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Complex Regional Pain SyndromePhase 3NCT02972359

Safety of Intravenous Neridronic Acid in CRPS

A Phase 3 study testing Neridronic acid in people with Complex Regional Pain Syndrome, run by Grünenthal GmbH at 46 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The aim of this trial was to investigate the safety of intravenous neridronic acid in patients with complex regional pain syndrome (CRPS). The trial was divided into 3 periods: a 60-day enrollment period, a treatment period consisting of 4 infusions over 10 days, and a follow-up period of approximately 50 weeks (with… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Complex Regional Pain Syndrome
What is being tested?
Neridronic acid
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
580 participants
Where
46 sitesin 2 countries
Study dates
20 Dec 2016to 9 Jan 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Informed consent signed.
  • Male or female participant at least 18 years of age at Visit 1.
  • A diagnosis of complex regional pain syndrome 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.
  • Ongoing moderate to severe chronic pain, including a baseline current pain intensity score of greater than or equal to 4 using an 11-point Numerical Rating Scale, referring to the CRPS-affected limb, at Visit 2 (prior to dosing).
  • In stable treatment and follow-up therapy for CRPS for at least 1 month prior to allocation to treatment (Visit 2). Participants must have failed trials of at least 2 treatments for CRPS, one of which must be a pharmacologic treatment.
  • Women of child-bearing potential must have a negative urine beta-human chorionic gonadotropin (β-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.
  • Participants 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 impairment).

Who cannot join

  • Evidence of renal impairment (estimated glomerular filtration rate [eGFR] less than 60 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 creatinine ratio greater than 150 mg/g), based on central safety laboratory data obtained prior to Visit 2, or a history of chronic kidney disease. Note: a single repeat laboratory test is allowed.
  • Serum calcium or magnesium outside of the central laboratory's reference range, based on central safety laboratory data obtained prior to Visit 2 (a single repeat laboratory test is allowed); a history of hypocalcemia or a metabolic disorder anticipated to increase risk for hypocalcemia (e.g., hypoparathyroidism); concomitant use of drug(s) with known potential to cause hypocalcemia (e.g., aminoglycosides).
  • Vitamin D deficiency, defined as a 25(OH)D level less than 30 ng/mL, based on central safety laboratory data obtained prior to Visit 2 (up to 4 repeat laboratory tests are allowed). Participants with vitamin D deficiency should receive appropriate supplementation during the enrollment period. A vitamin D level of at least 30 ng/mL must be documented prior to allocation to investigational medicinal product (IMP).
  • Corrected QT interval (according to Fridericia's formula; QTcF) greater than 470 ms (average of 3 electrocardiograms [ECGs] obtained at Visit 1); serum potassium outside the central laboratory's reference range at Visit 1; clinically unstable cardiac disease, including: unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, active myocardial ischemia, or an indwelling pacemaker; evidence of complete left bundle branch block; complete atrioventricular block; history of Long QT Syndrome or a relative with this condition; or any other known risk factor for torsade de pointes.
  • Participants receiving medications with a known risk of torsades de pointes within 7 days prior to allocation. Participants receiving selective serotonin re-uptake inhibitor antidepressants (e.g., citalopram, escitalopram) or tricyclic 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 until at least 4 days after the last infusion of IMP.
  • Anticipated requirement for treatment with oral or intravenous bisphosphonate for another condition such as osteoporosis during the trial, or administration of denosumab (Prolia®) or other drugs affecting bone turnover or bone metabolism within 6 months prior to Visit 1.
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  • History of any allergic or hypersensitivity reaction to neridronic acid or other bisphosphonate, acetaminophen, or to vitamin D or calcium supplements.
  • 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 (e.g., impacted molars, severe tooth decay, foci of infection) that may predispose to need for tooth extraction or other invasive dental procedures during the trial. Participants with indeterminate, suspicious or unreliable dental history, in the opinion of the investigator, must undergo a dental examination prior to receiving treatment.
  • Evidence of denture-related gum trauma or improperly fitting dentures causing injury.
  • Prior radiation therapy of the head or neck (within 1 year of Visit 1).
  • History of malignancy within 2 years prior to Visit 1, with the exception of basal cell carcinoma.
  • Use of nerve blocks, ketamine infusions, intravenous immunoglobulin, acupuncture, electromagnetic field treatment, or initiation/implementation of radiofrequency ablation or other sympathectomy procedures, or peripheral nerve stimulation within 6 weeks prior to Visit 2.
  • Evidence of current alcohol or drug abuse, or history of alcohol or drug abuse within 2 years of Visit 1, based on participant history and physical examination and according to the investigator's judgment.
  • Any other severe medical condition, including severe depression, or any other severe mood disorder, that in the opinion of the investigator may affect efficacy or safety assessments or may compromise the participant's safety during trial participation.
  • Women who are pregnant or breastfeeding.
  • Elevated aspartate aminotransferase or alanine aminotransferase greater than 2-fold upper limit of normal, based on central safety laboratory data obtained at Visit 1, or current evidence of chronic liver disease. Safety laboratory testing may be repeated prior to Visit 2, and participants will be allowed in the trial if results of 2 consecutive tests, at least 3 days apart, are less than or equal to 2-fold upper limit of normal.
  • Participation in another investigational drug trial within 3 months prior to Visit 1 or any previous trial with neridronic acid, with the exception of participants of KF7013-01 who were assigned to placebo and did not receive neridronic acid.
  • Participant is engaged in litigation related to their disability from CRPS in which monetary gain or loss (or other compensation) may affect their objective participation in the trial.
  • Participants taking forbidden concomitant medications/therapies or not being able to follow the rules of use of concomitant treatment.
  • Participants incapable of signing the informed consent.

