: Day 10, Weeks, 3, 6, 9, 12
Change from baseline in pain evoked by active motion.
Time frame: Day 10, Weeks 3, 6, and 12
At least a 50% reduction from baseline in pain evoked by active motion.
Time frame: Day 10, Weeks 3, 6, 12
Change from baseline in active range of motion (AROM) of affected limb vs. contralateral limb.
Time frame: 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.
Time frame: Days 4, 7, 10, Weeks 3, and 6
Change from baseline in the CSS self-report (CSS-SR)
Time frame: Week 12
Change from base line in edema of affected limb
Time frame: Days 4, 7, 10, Weeks 3, 6, and 12
Change from baseline in temperature of affected limb vs contralateral limb.
Time frame: Days 4, 7, 10, Weeks 3, 6, and 12
Change from baseline in use of rescue analgesic medications.
Time frame: Day 10, Weeks 3, 6, 9, and 12
Change from baseline in mean daily dose of rescue analgesic medicines.
Time frame: Day 10, Weeks 3, 6, 9, and 12
Change from baseline in heavy use of rescue analgesic medications.
Time frame: Day 10, Weeks 3, 6, 9, and 12
Patient Global Impression of Change (PGI-C) in CRPS-related health.
Time frame: Days 4, 7, 10, Weeks 3, and 6
Clinician Global Impression of Change (CGI-C) in CRPS-related health.
Time frame: Days 4, 7, 10, Weeks 3, 6, and 12
Change from baseline in Patient Global Impression of Severity (PGI-S) in CRPS Severity.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Days 4, 7, 10, Weeks 3, 6, and 12
Change from baseline in the daily sleep interference scale (DSIS).
Time frame: Day 10, Weeks 3, 6, 9, and 12
Moderate (≥ 30%) and substantial (≥ 50%) improvement in the daily sleep interference scale (DSIS).
Time frame: 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).
Time frame: 7-day average
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Trial WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
Related trials for Complex Regional Pain Syndrome Type I
Enrolling by invitationPhase 4
Low Dose Naltrexone Therapy for Complex Regional Pain Syndrome
Complex Regional Pain Syndrome, Chronic Pain
RecruitingPhase 3
Phase 3, Open-Label Extension Study of AMBTX-01 (Neridronate) for Complex Regional Pain Syndrome Type 1
Complex Regional Pain Syndrome Type I
RecruitingObservational study
CRPS-RISE Outcomes Registry
Complex Regional Pain Syndrome I (CRPS I)
Recruiting
ESWT for CRPS-I After Distal Radius Fracture
Complex Regional Pain Syndrome Type I (CRPS-I), Distal Radius Fracture
Recruiting
CRPS-Hand: Contrast + Compression vs Whirlpool
Complex Regional Pain Syndrome I (CRPS I)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ambros Therapeutics, Inc contact
33 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Neridronate in people with Complex Regional Pain Syndrome Type I, run by Ambros Therapeutics, Inc. at 33 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Medical Affairs (+1 949-508-0173, Medinfo@ambrostx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in pain intensity from baseline to Week 12. (time frame: Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.