A Phase 2 Study of Burosumab for Fibroblast Growth Factor-23 Mediated Hypophosphatemia in Fibrous Dysplasia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Proportion of Participants With Serum Phosphate Levels Within the Target Range at Week 48
研究概览
简要总结
Background:
Fibrous dysplasia (FD) is a disorder that affects bone growth. Affected bone tissue is weakened, and people with FD are prone to deformities, fractures, and other problems. People with FD may also have low blood phosphate levels. This can make bones even weaker. Better treatments are needed.
Objective:
To test a study drug (burosumab) in people with FD who have low blood phosphate levels.
Eligibility:
People aged 1 year or older who have FD and low blood phosphate levels.
Design:
Participants will visit the NIH 3 times in 48 weeks. Each visit will last 5 to 7 days.
Participants will self-inject burosumab under the skin in their belly, upper arm, or thigh. They (or a caregiver) will do this at home 1 or 2 times a month. They will be trained in person on how to inject the drug. Home injections will be guided via telehealth.
During NIH visits, participants will have a physical exam with blood and urine tests. They will have x-rays of different parts of their body. They will have a radioactive tracer injected into their vein; then they will have a bone scan. They will have tests to assess their strength, walking, and movement. They will complete questionnaires about their pain, mobility, and fatigue levels.
Adult participants may have bone biopsies. These will be done under anesthesia with sedation. Small samples of FD-affected bone will be removed for study.
Between NIH visits, participants will go to a local laboratory for blood and urine tests.
Child participants will have an additional follow-up visit 2 weeks after the final NIH visit.
详细描述
Study Description:
This will be a phase 2, open-label, single-arm study to evaluate the safety and efficacy of burosumab to normalize serum phosphate levels in subjects with fibrous dysplasia (FD) and fibroblast growth factor 23 (FGF23)-mediated hypophosphatemia.
Objectives:
Primary Objective:
-Evaluate the efficacy of burosumab to normalize serum phosphate levels in subjects with FD and FGF23-mediated hypophosphatemia at 48 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 99 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- •Confirmed diagnosis of fibrous dysplasia
- •Serum phosphate <10th percentile for age and sex, AND intact serum FGF23 >=30 pg/mL
- •Age >=1 year
- •Provision of signed and dated informed consent/assent form
- •Stated willingness of subject or Legally Authorized Representative (LAR) to comply with all study procedures and availability for the duration of the study
- •For females of reproductive potential: agreement to use highly effective contraception for during study participation. Highly effective contraception methods include:
- •Total abstinence (when this is in line with the preferred and usual lifestyle of the participant). Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception
- •Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment.
- •Male sterilization (at least 6 months prior to screening). For female participants on the study the vasectomized male partner should be the sole partner for that participant.
- •Combination of the following (a+b or a+c, or b+c):
- •Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception
- •Placement of an intrauterine device (IUD) or intrauterine system (IUS)
- •Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
- •For males of reproductive potential: use of condoms or other methods described above to ensure effective contraception with partner
- •Minimum body weight of 7.5 kilograms
排除标准
- •An individual who meets any of the following criteria will be excluded from participation in this study:
- •Pregnancy or lactation
- •Known allergic reactions to burosumab or drug component
- •Treatment with another investigational drug within 30 days of screening
- •Treatment with burosumab within 30 days of screening
- •Have any condition which in the opinion of the PI could present a concern for subject safety or difficulty with data interpretation
- •Severe renal impairment or end stage renal disease, defined as: pediatric patients with estimated glomerular filtration rate (eGFR) 15 mL/min/1.73m2 to 29 mL/min/1.73m2 or end stage renal disease (eGFR < 15 mL/min/1.73m2), adult patients with creatinine clearance (CLcr) 15 mL/min to 29 mL/min or end stage renal disease (CLcr < 15 mL/min)
研究组 & 干预措施
Treatment with burosumab
Participants with Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) and hypophosphatemia receive burosumab subcutaneously dosed to the nearest 10mg. Pediatric participants receive 0.8mg/kg subcutaneously every two weeks for 48 weeks. Adult participants receive 0.5mg/kg subcutaneously every four weeks, with the option to receive dose every two weeks, for 48 weeks. All participants receive a minimum dose of 10mg/dose and a maximum of 90mg/dose.
