CHronic Nonbacterial Osteomyelitis International Registry

NCT04725422 | Recruiting

• 1 other identifier: 1232
• Study Type: observational
• Target: 2,000
• Locations: 1 country
• Sites: 1

Brief Summary

The objective of the study is to establish a prospective disease registry for chronic recurrent multifocal osteomyelitis (CRMO)/chronic nonbacterial osteomyelitis (CNO) in order to investigate the natural history of the disease and the responses of patients to different clinical managements over 10 years.

Conditions

Chronic Nonbacterial Osteomyelitis; Chronic Recurrent Multifocal Osteomyelitis

Outcome Measures

Primary Outcomes (1)

• The change of CNO disease activity score

  Disease activity score is calculated as the sum of number of clinical lesion count, patient global assessment (0-10), physician global assessment (0-10)

  3-6 months

Secondary Outcomes (2)

• Total number of CNO lesions on MRI

  3-6 months

• Safety monitoring

  5 years

Study Arms (4)

disease modifying anti-rheumatic drug, DMARD

1. Methotrexate 1 mg/kg (max 25 mg) PO or SQ weekly 2. Sulfasalazine 30 mg/kg (max 1000 mg) PO twice daily 3. Leflunomide 10-20 mg PO daily

Drug: Methotrexate; Drug: Sulfasalazine; Drug: Leflunomide

tumor necrosis factor inhibitor, TNFi

1. Adalimumab (subcutaneous) 10-40 mg SQ every other week 2. Etanercept (subcutaneous) 12.5-50 mg SQ every week 3. Infliximab (intravenous) 10 mg/kg (max 1000 mg) i.v. at week 0,2, 6 then every 4 weeks 4. Golimumab (subcutaneous or intravenous) 2 mg/kg (max 200 mg) at every 4 weeks

Drug: Etanercept; Drug: Adalimumab; Drug: Certolizumab; Drug: Infliximab; Drug: Golimumab

bisphosphonate

1. Pamidronate 1 mg/kg (max 90 mg) (intravenous)\*: Option 1: every month Option 2: 3 consecutive days every 3 months 2. Zoledronic acid 0.0125-0.05 mg/kg (max 4mg) (intravenous): every 3-6 months. \* Both options may use lower dose of 0.5 mg/kg at the initiation of the treatment. All options allow concurrent use of NSAIDs.

Drug: Pamidronate; Drug: Zoledronic acid

non-steroidal anti-inflammatory drugs

1. Naproxen 10 mg/kg (max 500 mg) PO twice daily 2. Indomethacin 1 mg/kg (max daily dose 150 mg) PO twice or three times daily 3. Meloxicam 0.1-0.3 mg/kg (max 15 mg) PO daily 4. Piroxicam 10-20 mg PO daily 5. Ibuprofen 10 mg/kg (max 800 mg) PO 3-4 times daily

Drug: NSAID

Interventions

Methotrexate DRUG

second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs

disease modifying anti-rheumatic drug, DMARD

Sulfasalazine DRUG

second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs

Also known as: Azulfidine

disease modifying anti-rheumatic drug, DMARD

Leflunomide DRUG

second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs

Also known as: areva

disease modifying anti-rheumatic drug, DMARD

Pamidronate DRUG

second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs

Also known as: Aredia

bisphosphonate

Zoledronic acid DRUG

second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs

bisphosphonate

Etanercept DRUG

second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs

Also known as: enbrel

tumor necrosis factor inhibitor, TNFi

Adalimumab DRUG

second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs

Also known as: humira

tumor necrosis factor inhibitor, TNFi

Certolizumab DRUG

second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs

Also known as: cimzia

tumor necrosis factor inhibitor, TNFi

Infliximab DRUG

second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs

Also known as: remicade, inflectra

tumor necrosis factor inhibitor, TNFi

Golimumab DRUG

second-line treatment for children with CNO/CRMO after failure to respond to NSAIDs

