Evaluation of IV AMBTX-01 (Neridronate) for Treatment of CRPS Type 1 (CRPS-RISE)

Phase 3Not Yet RecruitingNCT07210515

Ambros Therapeutics, Inc.270 enrolled

Overview

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: * Screening period of up to 6 weeks * Treatment period on Days 1, 4, 7, and 10 * Post-treatment follow-up through week 12

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

270

Conditions

Complex Regional Pain Syndrome Type I

Interventions

NeridronateDRUG

neridronate 100 mg, given as a 2-hour infusion on Days 1, 4, 7, and 10.

PlaceboDRUG

placebo comparator

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: Week 12

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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."

Time frame: 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.

Time frame: 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.

Central Contacts

SVP, Clinical Operations

CONTACT

+1 949-785-4954 clinicaltrials@ambrostx.com

Ambros Therapeutics, Inc

CONTACT

Data from ClinicalTrials.gov

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Time frame: 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.

Time frame: Days 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.

Time frame: 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, based on the 7-day average of twice-daily "pain now" ratings 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.

Time frame: 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.

Time frame: 7-day average

Change from baseline in the 7-day average of the twice-daily "worst possible pain" assessments.

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

Time frame: 7-day average

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.

Time frame: Day 10, Weeks 3, 6, 9, and 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.

Time frame: Days 4, 7, 10, Weeks 3, 6, 9, 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.

Time frame: Days 4, 7, 10, Weeks 3, 6, 9, and 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.

Time frame: Days 4, 7, 10, Weeks 3, 6, 9, and 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).

Time frame: Days 4, 7, 10, Weeks 3, 6, and 9

Change from baseline 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.

Time frame: Days 4, 7, 10, Weeks 3, 6, 9, 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.

Time frame: Days 4, 7, 10, Weeks 3, 6, 9, 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).

Time frame: 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.

Time frame: 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 ≥ 15 mg oxycodone \> 3 days/week during the 7 days before the given study visit.

Time frame: 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.

Time frame: Days 4, 7, 10, Weeks 3, 6, 9, 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, and 5, respectively.

Time frame: Days 4, 7, 10, Weeks 3, 6, 9, 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.

Time frame: Days 4, 7, 10, Weeks 3, 6, 9, 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.

Time frame: Days 4, 7, 10, and Weeks 3, 6, 9, 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, 9, 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

Time frame: Days 4, 7, 10, Weeks 3, 6, 9, and 12

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, 9, 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.

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