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

21 giugno 2026 aggiornato da: Assistance Publique - Hôpitaux de Paris

EFFICACY AND SAFETY OF ZOLEDRONATE VERSUS PLACEBO ON PAIN AT WEEK 12 IN PEDIATRIC PATIENTS WITH CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS RESISTANT TO NON-STEROIDAL ANTI-INFLAMMATORY DRUG

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.

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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 to 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.

Main objective: To evaluate the efficacy of zoledronate, administered at increasing doses (0.025 mg/kg at baseline, 0.05 mg/kg at week 12, and 0.05 mg/kg at week 24; maximum dose 4 mg per infusion), versus placebo on the change in standardized pain score (0-10 scale) from baseline to week 12 in children aged ≥4 and <17 years with NSAID-resistant CRMO.

Secondary objectives:

  1. To compare pain evolution between the two groups at weeks 4, 24 and 36 (pain at week 12 being the primary endpoint).
  2. To compare the use of NSAIDs, other analgesics and corticosteroids between the two groups during follow-up.
  3. To compare clinical signs (pain on palpation, arthritis, spinal deformity, extra-osseous manifestations, growth and puberty) between the two groups at baseline and follow-up visits.
  4. To compare biological inflammatory markers between the two groups at baseline and follow-up visits.
  5. To evaluate disease activity using the CNO Clinical Disease Activity Score (CNO CDAS) between the two groups at baseline and follow-up visits.
  6. To compare radiological disease activity on whole-body MRI between the two groups at baseline and follow-up visits using the mRINBO score.
  7. To assess treatment response using PedCNO30 and PedCNO50 score between the two groups at baseline and follow-up visits.
  8. To compare the rate of radiological remission (early remission at week 12; remission at weeks 24 and 36) between the two groups.
  9. To compare the rates of clinical and biological remission between the two groups at weeks 12, 24 and 36.
  10. To evaluate changes in health-related quality of life between the two groups at baseline and follow-up visits.
  11. To assess the impact on schooling (children) and work absenteeism (parents) between the two groups.
  12. To evaluate the safety and tolerance of zoledronate.
  13. To assess the cost-effectiveness of the strategy

Tipo di studio

Interventistico

Iscrizione (Stimato)

30

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Luoghi di studio

  • Francia
    • Val De Marne
      • Le Kremlin-Bicêtre, Val De Marne, Francia, 94270
        • Kremlin-Bicêtre Hospital
        • Contatto:

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Bambino

Accetta volontari sani

No

Descrizione

Inclusion Criteria:

  • aged ≥4 and <17 years for whom:
  • Physician-confirmed diagnosis of CRMO according to Jansson's criteria, with compatible MRI findings. Having lesions on MRI within 12 weeks prior to inclusion and clinically active disease defined by at least one of 2 criteria: patient/parent VAS (pain) superior or equal to 30/100 and/or physician VAS superior or equal to 30/100 after failure of at least 4 weeks of NSAIDs at a stable dose
  • Written informed consent signed by the parents (the child may sign the consent if they wish, but their signature is not mandatory)
  • Having had a dental review within 3 months prior to inclusion, with completion of any necessary invasive dental work before the first dose of zoledronate.

Exclusion Criteria:

  • 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 ;
  • Prior treatment with bisphosphonates and/or biotherapy within 6 months prior to inclusion.
  • 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.
  • Patient or legal guardians with limited understanding of the French language
  • Serum 25-hydroxy vitamin D level <30 ng/mL at screening. Participants may be re-screened after correction of vitamin D deficiency.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Quadruplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: Zoledronate
Zoledronic acid, perfusion IV Baseline : 0.025 mg/kg ; Week 12 : 0.05 mg/kg ; Week 24 : 0.05 mg/kg
Droga: Zoledronic Acid / Zoledronate 4 MG/100 ML Intravenous Solution
Baseline : 0.025 mg/kg ; Week 4 : 0.05 mg/kg ; Week 6 : 0.05 mg/kg
Comparatore placebo: NaCL 0.9%
NaCl 0.9%, perfusion IV Baseline Week 12 Week 24
Altro: NaCL 0.9% Intravenous Solution
Baseline, Week 4 & Week 6

