Complex Regional Pain Syndrome Type IPhase 3NCT07857733
Phase 3, Open-Label Extension Study of AMBTX-01 (Neridronate) for Complex Regional Pain Syndrome Type 1
A Phase 3 study testing Neridronate in people with Complex Regional Pain Syndrome Type I, run by Ambros Therapeutics, Inc. at 1 site in United States.
Trial summary
A Phase 3 open-label extension study 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?
- No, everyone receives an active treatment
- How many people
- 135 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Oct 2026to 15 Feb 2029
- 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
- Participants must have completed the Week 12 visit of the neridronate AMBTX-01-301 Randomized Clinical Trial (RCT).
- Both the Investigator and participant must agree that the participant is reasonably likely to benefit from neridronate therapy without undue risk based on information about benefits/risks in the IB.
- The Investigator must characterize the participants CRPS-1 as a serious condition based on the presence of persistent moderate-to-severe pain or/and persistent moderate-to-severe CRPS-1 signs or/and symptoms other than pain.
- Participants must be capable of understanding the study requirements and willing to provide informed consent prior to any study-related procedures.
- Participants must be willing and able to comply with the scheduled treatment plan including 4 infusion visits and safety-related assessments.
- Participants must have adequate venous access to enable blood sampling and 4 IV infusions.
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- Women of childbearing potential must:
- Be nonpregnant as determined by a negative highly sensitive urine pregnancy test on every visit before neridronate administration.
- Be nonlactating.
- Agree to use a highly effective method of contraception from at least 28 days prior to treatment for oral contraception (or at least 1 week longer than specified by the manufacturer for other contraceptives) and for at least 6 months following last neridronate administration.
- Exception: Women exclusively engaging in same sex sexual activities are not required to meet this criterion.
Who cannot join
- Individuals who did not participate in AMBTX-01-301 RCT, or those participants from AMBTX-01-301 RCT who discontinued investigational product and/or were withdrawn from the trial.
- Evidence of severely impaired renal function .
- Prior or planned renal transplant.
- The use of any of the following treatments within the timeframe specified from initiation of treatment with neridronate and through the study:
- Within the last 12 months - IV immunoglobulin, any IV bisphosphonates (excluding investigational product as part of AMBTX-01-301 RCT prior to open-label treatment);
- 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;
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- Within the last 3 months: Cinacalcet, Monoclonal antibody peptides against calcitonin gene-related peptide (CGRP), spinal cord stimulation, radiofrequency ablation, peripheral nerve stimulation and other procedural forms of neuromodulation
- Within the last 1 month - Any systemic corticosteroid (intranasal, inhaled, or topical corticosteroids are acceptable)
- Within 2 weeks - Lidocaine infusion, somatic or sympathetic nerve blocks, acupuncture, electromagnetic field treatment, scrambler therapy, dorsal root ganglia (DRG) block, initiation or implementation of radiofrequency ablation or other sympathectomy procedures
- Hypocalcemia, or high risk for hypocalcemia
- Vitamin D deficiency
- Serum potassium or magnesium outside of the laboratory's reference range at Screening
- Elevated liver-related lab tests or evidence of significant liver disease
- Significant dental findings.
- Eye inflammation
- Clinically unstable cardiac disease
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Ambros Clinical Study Site
Phoenix, Arizona, 85032
+1 602-288-4673, shana.harshell@hriaz.com
About this study
Official title: An Open-Label, Phase 3 Study to Evaluate the Safety, Tolerability, and Efficacy of Intravenous AMBTX-01 (Neridronate) for the Treatment of Complex Regional Pain Syndrome Type 1
A Phase 3 open-label extension study of AMBTX-01 (neridronate) for Complex Regional Pain Syndrome Type 1
Read the detailed description
This is a multicenter, open-label extension study to assess the safety, tolerability, and efficacy of IV neridronate 400 mg in eligible participants who have completed the Phase 3 AMBTX-01-301 Randomized Clinical Trial.
The total planned trial duration for each participant will be approximately up to 24 weeks and will include:
- Screening period of up to 12 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
- Keywords
- CRPS-1, Pain, edema
- Medical subject headings
- Complex Regional Pain Syndromes, Pain, Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeridronateDrug
100 mg, given as a 2-hour infusion on Days 1, 4, 7, and 10.
| Study group | Role | What they receive |
|---|---|---|
| Neridronate | Experimental | 400 mg AMBTX-01 infusion Receives: Drug: Neridronate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Treatment Emergent Adverse Events (TEAEs), Acute Phase Reaction (APRs) and Treatment Emergent Serious Adverse Events (TESAEs) and Suspected Unexpected Serious Adverse Events (SUSARs) during the Open Label Extension Study.
Endpoints will be summarized descriptively. Descriptive statistics for categorical variables will be frequencies and percentages. Descriptive statistics for continuous variables will be means, standard deviations, medians, minimums, and maximums.
