ClinicalTrials.gov record NCT07668583
EFFICACY AND SAFETY OF ZOLEDRONATE VERSUS PLACEBO ON PAIN AT WEEK 12 IN PEDIATRIC PATIENTS WITH CHRONIC RECURRENT MULTIFOCAL OSTEOMYELITIS
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
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Phase 2 randomized, quadruple-masked trial comparing zoledronate with placebo in children aged ≥4 and <17 years who have NSAID-resistant chronic recurrent multifocal osteomyelitis (CRMO). The main outcome is change in standardized pain score from baseline to week 12. Participants receive intravenous infusions of zoledronate or matching saline placebo at scheduled visits and are followed through week 36.
What it is studying. The study tests the effect of zoledronate versus placebo on pain at week 12, and also assesses safety, imaging (MRI) changes, inflammatory markers, disease activity scores, quality of life, remission rates, and cost-effectiveness in children with NSAID-resistant CRMO.
What the researchers hope to learn. Scientific goals: measure change in pain from baseline to week 12; compare pain over time (weeks 4, 24, 36); compare MRI disease activity, biological inflammatory markers, clinical disease activity scores (CNO CDAS), PedCNO response rates, radiological and clinical remission rates, health-related quality of life, school/work absenteeism, safety and tolerability, and cost-effectiveness of zoledronate versus placebo.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Zoledronic Acid / Zoledronate 4 MG/100 ML Intravenous Solution
- Other
- NaCL 0.9% Intravenous Solution
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
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.
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
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:
- To compare pain evolution between the two groups at weeks 4, 24 and 36 (pain at week 12 being the primary endpoint).
- To compare the use of NSAIDs, other analgesics and corticosteroids between the two groups during follow-up.
- 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.
- To compare biological inflammatory markers between the two groups at baseline and follow-up visits.
- To evaluate disease activity using the CNO Clinical Disease Activity Score (CNO CDAS) between the two groups at baseline and follow-up visits.
- To compare radiological disease activity on whole-body MRI between the two groups at baseline and follow-up visits using the mRINBO score.
- To assess treatment response using PedCNO30 and PedCNO50 score between the two groups at baseline and follow-up visits.
- To compare the rate of radiological remission (early remission at week 12; remission at weeks 24 and 36) between the two groups.
- To compare the rates of clinical and biological remission between the two groups at weeks 12, 24 and 36.
- To evaluate changes in health-related quality of life between the two groups at baseline and follow-up visits.
- To assess the impact on schooling (children) and work absenteeism (parents) between the two groups.
- To evaluate the safety and tolerance of zoledronate.
- To assess the cost-effectiveness of the strategy
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants are randomized to receive intravenous zoledronate or matching placebo at three timepoints (baseline, week 12, week 24). They will attend clinic visits for pain scoring at baseline and at weeks 4, 12, 24 and 36 (with clinical exams at baseline and weeks 12, 24 and 36), provide blood samples for safety and inflammatory markers, and complete quality-of-life questionnaires; whole-body MRI is performed at baseline and at weeks 12, 24 and 36. Participants (or parents) will use an electronic diary (ePRO) to record school/work absenteeism and medication use; study staff will monitor for adverse events throughout follow-up. A dental review and vitamin D testing are required before the first infusion, and any needed invasive dental work must be completed beforehand.
How the study is structured. Phase 2, randomized, parallel‑group, quadruple‑masked (participant, care provider, investigator, outcomes assessor) trial. Children are randomly assigned to receive either zoledronate or a saline placebo by intravenous infusion at several scheduled visits; outcomes are measured through week 36. (Note: the registry lists infusion timing but contains inconsistent entries regarding exact visit weeks.)
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The registry says recruitment has not started. When is it expected to open, and can I register interest now?
- The listed sites are in France. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on chronic recurrent multifocal osteomyelitis
Important dates
- Study start
- Sep 15, 2026 (estimated)
- Primary completion
- Mar 15, 2029 (estimated)
- Study completion
- Dec 31, 2029 (estimated)
- Target enrollment
- 30 participants (estimated)
- Last updated on registry
- Jun 25, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Perrine DUSSER, MD, PhD 📞 +33145213254 ✉ perrine.dusser@aphp.fr
Participating sites (1)
- Kremlin-Bicêtre Hospital
Le Kremlin-Bicêtre, Val De Marne, 94270 · France
- Perrine DUSSER, MD, PhD · +33145213254 · perrine.dusser@aphp.fr
Terms used on this page · explanations by MedicalUpdates.ai
- line of therapy
- Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
- placebo
- A treatment that looks like the study treatment but contains no active ingredient. Some participants receive it instead of the study treatment, usually without knowing which they got.
- baseline
- Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
- MRI
- A scan that uses magnets and radio waves, not X-rays, to make detailed pictures of the inside of the body. Some implants and metal objects mean a person cannot have one.
- primary endpoint
- The main result the study is designed to measure and report on. Other results, called secondary outcomes, are also collected.
- endpoints
- Something the study measures to judge its results, such as a symptom score, a blood test or survival. Outcomes are grouped as primary, secondary and sometimes exploratory.
- stable dose
- A dose that has not changed for a defined period before the study starts. Studies may require this so that background treatment is relatively stable when study measurements begin.
- Written informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- Contraindication
- A reason a particular test or treatment should not be used for a person, for example a metal implant that rules out an MRI scan.
- study drug
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- creatinine clearance
- A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
- ECG
- A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged.
- at screening
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- corticosteroids
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- follow-up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
← Back to clinical trials