Trial locations and contacts

46 sites in 2 countries.

46 sites in 2 countries

United States42 sites

  • US048: Albany Medical College

    Albany, New York, 12208

  • US012: Orange County Research Institute

    Anaheim, California, 92801

  • US019: Austin Center for Clinical Research

    Austin, Texas, 78758

  • US018: Washington Center for Pain Management

    Bellevue, Washington, 98004

  • US015: Northwest Clinical Research Center

    Bellevue, Washington, 98007

  • US022: Core Healthcare Group

    Cerritos, California, 90703

  • US020: Clinical Trials of South Carolina

    Charleston, South Carolina, 29406

  • US004: Northwestern University - Feinberg School of Medicine - Rehabilitation Institute of Chicago (RIC)

    Chicago, Illinois, 60611

  • US036: University Anesthesiologists, S.C.

    Chicago, Illinois, 60612

  • US029: Great Lakes Clinical Trials LLC

    Chicago, Illinois, 60640

  • US032: South Lake Pain Institute

    Clermont, Florida, 34711

  • US034: Mountain View Clinical Research, Inc.

    Denver, Colorado, 80209

  • US008: Pioneer Research Solutions

    Houston, Texas, 77099

  • US033: Alliance Research Centers

    Laguna Hills, California, 92653

  • US027: The Helm Center for Pain Management

    Laguna Woods, California, 92637

  • US045: Woodland International Research Group

    Little Rock, Arkansas, 72211

  • US003: Samaritan Center for Medical Research

    Los Gatos, California, 95032

  • US001: Sunrise Research Institute, Inc

    Miami, Florida, 33130

  • US046: AMPM Research Clinic

    Miami, Florida, 33169

  • US016: North Star Medical Research, LLC

    Middleburg Heights, Ohio, 44130

  • US010: Catalina Research Institute, LLC

    Montclair, California, 91763

  • US038: Vanderbilt University Medical Center

    Nashville, Tennessee, 37212-1050

  • US026: Better Health Clinical Research Inc.