干预措施: Burosumab (Drug)
结局指标
主要结局
Proportion of Participants With Serum Phosphate Levels Within the Target Range at Week 48
时间窗: Week 48
The proportion of participants who achieved serum phosphate levels within the target range (Z-score -1 to +2) at week 48. Analysis was done by dividing the number of number of participants who achieved serum level by the number of participants analyzed.
次要结局
- Participants With Adverse Event by Grade(48 weeks for adult participants; 50 weeks for pediatric participants)
- Participants With Related Adverse Event(48 weeks for adult participants; 50 weeks for pediatric participants)
- Proportion of Participants With Serum Phosphate Levels Within the Target Range at Week 24(Week 24)
- Proportion of Participants With Serum Phosphate Levels Above the Target Range (Z-score >+2)(Between baseline and week 48)
- Change in Serum Phosphate Level(Week 48 minus baseline)
- Percent Change in Serum Phosphate Level(Week 48 minus baseline)
- Change in Serum 1,25-dihydroxyvitamin D Level(Week 48 minus baseline)
- Percent Change in Serum 1,25-dihydroxyvitamin D Level(Week 48 minus baseline)
- Change in Serum Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR)(Week 48 minus baseline)
- Percent Change in Serum Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR)(Week 48 minus baseline)
- Change in Fibrous Dysplasia Lesion Activity Using Fluorine-18 Sodium Fluoride Positron Emission Tomography/Computed Tomography (18F-NaF PET/CT) Scan(Week 48 minus baseline)
- Change in Serum Procollagen 1 N-terminal Propeptide (P1NP) Level(Week 48 minus baseline)
- Percent Change in Serum Procollagen 1 N-terminal Propeptide (P1NP) Level(Week 48 minus baseline)
- Change in Serum Beta Crosslaps C-telopeptides (CTX) Level(Week 48 minus baseline)
- Percent Change in Serum Beta Crosslaps C-telopeptides (CTX) Level(Week 48 minus baseline)
- Change in Serum Osteocalcin Level(Week 48 minus baseline)
- Percent Change in Serum Osteocalcin Level(Week 48 minus baseline)
- Change in Serum Alkaline Phosphatase Level(Week 48 minus baseline)
- Percent Change in Serum Alkaline Phosphatase Level(Week 48 minus baseline)
- Change in Fibrous Dysplasia Lesion Cellularity(Week 48 minus baseline)
- Change in Patient Reported Outcome Measurement Information System (PROMIS) Score (Adult Version 2.0) - Pain Intensity Domain(Week 48 minus baseline)
- Change in Muscle Strength Using the Manual Muscle Test Scale(Week 48 minus baseline)
- Change in Muscle Range-of-motion(Week 48 minus baseline)
- Change in Walking Speed Measured by the 9-minute Walk Test (9MWT)(Week 48 minus baseline)
- Change in Patient Reported Outcome Measurement Information System (PROMIS) Score (Pediatric and Parent Proxy Version 2.0) - Pain Inference Domain(Week 48 minus baseline)
- Change in Quality of Life Measured by the 36-Item Short Form Health Survey (SF-36) Score(Week 48 minus baseline)
- Change in Health-related Quality of Life Measured by the 10-Item Short Form Health Survey (SF-10) - Physical Summary Score (PHS)(Week 48 minus baseline)
- Change in Patient Reported Outcome Measurement Information System (PROMIS) Score (Pediatric and Parent Proxy Version 1.0) - Pain Intensity Domain(Week 48 minus baseline)
- Change in Patient Reported Outcome Measurement Information System (PROMIS) Score (Adult Version 1.1) - Pain Inference Domain(Week 48 minus baseline)
- Change in Patient Reported Outcome Measurement Information System (PROMIS) Score (Pediatric and Parent Proxy Version 2.0) - Mobility Lower Extremity Domain(Week 48 minus baseline)
- Change in Patient Reported Outcome Measurement Information System (PROMIS) Score (Adult Version 2.0) - Mobility Lower Extremity Domain(Week 48 minus baseline)
- Change in Patient Reported Outcome Measurement Information System (PROMIS) Score (Pediatric and Parent Proxy Version 2.0) - Fatigue Domain(Week 48)
- Change in Patient Reported Outcome Measurement Information System (PROMIS) - Short Form - Fatigue 13a (Adult FACIT 13a v1.0)(Week 48)
- Proportion of Participants With Change in Activities of Daily Living (ADL) Questions(Week 48 minus baseline)