2023-506420-93-00招募中2 期
POMREP - 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
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 12
- 主要终点
- Change in standardized pain score (0–10 scale) from baseline to week 12, assessed using an age-appropriate validated self-assessment scale on a 0–10 metric: the Faces Pain Scale–Revised (FPS-R, 0–10) for children aged ≥4 and <6 years, the pediatric visual analog scale (VAS, 0–10) for children aged ≥6 years who are able to do so, and the Numerical Rating Scale (NRS, 0–10) for children aged ≥8 years, depending on comprehension and feasibility.
研究概览
简要总结
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.
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 接受健康志愿者
- 否
入选标准
- •Children or teenagers (≥ 4 years and <17 years)
- •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.
排除标准
- •History of malignancy or current tumour
- •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) ;
- •Contraindication to the study drug : Hypocalcemia
- •Contraindication to the study drug : 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.
- •ECG: check for congenital or acquired long QT > 0.44sec
- •Pregnant or breastfeeding participants
- •Serum 25-hydroxy vitamin D level <30 ng/mL at screening/baseline. These patients will not be randomized until correction of vitamin D deficiency and may be re-screened once vitamin D level is ≥30 ng/mL
- •Clinically significant vertebral deformities, including vertebral fracture and/or angular kyphosis with risk of spinal cord compression
- •Suspected tuberculosis.
- •History of renal or hepatic insufficiency.
- •Already enrolled in another interventional study.
- •Not affiliated with the French social security system.
- •Patient or legal guardians with limited understanding of the French language
- •History of seizure
- •Current infectious osteomyelitis
研究组 & 干预措施
PLACEBO OF ZOLEDRONIC ACID
Placebo
干预措施: PLACEBO OF ZOLEDRONIC ACID (Drug)
ZOLEDRONIC ACID
Test
干预措施: ZOLEDRONIC ACID (Drug)
结局指标
主要结局
Change in standardized pain score (0–10 scale) from baseline to week 12, assessed using an age-appropriate validated self-assessment scale on a 0–10 metric: the Faces Pain Scale–Revised (FPS-R, 0–10) for children aged ≥4 and <6 years, the pediatric visual analog scale (VAS, 0–10) for children aged ≥6 years who are able to do so, and the Numerical Rating Scale (NRS, 0–10) for children aged ≥8 years, depending on comprehension and feasibility.
Change in standardized pain score (0–10 scale) from baseline to week 12, assessed using an age-appropriate validated self-assessment scale on a 0–10 metric: the Faces Pain Scale–Revised (FPS-R, 0–10) for children aged ≥4 and <6 years, the pediatric visual analog scale (VAS, 0–10) for children aged ≥6 years who are able to do so, and the Numerical Rating Scale (NRS, 0–10) for children aged ≥8 years, depending on comprehension and feasibility.
次要结局
- Tolerance of ZA is defined by the occurrence of flu-like symptoms, headache, hypophosphatemia, hypocalcaemia.
- Efficiency is defined as the incremental cost-effectiveness ratio in cost per quality-adjusted life-year gained.
- Assessment at baseline, week 12, 24 and 36 of inflammatory syndrome by clinicians using blood analyses to determine the frequency of children over the norm for: Rate of White Blood Cells (WBC> 10 000/mm3) / Rate of platelets (> 400 000/mm3) / Rate of C Reactive Protein (>5mg/l) / Sedimentation Rate (> 10mm) / And rate of pro-inflammatory cytokines
- Quality of life of children will be assessed at baseline and week 12, 24 and 36 using the PedSQL (Pediatric Quality of Life Inventory) questionnaire. It is a validated instrument with an international application designed to measure children’s health-related quality of life in four dimensions. The questionnaire will be completed by the child (self-report) if ≥ 8 years of age and by the parents (proxy-report) for younger children, with both reports collected when possible.
- School and parental absenteeism will be defined by the number of days of absence from school or work for every period of 12 weeks. It will be measured at baseline, week 12, 24 and 36
- Pain assessment will be performed at baseline and weeks 4, 24 and 36 by the patient, using the same age-appropriate validated scales as for the primary endpoint. A reduction of pain ≥30% from baseline will be considered as clinically meaningful improvement, and a reduction of ≥50% as substantial improvement, assessed at weeks 4, 12, 24 and 36. Clinical remission is defined as complete disappearance of pain with a pain score of 0, assessed at weeks 12, 24 and 36
- NSAIDs consumption will be measured by the average number of days with NSAIDs intake in the last 3 months. Other pain killers’ intakes or corticosteroids will also be recorded. Patients will receive a diary to collect information about pain medications. The consumption of NSAIDs and other pain killers will be assessed at weeks 12, 24 and 36.
- Clinical signs will be compared between the two study groups at baseline, week 12, 24 and 36. The main clinical signs assessed during the physical exams of the patient will be: Pain on joint palpation / Arthritis / Spinal deformation / Extra-osseous manifestations: dermatologic manifestations (acne, palmoplantar pustulosis and psoriasis), synovitis, and inflammatory bowel disease / Staturo-ponderal growth and puberty
- Disease activity will be assessed using the CNO Clinical Disease Activity Score (CNO CDAS), a composite score developed specifically for chronic nonbacterial osteomyelitis. The CNO CDAS includes the following three components: Patient (or parent) pain assessment on a 0–10 visual analog scale (VAS) / Patient (or parent) global assessment of disease activity on a 0–10 VAS / Clinician-reported count of clinically active CNO lesions (0 to 10)
- Radiological assessment on whole-body MRI evaluated at baseline, week 12, 24 and 36: number of unequivocal lesions, number of new lesions since the previous MRI, and mRINBO score (including change from baseline)
- Treatment response will be assessed using the PedCNO composite score at baseline, week 12, 24 and 36. Both PedCNO30 and PedCNO50 will be considered as secondary endpoints. PedCNO30 and PedCNO50 are defined as at least 30% and 50% improvement, respectively, in at least three out of five core set variables, with no more than one of the remaining variables deteriorating by more than 30% or 50%, respectively. / ESR / Number of radiological lesions / VAS physician / VAS patient/parents / CHAQ
- Radiological remission, defined as MRI negativity (normalisation of MRI). Early remission will be assessed at week 12 and remission at week 24 and 36.
- Clinical and biological remission, defined as the complete disappearance of pain and inflammatory syndrome. Clinical and biological remission will be assessed at week 12, 24 and 36.
研究者
Perrine DUSSER
Scientific
Assistance Publique Hopitaux De Paris
研究点 (12)
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