Measured: Week 12
Secondary outcomes (19)
Change in "average pain" from baseline
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 12
At least a 30%, 50%, 70%, and 90% reduction of "average pain" from baseline
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 12
Change from baseline in "pain now"
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 12
At least a 30%, 50%, 70%, and 90% reduction from baseline in "pain now"
Assessed using an 11-point Numerical Scale (NRS) with 0 representing no pain and 10 the worst possible pain
Measured: Day 10, Weeks 3, 6, and 12
Change from baseline in "worst pain"
Assessed using an 11-point Numerical Rating Scale (NRS), with 0 representing no pain and 10 the worst possible pain.
Measured: Week 12
At least a 30%, 50%, 70%, and 90% reduction from baseline of "worst pain"
Assessed using an 11-point Numerical Rating Scale (NRS), with 0 representing no pain and 10 the worst possible pain.
Measured: Day 10 and Weeks 3, 6, and 12
Change from baseline in the CRPS Severity Score (CSS)
Assessed using the CRPS CSS, a 0-16 scale where higher scores denotes greater CRPS symptom severity and lower scores reflect milder symptoms.
Measured: Day 10, Weeks 3, 6, and 12
Change from baseline to Week 12 in the CSS self-report (CSS-SR).
Assessed using the CRPS CSS-SR, a 0-13 scale where higher scores denotes greater CRPS symptom severity and lower scores reflect milder symptoms.
Measured: Week 12
Change from baseline in edema of affected limb
Assessed using the "edema" 4-point numerical rating scale where 0 is no edema and 3 is severe edema.
Measured: Day 10, Weeks 3, 6, and 12
Change from baseline in temperature (°C) of the 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: Day 10 and Weeks 3, 6, 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, or 7 respectively.
Measured: Day 10 and Weeks 3, 6, and 12
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, 5, 6 and 7 respectively.
Measured: Day 10 and 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: "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, 5, 6 and 7 respectively.
Measured: Day 10 and Weeks 3, 6, and 12
Change from baseline in Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2) (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: Day 10 and Weeks 3, 6, and 12
Moderate (at least 30%) and substantial (at least 50%) improvement from baseline in SF-MPQ-2 (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: Day 10 and Weeks 3, 6, and 12
Change from baseline in the 36-item Short Form 36 Item Health Survey [SF-36] (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 and Weeks 3, 6, and 12
Moderate (at least 30%) and substantial (at least 50%) improvement from baseline in the SF-36 (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 and Weeks 3, 6, and 12
Change from baseline in the Daily Sleep Interference Scale (DSIS) assessment on an 11-point NRS.
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 and Weeks 3, 6, and 12
Moderate (at least 30%) and substantial (at least 50%) improvement from baseline in the DSIS assessment.
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 and Weeks 3, 6, and 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2026
- Study start13 Oct 2026
- Primary completion31 Dec 2028 (estimated)
- Study completion15 Feb 2029 (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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 135 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ambros Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gail Cawkwell, MD, PhD, Study director, Ambros Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07857733
- Sponsor's protocol ID
- AMBTX-01-302
- Status last verified
- Oct 2026
- First submitted
- 24 Sep 2026
- Last updated
- 16 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 16 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Phase 3 Study to Evaluate the Safety, Tolerability, and Efficacy of Intravenous AMBTX-01 (Neridronate) for the Treatment of Complex Regional Pain Syndrome Type 1
- ClinicalTrials.gov ID
- NCT07857733
- Acronym / sponsor ID
- AMBTX-01-302
- Conditions
- Complex Regional Pain Syndrome Type I
- Keywords
- CRPS-1, Pain, edema
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 135 participants (estimated)
- Lead sponsor
- Ambros Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 Oct 2026 (actual)
- Primary completion
- 31 Dec 2028 (estimated)
- Study completion
- 15 Feb 2029 (estimated)
- First posted
- 5 Oct 2026 (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.
A Phase 3 open-label extension study of AMBTX-01 (neridronate) for Complex Regional Pain Syndrome Type 1
Detailed description
This is a multicenter, open-label extension study to assess the safety, tolerability, and efficacy of IV neridronate 400 mg in eligible participants who have completed the Phase 3 AMBTX-01-301 Randomized Clinical Trial.
The total planned trial duration for each participant will be approximately up to 24 weeks and will include:
- Screening period of up to 12 weeks
- Treatment period on Days 1, 4, 7, and 10
- Post-treatment follow-up through Week 12
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neridronate | Experimental | Drug: Neridronate400 mg AMBTX-01 infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Participants must have completed the Week 12 visit of the neridronate AMBTX-01-301 Randomized Clinical Trial (RCT).
- Both the Investigator and participant must agree that the participant is reasonably likely to benefit from neridronate therapy without undue risk based on information about benefits/risks in the IB.
