Efficacy and safety of intravenous neridronic acid in CRPS

Phase 1

• Conditions: Complex Regional Pain Syndrome (CRPS).; MedDRA version: 20.1 Level: LLT Classification code 10064334 Term: Complex regional pain syndrome Type I System Organ Class: 100000004852; MedDRA version: 20.1 Level: LLT Classification code 10064335 Term: Complex regional pain syndrome Type II System Organ Class: 100000004852; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2016-003833-91-ES
• Lead Sponsor: Grünenthal GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-08-10
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 360

Inclusion Criteria

1. Informed consent signed.
2. Male or female subjects at least 18 years of age at Visit 1.
3. A diagnosis of CRPS according to the clinical diagnostic criteria recommended by the International Association for the Study of Pain (IASP; Budapest clinical criteria”), assessed at Visit 1. Signs and symptoms of CRPS must apply to an affected limb (arm or leg) and must demonstrate asymmetry with respect to the contralateral limb. The CRPS duration must be 2 years or less since onset of symptoms.
4. A baseline average pain intensity score of greater than or equal to 4 using an 11-point NRS, referring to the CRPS-affected limb (average of pain recorded over 7 days). The baseline average pain intensity score will be calculated automatically by the electronic diary, which must be checked prior to allocation at Visit 2. A subject who has not met average baseline pain intensity requirements (at least 4 average pain intensity ratings) due to lack of compliance with the electronic diary may be rescheduled for Visit 2 (1 time only), with appropriate re-training to ensure compliance with use of the electronic diary.
5. In stable treatment and follow-up therapy for CRPS for at least 1 month prior to allocation to treatment (Visit 2). Subjects must have failed attempts with at least 2 available treatments for CRPS, 1 of which must have been a pharmacologic treatment.
6. Women of child-bearing potential must have a negative urine ß-HCG pregnancy test at Visit 1 and must be using 2 forms of medically acceptable contraception, including at least 1 highly effective method of contraception with a low failure rate, defined as less than 1% per year (e.g., oral contraceptives or intrauterine device), and a second medically acceptable method such as use of condoms with spermicide by their male partner. A barrier method alone is not acceptable. Highly effective methods of contraception must be used for at least 1 month prior to Visit 2 and for the duration of the trial. Male subjects must use condom and spermicide during intercourse and must take care that the female sexual partner uses at least 1 additional method of contraception with a low failure rate defined as above, starting with Visit 2 until at least 4 weeks after the last IMP infusion.
7. Subjects must be able to communicate meaningfully, be able to differentiate with regard to location and intensity of the pain, and be able to answer the questions in the questionnaires used in this trial (assistance in filling out the questionnaires may be provided, if required due to motor or other physical impairment).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 324
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 36

Exclusion Criteria

1. Evidence of renal impairment (estimated glomerular filtration rate [eGFR] less than 30 mL/min/1.73 m2 using the 2009 Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] creatinine equation [Levey et al. 2009] or a urinary albumin to creatinine ratio [ACR] greater than 150 mg/g), based on central safety laboratory data obtained prior to Visit 2.
2. Serum calcium or magnesium outside of the central laboratory’s reference range, based on central safety laboratory data obtained prior to Visit 2; a history of hypocalcemia or a metabolic disorder anticipated to increase risk for hypocalcemia; anticipated need for any new drug with known potential to cause hypocalcemia during the trial.
3. Vitamin D deficiency, defined as a 25(OH)D level less than 30 ng/mL (75 nmol/L), based on central safety laboratory data obtained prior to Visit 2. Subjects with vitamin D deficiency should receive appropriate supplementation during the Enrollment Period. A vitamin D level of at least 30 ng/mL (75 nmol/L) must be documented prior to allocation to IMP.
4. Corrected QT interval (according to Fridericia’s formula; QTcF) greater than 470 ms (average of 3 ECGs obtained at Visit 1) according to central ECG reading facility evaluation or QTcF greater than 470 ms at pre-dose ECG at Visit 2 according to the investigator’s judgment; serum potassium outside the central laboratory’s reference range at Visit 1; clinically unstable cardiac disease.
5. Subjects receiving medications with a known risk of torsades de pointes within 7 days prior to allocation. Subjects receiving selective serotonin re-uptake inhibitor antidepressants are eligible if the QT interval values do not meet the exclusion criteria, the medication was started at least 1 month prior to allocation, the dose is stable, and the dose is anticipated to remain stable throughout the trial.
6. Any prior use of a bisphosphonate for treatment of CRPS, any prior administration of a bisphosphonate within the previous year, anticipated requirement for treatment with a bisphosphonate for another condition such as osteoporosis during the trial, or administration of denosumab (Prolia®) or other bone turnover suppressing drugs within 6 months prior to Visit 1.
7. History of any allergic or hypersensitivity reaction to neridronic acid or other bisphosphonate, acetaminophen, or to vitamin D or calcium supplements.
8. Recent tooth extraction or other invasive dental procedure (within 3 months prior to Visit 1), unhealed or infected extraction site, or significant dental/periodontal disease that may pre-dispose to need for tooth extraction or other invasive dental procedures during the trial. Subjects with indeterminate, suspicious or unreliable dental history, in the opinion of the investigator, must undergo a dental examination prior to receiving treatment.
9. Evidence of denture-related gum trauma or improperly fitting dentures causing injury.
10. Prior radiation therapy of the head or neck (within 1 year of Visit 1).
11. History of malignancy within 2 years prior to Visit 1, with the exception of basal cell carcinoma.
12. Nerve blocks, ketamine infusions, intravenous immunoglobulin, acupuncture, electromagnetic field treatment, or initiation/implementation of radiofrequency ablation or other sympathectomy p

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified