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Osteomyelitis ChronicPhase 2POMREPNCT07668583

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

A Phase 2 study testing Zoledronic Acid / Zoledronate 4 MG/100 ML Intravenous Solution and NaCL 0.9% Intravenous Solution in people with Osteomyelitis Chronic, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 4 to 17 years
Conditions the study is for
Osteomyelitis Chronic
What is being tested?
Zoledronic Acid / Zoledronate 4 MG/100 ML Intravenous Solution and NaCL 0.9% Intravenous Solution
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
30 participants
Where
1 siteFrance
Study dates
15 Sep 2026to 31 Dec 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 4 to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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 ;
Show all 18Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Perrine DUSSER, MD, PhD contact

+33145213254

perrine.dusser@aphp.fr

France1 site
  • Kremlin-Bicêtre Hospital

    Le Kremlin-Bicêtre, Val De Marne, 94270

    Perrine DUSSER, MD, PhD, +33145213254, perrine.dusser@aphp.fr

Other trials in France

About this study

Official title: 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.

Read the detailed description

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
Being tested
Zoledronic Acid / Zoledronate 4 MG/100 ML Intravenous Solution, NaCL 0.9% Intravenous Solution
Keywords
Osteomyelitis
Medical subject headings
Osteomyelitis

What participants receive

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

  • Zoledronic Acid / Zoledronate 4 MG/100 ML Intravenous SolutionDrug

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

  • NaCL 0.9% Intravenous SolutionOther

    Baseline, Week 4 \& Week 6

Study groups in NCT07668583
Study groupRoleWhat they receive
ZoledronateExperimentalZoledronic acid, perfusion IV Baseline : 0.025 mg/kg ; Week 12 : 0.05 mg/kg ; Week 24 : 0.05 mg/kg
Receives: Drug: Zoledronic Acid / Zoledronate 4 MG/100 ML Intravenous Solution
NaCL 0.9%Placebo comparatorNaCl 0.9%, perfusion IV Baseline Week 12 Week 24
Receives: Other: NaCL 0.9% Intravenous Solution

What is being measured

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

  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

    Measured: week 12

Secondary outcomes (14)
  1. Compare pain score (0-10 scale) evolution between groups at Weeks 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

    Measured: Week 4, 24 and 36

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

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

    Measured: Week 12, 24 and 36

  3. 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

    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.

    Measured: Week 12, 24 and 36

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

    compare biological inflammatory markers between the two groups at baseline and follow-up visits.

    Measured: Week 12, 24 and 36

  5. CNO Clinical Disease Activity Score (CNO CDAS)

    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.

    Measured: Week 12, 24 and 36

  6. Whole-body MRI disease activity assessed by the modified Radiological Index for Non-Bacterial Osteitis (mRINBO)

    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.

    Measured: Week 12, 24 and 36

  7. Proportion of participants achieving PedCNO30 response at 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%.

    Measured: week 36

  8. Radiological remission

    Compare the rate of radiological remission (early remission at week 12; remission at weeks 24 and 36) between the two groups.

    Measured: Week 12, 24 and 36

  9. Clinical and biological remission

    compare the rates of clinical and biological remission between the two groups at weeks 12, 24 and 36.

    Measured: Week 12, 24 and 36

  10. Health-related quality of life assessed by the Pediatric Quality of Life Inventory (PedsQL)

    PedsQL total score ranges from 0 to 100. Higher scores indicate better health-related quality of life.

    Measured: week 36

  11. 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

    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.

    Measured: week 36

  12. Safety and tolerability of zoledronate, assessed by the incidence of adverse events and serious adverse events during the 36-week follow-up period

    Measured: week 36

  13. Incremental cost-effectiveness ratio (ICER) of zoledronate versus placebo at 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.

    Measured: week 36

  14. Proportion of participants achieving PedCNO50 response at 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%.

    Measured: week 36

Timeline

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

  1. First posted25 Jun 2026
  2. Study start15 Sep 2026 (estimated)
  3. Primary completion15 Mar 2029 (estimated)
  4. Study completion31 Dec 2029 (estimated)

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07668583
Sponsor's protocol ID
APHP220795
Other IDs
2023-506420-93-00, 2023
Acronym
POMREP
Status last verified
Jun 2026
First submitted
8 Jun 2026
Last updated
25 Jun 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zoledronic Acid / Zoledronate 4 MG/100 ML Intravenous Solution and NaCL 0.9% Intravenous Solution in people with Osteomyelitis Chronic, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

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 4 inclusion and 18 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: opening soon, as of the sponsor's last update on 25 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Contact Perrine DUSSER, MD, PhD (+33145213254, perrine.dusser@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in pain score from baseline to week 12 (time frame: week 12). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 25 Jun 2026.

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