- The Investigator must characterize the participants CRPS-1 as a serious condition based on the presence of persistent moderate-to-severe pain or/and persistent moderate-to-severe CRPS-1 signs or/and symptoms other than pain.
- Participants must be capable of understanding the study requirements and willing to provide informed consent prior to any study-related procedures.
- Participants must be willing and able to comply with the scheduled treatment plan including 4 infusion visits and safety-related assessments.
Key exclusion criteria (16 listed)
- Individuals who did not participate in AMBTX-01-301 RCT, or those participants from AMBTX-01-301 RCT who discontinued investigational product and/or were withdrawn from the trial.
- Evidence of severely impaired renal function .
- Prior or planned renal transplant.
- The use of any of the following treatments within the timeframe specified from initiation of treatment with neridronate and through the study:
- Hypocalcemia, or high risk for hypocalcemia
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 |
|---|---|---|
| Neridronate100 mg, given as a 2-hour infusion on Days 1, 4, 7, and 10. | Drug | Neridronate |
Primary outcome
Number of Participants with Treatment Emergent Adverse Events (TEAEs), Acute Phase Reaction (APRs) and Treatment Emergent Serious Adverse Events (TESAEs) and Suspected Unexpected Serious Adverse Events (SUSARs) during the Open Label Extension Study.
Time frame: Week 12
Endpoints will be summarized descriptively. Descriptive statistics for categorical variables will be frequencies and percentages. Descriptive statistics for continuous variables will be means, standard deviations, medians, minimums, and maximums.
19 secondary outcomes
Change in "average pain" from baseline
Time frame: Day 10, Weeks 3, 6, and 12
At least a 30%, 50%, 70%, and 90% reduction of "average pain" from baseline
Time frame: Day 10, Weeks 3, 6, and 12
Change from baseline in "pain now"
Time frame: Day 10, Weeks 3, 6, and 12
At least a 30%, 50%, 70%, and 90% reduction from baseline in "pain now"
Time frame: Day 10, Weeks 3, 6, and 12
Change from baseline in "worst pain"
Time frame: Week 12
At least a 30%, 50%, 70%, and 90% reduction from baseline of "worst pain"
Time frame: Day 10 and Weeks 3, 6, and 12
Change from baseline in the CRPS Severity Score (CSS)
Time frame: Day 10, Weeks 3, 6, and 12
Change from baseline to Week 12 in the CSS self-report (CSS-SR).
Time frame: Week 12
Change from baseline in edema of affected limb
Time frame: Day 10, Weeks 3, 6, and 12
Change from baseline in temperature (°C) of the affected limb vs contralateral limb.
Time frame: Day 10 and Weeks 3, 6, and 12
Patient Global Impression of Change (PGI-C) in CRPS-related health
Time frame: Day 10 and Weeks 3, 6, and 12
Clinician Global Impression of Change (CGI-C) in CRPS-related health
Time frame: Day 10 and Weeks 3, 6, and 12.
Change from baseline in Patient Global Impression of Severity (PGI-S) in CRPS Severity.
Time frame: Day 10 and Weeks 3, 6, and 12
Change from baseline in Short-Form McGill Pain Questionnaire 2 (SF-MPQ-2) (a) total pain score, (b) each of 4 domain scores, (c) single items.
Time frame: Day 10 and Weeks 3, 6, and 12
Moderate (at least 30%) and substantial (at least 50%) improvement from baseline in SF-MPQ-2 (a) total pain score, and (b) each of 4 domain scores.
Time frame: Day 10 and Weeks 3, 6, and 12
Change from baseline in the 36-item Short Form 36 Item Health Survey [SF-36] (a) 8 domain scores and (b) 2 component summary scores.
Time frame: Day 10 and Weeks 3, 6, and 12
Moderate (at least 30%) and substantial (at least 50%) improvement from baseline in the SF-36 (a) 8 domain scores and (b) 2 component summary scores.
Time frame: Day 10 and Weeks 3, 6, and 12
Change from baseline in the Daily Sleep Interference Scale (DSIS) assessment on an 11-point NRS.
Time frame: Day 10 and Weeks 3, 6, and 12
Moderate (at least 30%) and substantial (at least 50%) improvement from baseline in the DSIS assessment.
Time frame: Day 10 and Weeks 3, 6, and 12
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 16 Oct 2026.
- Trial websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Gail Cawkwell, MD, PhD study director
Ambros Therapeutics, Inc.
1 site 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 1 site 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 11 inclusion and 16 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 16 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 1 site 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. 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 Ambros Therapeutics (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?
Number of Participants with Treatment Emergent Adverse Events (TEAEs), Acute Phase Reaction (APRs) and Treatment Emergent Serious Adverse Events (TESAEs) and Suspected Unexpected Serious Adverse Events (SUSARs) during the Open Label Extension Study. (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 16 Oct 2026.