Also known as: simponi

tumor necrosis factor inhibitor, TNFi

NSAID DRUG

first-line treatment

non-steroidal anti-inflammatory drugs

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Children with a diagnosis of CNO/CRMO who have failed NSAIDs and/or with active spinal lesion

You may qualify if:

• \- Age at enrollment is equal to or younger than 21 years of age
• Presence of bone edema on STIR or T2 fat saturation sequence on MRI within 12 weeks of enrollment
• Whole body imaging evaluation (either WB MRI or bone scintigraphy)
• Bone biopsy to exclude infection or malignancy unless bone lesions follow typical distribution or there is IBD, psoriasis, or palmar plantar pustulosis

You may not qualify if:

• \- History of or current malignancy
• Current infectious osteomyelitis
• Contraindication to the selected treatment agent

Sponsors & Collaborators

• Seattle Children's Hospital: lead
• Boston Children's Hospital, Boston, MA, USA: collaborator
• Hospital for Special Surgery, New York: collaborator
• Joseph M Sanzari Children's Hospital, Hackensack University Medical Center, Hackensack, NJ, USA: collaborator
• Riley Children's Hospital, Indianapolis, IN, USA: collaborator
• University of North Carolina, Chapel Hill, NC, USA: collaborator
• Royal Children's Hospital: collaborator
• Hacettepe University: collaborator
• Bambino Gesù Children's Hospital, Rome, Italy: collaborator
• University of British Columbia, Vancouver, BC, Canada: collaborator
• Meyer Children's Hospital, Florence, Italy: collaborator
• Mansoura University: collaborator
• University of Utah, Salt Lake City, UT, USA: collaborator
• University of Iowa Carver College of Medicine, Iowa City, IA, USA: collaborator
• Ann & Robert Lurie Children's Hospital of Chicago, Chicago, IL, USA: collaborator
• Palacky University Olomouc Institute of Molecular and Translational Medicine, Olomouc, Czechia: collaborator
• Alder Hey Children's NHS Foundation Trust Hospital, Liverpool, UK: collaborator
• University of Calgary, Calgary, Alberta, Canada: collaborator

Study Sites (1)

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

Related Publications (7)

• Zhao Y, Wu EY, Oliver MS, Cooper AM, Basiaga ML, Vora SS, Lee TC, Fox E, Amarilyo G, Stern SM, Dvergsten JA, Haines KA, Rouster-Stevens KA, Onel KB, Cherian J, Hausmann JS, Miettunen P, Cellucci T, Nuruzzaman F, Taneja A, Barron KS, Hollander MC, Lapidus SK, Li SC, Ozen S, Girschick H, Laxer RM, Dedeoglu F, Hedrich CM, Ferguson PJ; Chronic Nonbacterial Osteomyelitis/Chronic Recurrent Multifocal Osteomyelitis Study Group and the Childhood Arthritis and Rheumatology Research Alliance Scleroderma, Vasculitis, Autoinflammatory and Rare Diseases Subcommittee. Consensus Treatment Plans for Chronic Nonbacterial Osteomyelitis Refractory to Nonsteroidal Antiinflammatory Drugs and/or With Active Spinal Lesions. Arthritis Care Res (Hoboken). 2018 Aug;70(8):1228-1237. doi: 10.1002/acr.23462. Epub 2018 Jul 12.

  PMID: 29112802 BACKGROUND

• Zhao Y, Ferguson PJ. Chronic Nonbacterial Osteomyelitis and Chronic Recurrent Multifocal Osteomyelitis in Children. Pediatr Clin North Am. 2018 Aug;65(4):783-800. doi: 10.1016/j.pcl.2018.04.003.