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Change in pain score from baseline to week 12
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Compare pain score (0-10 scale) evolution between groups at Weeks 4, 24 and 36
Lasso di tempo: Week 4, 24 and 36
Change in standardized pain score (0-10 scale) from baseline to week 4,24 &36, using Visual Analog Scale VAS 0-10/ 0 = no pain ; 10 = worst imaginable pain
Week 4, 24 and 36
Use of NSAIDs, other analgesics and corticosteroids between the two groups during follow-up.
Lasso di tempo: Week 12, 24 and 36
compare the 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
Lasso di tempo: Week 12, 24 and 36
Clinical manifestations will be assessed by physical examination at baseline and at weeks 12, 24 and 36. The proportion of participants presenting each manifestation (pain on palpation, arthritis, spinal deformity, dermatological manifestations, inflammatory bowel disease, growth impairment and pubertal delay) will be compared between groups.
Week 12, 24 and 36
Biological inflammatory markers between the two groups at baseline and follow-up visits.
Lasso di tempo: Week 12, 24 and 36
compare 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)
Lasso di tempo: Week 12, 24 and 36
The Chronic Nonbacterial Osteomyelitis Clinical Disease Activity Score (CNO CDAS) is a composite disease activity score consisting of three components: (1) patient/parent pain assessment (0-10 visual analog scale), (2) patient/parent global assessment of disease activity (0-10 visual analog scale), and (3) physician assessment of the number of clinically active CNO lesions (0-10). Total scores range from 0 to 30, with higher scores indicating greater disease activity and a worse clinical condition. The CNO CDAS will be assessed at baseline and at weeks 12, 24, and 36.
Week 12, 24 and 36
Whole-body MRI disease activity assessed by the modified Radiological Index for Non-Bacterial Osteitis (mRINBO)
Lasso di tempo: Week 12, 24 and 36
The mRINBO score will be assessed on whole-body MRI at baseline and follow-up visits. The score incorporates the number of radiologically active lesions, the maximum lesion size (RALmax), extramedullary inflammatory changes, and chronic radiological changes. Higher scores indicate greater radiological disease activity. Whole-body MRI assessments will be performed at baseline and at weeks 12, 24, and 36.
Week 12, 24 and 36
Proportion of participants achieving PedCNO30 response at week 36
Lasso di tempo: week 36
PedCNO30 is defined as at least 30% improvement in at least three of five core variables, with no more than one variable worsening by >30%.
week 36
Radiological remission
Lasso di tempo: Week 12, 24 and 36
Compare the rate of radiological remission (early remission at week 12; remission at weeks 24 and 36) between the two groups.
Week 12, 24 and 36
Clinical and biological remission
Lasso di tempo: Week 12, 24 and 36
compare the rates of clinical and biological remission between the two groups at weeks 12, 24 and 36.
Week 12, 24 and 36
Health-related quality of life assessed by the Pediatric Quality of Life Inventory (PedsQL)
Lasso di tempo: week 36
PedsQL total score ranges from 0 to 100. Higher scores indicate better health-related quality of life.
week 36
Number of days of school absenteeism (children) and work absenteeism (parents) recorded using the electronic patient-reported outcome (ePRO) diary, during each 12-week period
Lasso di tempo: week 36
School and parental absenteeism will be assessed as the number of days missed from school by the child and the number of days missed from work by the parent during the previous 12 weeks. Data will be collected using the electronic patient-reported outcome (ePRO) diary and compared between treatment groups.
week 36
Safety and tolerability of zoledronate, assessed by the incidence of adverse events and serious adverse events during the 36-week follow-up period
Lasso di tempo: week 36
week 36
Incremental cost-effectiveness ratio (ICER) of zoledronate versus placebo at week 36
Lasso di tempo: week 36
Cost-effectiveness will be assessed by estimating the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY) gained.
week 36
Proportion of participants achieving PedCNO50 response at week 36
Lasso di tempo: week 36
PedCNO50 is defined as at least 50% improvement in at least three of five core variables, with no more than one variable worsening by >50%.
week 36

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigatori

  • Investigatore principale: Perrine DUSSER, MD, PhD, Assistance Publique - Hôpitaux de Paris

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

15 settembre 2026

Completamento primario (Stimato)

15 marzo 2029

Completamento dello studio (Stimato)

31 dicembre 2029

Date di iscrizione allo studio

Primo inviato

8 giugno 2026

Primo inviato che soddisfa i criteri di controllo qualità

21 giugno 2026

Primo Inserito (Effettivo)

25 giugno 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

25 giugno 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

21 giugno 2026

Ultimo verificato

1 giugno 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • APHP220795
  • 2023-506420-93-00 (Ctis)

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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