DEnosumab for the Treatment of FIbrous Dysplasia/McCune-Albright Syndrome in Adults (DeFiD): a Randomized Double-blind Placebo-controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 82
- 试验地点
- 1
- 主要终点
- Denosumab effect on maximal pain score
研究概览
简要总结
Fibrous Dysplasia/McCune-Albright syndrome (FD/MAS) is a rare disease, consisting of the replacement of normal bone tissue with fibrous tissue. FD lesions may be isolated in one or more bones or may be associated with endocrinopathies in McCune-Albright syndrome. Bone lesions constitute of weak bone tissue, leading to higher risk of fractures, pain and decreased quality of life. There is no cure for FD lesions and current therapies failed to soothe patients' complaints or to display any effect on progression of the lesions on imaging. However, the RANKL-inhibitor Denosumab demonstrated encouraging results in mouse models and in off-label clinical use, leading to clinical, biochemical and radiographical improvements.
Study's aim is to investigate whether 3-monthly Denosumab will improve the clinical, radiological and biochemical manifestations of FD bone lesions.
详细描述
Eligible patients will be randomized to treatment with either subcutaneous Dmab 120mg or placebo at baseline and 3 months in a blinded fashion. At 6 months, after 2 injections, patients with pain score <4 will exit the study to discontinue study medication and proceed in usual care, while patients with pain score ≥4 or lesional growth will be offered Dmab 120 mg at 6 and 9 months in an open-label design.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptomatic patients with established diagnosis of FD/MAS and closed growth plates(>18 years)
- •Pain in the region of an FD localization, not responding to adequate pain treatment and without mechanical component e.g. impending fracture
- •Pain score from FD lesion for maximum or average pain on VAS ≥ 4
- •Increased lesional activity defined as increased bone turnover markers (ALP, P1NP or CTX) or increased activity on Na[18F]-PET/CT or bone scintigraphy in at least one lesion
- •Normal levels of calcium, parathyroid hormone and vitamin D (supplementation is allowed)
- •Treated hypophosphatemia (defined as >0.7 at two separate measures)
- •good dental health (last check within the last 12 months)
排除标准
- •Active pregnancy wish, pregnancy or nursing
- •Pain not related to FD
- •Uncontrolled endocrine disease
- •Untreated vitamin D deficiency, hypocalcemia or hypophosphatemia
- •Previous use of bisphosphonates or Dmab < 6 months before inclusion ('6 months wash out')
- •Previously reported severe side effects on Dmab
- •Inability to fulfil study requirements
- •Poor untreated dental health without intention to get treatment
- •Treatment with other bone influencing drugs, such as high doses corticosteroids
研究组 & 干预措施
Denosumab
Denosumab randomized at baseline and 3 months in a double-blinded fashion and in case of open label at 6 and 9 months
干预措施: Denosumab 120 Mg/1.7 Ml Inj (Drug)
Placebo
Placebo randomized at baseline and 3 months in a double-blinded fashion.
干预措施: Placebo (Drug)
结局指标
主要结局
Denosumab effect on maximal pain score
时间窗: at baseline, 3 months and after 6 months and in case of open label treatment after 9 and 12 months
Evaluation of maximal pain score changes after treatment, assessed by Brief Pain Inventory (scale 0 to 10; 0-no pain, 10 worst pain)
次要结局
- Denosumab effect on average pain scores(at baseline, 3 months and after 6 months and in case of open label treatment after 9 and 12 months)
- To evaluate the number of patients with 50% reduction of maximal pain (BPI)(at baseline, 3 months and after 6 months and in case of open label treatment after 9 and 12 months)
- Denosumab effect on Physical activity assessment assessed through Health Assessment Questionnaire - Disability Index(baseline, 3 months and 6 months, and in case of open label treatment after 9 and 12 months)
- Evaluation of prevalence of possible neuropathic component of the reported pain(baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months)
- Denosumab effect on quality of life(at baseline, 3 months and after 6 months and in case of open label treatment after 9 and 12 months)
- Denosumab effect on average weekly pain score(every week from baseline, through study completion, an average of 1 year)
- Denosumab effect on Physical activity assessment assessed through screenshot of pedometer(baseline, 3 months and 6 months, and in case of open label treatment after 9 and 12 months)
- To investigate the number of analgesics used for pain(baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months)
- To investigate the frequency use of analgesics for pain(baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months)
- To investigate the dosage of analgesics used for pain(baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months)
- Denosumab effect on serum bone markers(baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months)
- Denosumab effect on serum markers(baseline, 3 months and 6 months and in case of open label treatment after 9 and 12 months)
- Denosumab effect on lesion size(baseline and after 6 months, and in the case of open label treatment after 12 months)
- Denosumab effect on lesion activity(baseline and after 6 months, and in the case of open label treatment after 12 months)
- disease quantification (Skeletal Burden Score (SBS)(at baseline, 6 months and after 12 months)
- Denosumab effect on bone density(baseline and after 12 months)
- Denosumab effect on vertebral fractures(baseline and after 12 months)
- To assess potential side effects in the form of Atypical femoral fractures(after 12 months)
研究者
Natasha Appelman-Dijkstra
Principal investigator, Internist-Endocrinologist, MD, PhD
Leiden University Medical Center