EFFICACY AND SAFETY OF ZOLEDRONATE VERSUS PLACEBO ON PAIN AT WEEK 12 IN PEDIATRIC PATIENTS WITH CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS

NCT07668583 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: APHP2207952023-506420-93-00
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare auto-inflammatory bone disease that primarily affects children and/or adolescents at a median age of 10 years. Until now, there is no consensus regarding the treatment of CRMO. Non-steroidal anti-inflammatory drugs (NSAIDs) are considered the first line of therapy with remission in approximately 30% of cases. If unsuccessful, several treatments are tried in addition to NSAIDs, including bisphosphonates and anti-TNFs. The effectiveness of bisphosphonates (including zoledronate) has been reported in clinical cases and/or retrospective series. They are said to be particularly effective in multifocal forms, mandibular and/or vertebral involvement, but no controlled trials have been conducted. Bisphosphonates have even been proposed as first-line therapy in spinal involvement. The only prospective study, is a phase II trial currently underway in Denmark to study the efficacy of zoledronate (NCT02594878) versus placebo in SAPHO (acronym, standing for Synovitis - Acne - Pustulosis - Hyperostosis - Osteitis) patients considered to be a very similar form of CRMO occurring in adults. In this context, this study proposes evaluate the efficacy of zoledronate compared to placebo in reducing pain at week 12 in children aged ≥4 and \<17 years with NSAID-resistant CRMO. Zoledronate will be administered in three escalating doses: 0.025 mg/kg at baseline (W0), 0.05 mg/kg at week 12 (W12), and 0.05 mg/kg at week 24 (W24). In addition to pain reduction, improvements in MRI findings will be observed, biological markers of inflammation, and quality of life in the zoledronate group. Although subjective, pain reduction remains the most widely used criterion in clinical practice to assess therapeutic efficacy. Zoledronate efficacy will therefore be assessed by the change in standardized pain score (0-10 scale) from baseline to week 12 as the primary endpoint, with additional pain assessments at weeks 4, 24, and 36 as secondary endpoints.

Conditions

Osteomyelitis Chronic

Keywords

Osteomyelitis

Outcome Measures

Primary Outcomes (1)

• Change in pain score from baseline to week 12

  Change in standardized pain score (0-10 scale) from baseline to week 12, using Visual Analog Scale VAS 0-10/ 0 = no pain ; 10 = worst imaginable pain

  week 12

Secondary Outcomes (14)

• Compare pain score (0-10 scale) evolution between groups at Weeks 4, 24 and 36

  Week 4, 24 and 36

• Use of NSAIDs, other analgesics and corticosteroids between the two groups during follow-up.

  Week 12, 24 and 36

• Clinical signs (Number of participants presenting clinical manifestations of CRMO (pain on palpation, arthritis, spinal deformity, extra-osseous manifestations, growth impairment and pubertal delay) between the two groups at baseline and follow-up visits

  Week 12, 24 and 36

• Biological inflammatory markers between the two groups at baseline and follow-up visits.

  Week 12, 24 and 36

• CNO Clinical Disease Activity Score (CNO CDAS)

  Week 12, 24 and 36

Study Arms (2)

Zoledronate

EXPERIMENTAL

Zoledronic acid, perfusion IV Baseline : 0.025 mg/kg ; Week 12 : 0.05 mg/kg ; Week 24 : 0.05 mg/kg

Drug: Zoledronic Acid / Zoledronate 4 MG/100 ML Intravenous Solution

NaCL 0.9%

PLACEBO COMPARATOR

NaCl 0.9%, perfusion IV Baseline Week 12 Week 24

Other: NaCL 0.9% Intravenous Solution

Interventions

Zoledronic Acid / Zoledronate 4 MG/100 ML Intravenous Solution DRUG

Baseline : 0.025 mg/kg ; Week 4 : 0.05 mg/kg ; Week 6 : 0.05 mg/kg

Zoledronate

NaCL 0.9% Intravenous Solution OTHER

Baseline, Week 4 \& Week 6

NaCL 0.9%

Eligibility Criteria

• Age: 4 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• aged ≥4 and \<17 years for whom:
• Written informed consent signed by the parents (the child may sign the consent if they wish, but their signature is not mandatory)

You may not qualify if:

• History of malignancy or current tumour
• History of seizure
• Current infectious osteomyelitis
• Contraindication to the study drug
• Hypersensitivity to the active substance, to other bisphosphonates, or to any excipient (sodium hydroxide, hydrochloric acid for pH adjustment, water for injection) ;
• Hypocalcemia ;
• Severe renal impairment with creatinine clearance \< 35 ml/min ;
• History of HIV, HBV, or HCV infection.
• Congenital or acquired prolonged QT interval (\>0.44 seconds) on ECG.
• Clinically significant vertebral deformities, including vertebral fracture and/or angular kyphosis with risk of spinal cord compression.
• Suspected or confirmed tuberculosis.
• History of renal or hepatic insufficiency.
• Already enrolled in another interventional study.
• Pregnant or breastfeeding participants
• Not affiliated with the French social security system.

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

Kremlin-Bicêtre Hospital

Le Kremlin-Bicêtre, Val De Marne, 94270, France

Location

MeSH Terms

Conditions

Osteomyelitis

Interventions

Zoledronic Acid

Condition Hierarchy (Ancestors)

Bone Diseases, Infectious; Infections; Bone Diseases; Musculoskeletal Diseases

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Perrine DUSSER, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Perrine DUSSER, MD, PhD

CONTACT

+33145213254; perrine.dusser@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: POMREP is a double-blinded multicentre prospective phase II proof-of-concept randomised controlled trial (parallel group 2:1) evaluating the efficacy of Zoledronate over a placebo in reducing pain for pediatric patients with CRMO.

Study Record Dates

• First Submitted: June 8, 2026
• First Posted: June 25, 2026
• Study Start (Estimated): September 15, 2026
• Primary Completion (Estimated): March 15, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: June 25, 2026

Record last verified: 2026-06

Locations

FR (1)