    Newnan, Georgia, 30265

  • US007: Medical Research International

    Oklahoma City, Oklahoma, 73109-4520

  • US051: Creighton University, Osteoporosis Research Center

    Omaha, Nebraska, 68122

  • US035: Compass Research

    Orlando, Florida, 32806

  • US005: International Clinical Research Institute

    Overland Park, Kansas, 66210

  • US017: Cactus Clinical Research, Inc.

    Phoenix, Arizona, 85012

  • US031: Gold Coast Research, LLC

    Plantation, Florida, 33317

  • US002: Princeton Medical Institute

    Princeton, New Jersey, 08540

  • US043: Translational Pain Research, University of Rochester

    Rochester, New York, 14618

  • US044: Woodland Research Northwest

    Rogers, Arkansas, 72758

  • US014: Northern California Research

    Sacramento, California, 95821

  • US023: Axios Research, LLC

    Salt Lake City, Utah, 84106

  • US013: Swedish Pain Services/ Research Institute

    Seattle, Washington, 98122

  • US049: Premier Pain Centers, LLC

    Shrewsbury, New Jersey, 07702

  • US037: St. Louis Clinical Trials, LC

    St Louis, Missouri, 63141

  • US011: Clinical Research of West Florida, Inc.

    Tampa, Florida, 33603

  • US028: Quality of Life Medical and Research Centers LLC

    Tucson, Arizona, 85712

  • US040: Palm Beach Research Center

    West Palm Beach, Florida, 33409

  • US006: Abington Neurological Associates, LTD.

    Willow Grove, Pennsylvania, 19090

  • US009: The Center for Clinical Research, LLC

    Winston-Salem, North Carolina, 27103

Other trials in United States

Germany4 sites

  • DE001: Klinische Forschung Hannover-Mitte GmbH

    Hanover, 30159

  • DE004: Schmerzambulanz Medizinishe Hochschule Hannover

    Hanover, 30625

  • DE006: AmBeNet GmbH

    Leipzig, 04107

  • DE002: Schmerztagesklinik der Anästhesiologie Universitätsklinikum Würzburg

    Würzburg, 97080

Other trials in Germany

About this study

Official title: Open-label Safety Trial of Intravenous Neridronic Acid in Subjects With Complex Regional Pain Syndrome (CRPS)

The aim of this trial was to investigate the safety of intravenous neridronic acid in patients with complex regional pain syndrome (CRPS).

The trial was divided into 3 periods: a 60-day enrollment period, a treatment period consisting of 4 infusions over 10 days, and a follow-up period of approximately 50 weeks (with visits at Week 2, Week 6, Week 12, Week 26, Week 39, and Week 52).

Read the detailed description

At the Enrollment Visit the trial objectives, procedures, and risks were explained to the participants and the informed consent form was signed. Medical history was obtained, a physical examination was conducted, and other safety assessments were performed. Signs and symptoms of CRPS were assessed to confirm the diagnosis of CRPS according to the Budapest clinical criteria. Participants were trained to report their pain. Calcium and vitamin D supplementation were initiated to ensure sufficient vitamin D levels prior to treatment.

Participants meeting all eligibility criteria received infusions of investigational medicinal product (IMP) during visits on Day 1, Day 4, Day 7, and Day 10. Flexibility of ±1 day was allowed for Day 4, Day 7, and Day 10 whilst ensuring a minimum period of 48 hours between infusions. During the treatment period and follow-up period, pain intensity ratings were captured at the site visits in a patient reported-outcome system.

Being tested
Neridronic acid
Keywords
Neridronic Acid, Neridronate, CRPS, RSD (reflex sympathetic dystrophy)
Medical subject headings
Complex Regional Pain Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Neridronic acidDrug

    Neridronic acid administered as intravenous infusion.

