IV neridronate for warm-type Complex Regional Pain Syndrome (CRPS-1) with a positive bone scan

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)

This trial will try IV neridronate to reduce pain and swelling in adults with recent-onset warm-subtype CRPS-1 who have a positive triple-phase bone scan.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 270 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ambros Therapeutics, Inc. (industry)
• Locations: 6 sites (Phoenix, Arizona and 5 other locations)
• Trial ID: NCT07210515 on ClinicalTrials.gov

What this trial studies

This multicenter, randomized, triple-blind, placebo-controlled Phase 3 trial gives 400 mg IV neridronate on Days 1, 4, 7, and 10 to adults with the warm subtype of CRPS-1 and a positive triple-phase bone scan. Eligible participants have a single affected limb, CRPS symptoms for six months or less, and meet Budapest clinical criteria without known peripheral nerve injury. Each participant will be in the program for up to about 18 weeks including up to 6 weeks of screening and follow-up through Week 12. The trial compares neridronate against placebo for effects on pain, edema, function, and safety.

Who should consider this trial

Good fit: Adults aged 18 or older with a single-limb, warm-subtype CRPS-1 of six months or less, a positive triple-phase bone scan, and no known peripheral nerve injury are the ideal candidates.

Not a fit: Patients with chronic (>6 months) or cold-subtype CRPS, multiple affected limbs, documented peripheral nerve injury, a negative bone scan, children, or those unable to receive IV infusions are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, neridronate could reduce pain and swelling and improve limb function in people with early warm-type CRPS-1.

How similar studies have performed: Smaller randomized trials of neridronate and other IV bisphosphonates have reported benefits in CRPS, but large confirmatory phase 3 data have been limited.

Eligibility criteria

Inclusion Criteria:

1. Male or female participant ≥ 18 years of age at time of Screening.
2. 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.
3. Single affected limb at the Screening and Randomization Visits meeting the following warm subtype criteria:

   1. Edema in the affected limb
   2. AND ≥ 2 of the following:

      1. Obvious redness in the affected region relative to the same region on the contralateral limb on inspection
      2. ≥ 1°C increase in temperature on the affected limb relative to the contralateral limb
      3. Moderate-to-severe edema
4. CRPS symptoms ≤ 6 months since onset.
5. 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.
6. "Pain now" assessments of \> 4 on the 11 point numerical rating scale in the CRPS affected limb.
7. Women of childbearing potential must:

   1. Be nonpregnant.
   2. Be nonlactating.
   3. 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.

Exclusion Criteria

1. 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.
2. ≥ 40 points on the Pain Catastrophizing Scale.
3. Prior use of neridronate or participation in a clinical study where the participant may have received neridronate.
4. 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.
5. Severely impaired renal function.
6. Hypocalcemia.
7. Vitamin D deficiency.
8. Significant dental findings such as an unhealed tooth extraction site.
9. Eye inflammation.
10. Significantly elevated liver-related lab tests or evidence of significant liver disease.
11. Clinically unstable cardiac disease.
12. 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.

Where this trial is running

Phoenix, Arizona and 5 other locations

• Ambros Clinical Trial Site — Phoenix, Arizona, United States (RECRUITING)
• Ambros Clinical Trial Site — Tucson, Arizona, United States (RECRUITING)
• Ambros Clinical Trial Site — Tustin, California, United States (RECRUITING)
• Ambros Clinical Trial Site — Pembroke Pines, Florida, United States (RECRUITING)
• Ambros Clinical Trial Site — Newnan, Georgia, United States (RECRUITING)
• Ambros Clinical Trial Site — Winston-Salem, North Carolina, United States (RECRUITING)

Study contacts

• Study coordinator: SVP, Clinical Operations

Conditions: Complex Regional Pain Syndrome Type I, CRPS, edema, pain, RDS