  PMID: 30031498 BACKGROUND

• Oliver M, Lee TC, Halpern-Felsher B, Murray E, Schwartz R, Zhao Y; CARRA SVARD CRMO/CNO workgroup. Disease burden and social impact of pediatric chronic nonbacterial osteomyelitis from the patient and family perspective. Pediatr Rheumatol Online J. 2018 Dec 14;16(1):78. doi: 10.1186/s12969-018-0294-1.

  PMID: 30547806 BACKGROUND

• Beck C, Morbach H, Beer M, Stenzel M, Tappe D, Gattenlohner S, Hofmann U, Raab P, Girschick HJ. Chronic nonbacterial osteomyelitis in childhood: prospective follow-up during the first year of anti-inflammatory treatment. Arthritis Res Ther. 2010;12(2):R74. doi: 10.1186/ar2992.

  PMID: 20433730 BACKGROUND

• Girschick H, Finetti M, Orlando F, Schalm S, Insalaco A, Ganser G, Nielsen S, Herlin T, Kone-Paut I, Martino S, Cattalini M, Anton J, Mohammed Al-Mayouf S, Hofer M, Quartier P, Boros C, Kuemmerle-Deschner J, Pires Marafon D, Alessio M, Schwarz T, Ruperto N, Martini A, Jansson A, Gattorno M; Paediatric Rheumatology International Trials Organisation (PRINTO) and the Eurofever registry. The multifaceted presentation of chronic recurrent multifocal osteomyelitis: a series of 486 cases from the Eurofever international registry. Rheumatology (Oxford). 2018 Jul 1;57(7):1203-1211. doi: 10.1093/rheumatology/key058.

  PMID: 29596638 BACKGROUND

• Voit AM, Arnoldi AP, Douis H, Bleisteiner F, Jansson MK, Reiser MF, Weckbach S, Jansson AF. Whole-body Magnetic Resonance Imaging in Chronic Recurrent Multifocal Osteomyelitis: Clinical Longterm Assessment May Underestimate Activity. J Rheumatol. 2015 Aug;42(8):1455-62. doi: 10.3899/jrheum.141026. Epub 2015 May 15.

  PMID: 25979713 BACKGROUND

• Wu EY, Oliver M, Scheck J, Lapidus S, Akca UK, Yasin S, Stern SM, Insalaco A, Pardeo M, Simonini G, Marrani E, Wang X, Huang B, Kovalick LK, Rosenwasser N, Casselman G, Liau A, Shao Y, Yang C, Mosa DM, Tucker L, Girschick H, Laxer RM, Akikusa JD, Hedrich CM, Onel K, Dedeoglu F, Twilt M, Ferguson PJ, Ozen S, Zhao Y. Feasibility of Conducting Comparative Effectiveness Research and Validation of a Clinical Disease Activity Score for Chronic Nonbacterial Osteomyelitis. J Rheumatol. 2023 Oct;50(10):1333-1340. doi: 10.3899/jrheum.2022-1323. Epub 2023 Jul 1.

  PMID: 37399459 BACKGROUND

MeSH Terms

Conditions

Chronic recurrent multifocal osteomyelitis

Interventions

Methotrexate; Sulfasalazine; Leflunomide; Pamidronate; Zoledronic Acid; Etanercept; Adalimumab; Certolizumab Pegol; Infliximab; golimumab; Anti-Inflammatory Agents, Non-Steroidal

Intervention Hierarchy (Ancestors)

Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Diphosphonates; Organophosphonates; Organophosphorus Compounds; Imidazoles; Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Polyethylene Glycols; Polymers; Macromolecular Substances; Immunoglobulin Fab Fragments; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Anti-Inflammatory Agents; Therapeutic Uses; Antirheumatic Agents

Central Study Contacts

Yongdong (Dan) Zhao, MD, PhD

CONTACT

206-987-2000; crmoresearch@seattlechildrens.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle Investigator

Study Record Dates

• First Submitted: January 18, 2021
• First Posted: January 26, 2021
• Study Start: August 1, 2018
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2050
• Last Updated: July 30, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)