Study groups in NCT02972359
Study groupRoleWhat they receive
Neridronic acidExperimentalNeridronic acid 100 mg administered on Day 1, Day 4, Day 7, and Day 10, resulting in a total dose of neridronic acid 400 mg.
Receives: Drug: Neridronic acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Occurrence of Any Treatment Emergent Adverse Event (TEAE)

    The primary endpoint of this trial was a binary endpoint assessing whether or not a participant experienced any TEAE.

    Measured: Day 1 to Week 52

Secondary outcomes (7)

  1. Number of Participants With Occurrence of Permanent Discontinuation From Treatment Due to an Adverse Event

    The investigator could choose to permanently discontinue a participant from treatment if continued exposure of the participant to neridronic acid could have posed an undue risk to the participant.

    Measured: Day 1 to Day 10

  2. Change From Baseline in the Current Pain Intensity Score

    The current Complex Regional Pain Syndrome (CRPS)-related pain intensity score was captured at each visit using an 11-point numerical rating scale where 0 = "no pain" and 10 = "pain as bad as you can imagine", a higher score indicates more pain.

    Measured: Baseline to Week 12 and Week 26

  3. Number of Participants With Response to Treatment, Defined as at Least 30% Decrease From Baseline in the Current Pain Intensity Score

    Participants with at least a 30 percent decrease in the current pain intensity score were considered to have responded to treatment.

    Measured: Baseline, at Week 12 and Week 26

  4. Number of Participants With Response to Treatment, Defined as at Least 50% Decrease From Baseline in the Current Pain Intensity Score

    Participants with at least a 50 percent decrease in the current pain intensity score were considered to have responded to treatment.

    Measured: Baseline, at Week 12 and Week 26

  5. Patient Global Impression of Change (PGIC) at Week 12

    The Patient Global Impression of Change (PGIC) is a self-reported measure of perceived change in overall condition since the start of the study. Participants selected one of seven responses ranging from "very much improved" to "very much worse". A response of "very much improved" or "much improved" is generally regarded as a clinically important improvement.

    Measured: at Week 12

  6. Patient Global Impression of Change (PGIC) at Week 26

    The Patient Global Impression of Change (PGIC) is a self-reported measure of perceived change in overall condition since the start of the study. Participants selected one of seven responses ranging from "very much improved" to "very much worse". A response of "very much improved" or "much improved" is generally regarded as a clinically important improvement.

    Measured: at Week 26

  7. Change in the Pain Interference Score of the Brief Pain Inventory (BPI)

    The Brief Pain Inventory (BPI) Interference Score is the mean value of 7 self-reported items in question 9 of the BPI Short Form Questionnaire. Participants rated their interference of pain with general activity, walking, work, sleep and other activities in the past 24 hours, with possible ratings from 0 (does not interfere) to 10 (completely interferes). The BPI interference Score ranges from 0 to 10, with higher values indicating greater pain interference of daily activities.

    Measured: Baseline to Week 12 and Week 26

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Nov 2016 (estimated)
  2. Study start20 Dec 2016
  3. Primary completion9 Jan 2019
  4. Study completion9 Jan 2019

Resources

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
580 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02972359
Sponsor's protocol ID
KF7013-03
Other IDs
2016-001164-11, U1111-1180-8099, 2016
Status last verified
Nov 2019
First submitted
21 Nov 2016
Last updated
21 Nov 2019
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Information available on the Grünenthal Web Site

Publications

  • Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009 May 5;150(9):604-12. doi: 10.7326/0003-4819-150-9-200905050-00006.

    PubMed 19414839

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Neridronic acid in people with Complex Regional Pain Syndrome, run by Grünenthal GmbH at 46 sites in 2 countries.

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 7 inclusion and 20 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: finished, as of the sponsor's last update on 21 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 46 sites in United States, Germany. 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?

Yes. Results are posted in the registry (first posted 4 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Occurrence of Any Treatment Emergent Adverse Event (TEAE) (time frame: Day 1 to Week 52). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02972359, which also lists 1 linked publication.

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 21 Nov 2019.

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