Phase 2a Study of Interferon Gamma-1b for the Treatment of Autosomal Dominant Type 2 Osteopetrosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Changes in Bone Resorption Markers From Baseline to 14 Weeks.
研究概览
简要总结
This study is an open label use of ACTIMMUNE for patients with Autosomal Dominant Osteopetrosis Type 2(ADO2). Effects of treatment will be evaluated after 14 weeks on ACTIMMUNE by bone resorption markers. This study will treat 12 patients with ADO2 recruited from Indiana University and Riley Hospital for Children at Indiana University Health.
详细描述
This is a single center, open-label, dose-escalation study evaluating the efficacy, as defined by biochemical endpoints, and safety profiles of ACTIMMUNE in ADO2 subject.
The investigators will treat 12 ADO2 subjects (children or adults age 3-65) with Actimmune® via a dose escalation protocol to a dose of 50 µg/m2 subcutaneously three times per week (TIW) for 8 weeks. If serum CTX does not increase by more than 25% by week 8, the dose will be increased to 100 µg/m2 subcutaneously TIW.
Individual subjects in whom ACTIMMUNE administration increases bone resorption markers during the 14 weeks of this trial will be eligible for a 1 year extension trial.
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
- 3 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject is diagnosed with clinically significant ADO2 as determined by the investigator.
- •Individuals will be screened who have either been diagnosed with osteopetrosis and have a clinical phenotype and/or family history that is consistent with ADO2, have been told that they have an abnormally high bone density (>3SD above mean for age and sex), or a clinical presentation consistent with ADO
- •Initial contact will be with members of ADO2 kindreds who have known disease.
- •Provide written informed consent for competent adults and for minors provide written assent (if appropriate) and written informed consent by a legally authorized representative after the nature of the study has been explained, and prior to any research-related procedures
- •Ages 3 to 65 years inclusive.
- •Willing to use reliable method of contraception [i.e. oral or patch hormonal contraceptives, intrauterine device, physical barrier methods, tubal ligation or hysterectomy, vasectomy (partner) or abstinence] throughout the study and for 30 days after the last dose of study drug.
排除标准
- •Any unstable illness that in the investigator's opinion precludes participation in the study.
- •Serum calcium >10.6 mg/dl at screening.
- •eGFR using the MDRD equation in adults (or the modified Schwartz equation for children) of < 35 ml/min/1.73m
- •Nephrocalcinosis on screening ultrasound Grade 3 or higher [18]. Subjects with grade 3 or higher nephrocalcinosis will be excluded because we anticipate that use of study drug will increase bone resorption, resulting in increased urinary calcium excretion, which could, potentially, lead to worsening nephrocalcinosis. The grading scale is listed below:
- •= Faint hyperechogenic rim around the sides and tip of the medullary pyramids
- •= More intense echogenic rim with echoes faintly filling the entire medullary pyramid
- •= Intense echoes throughout the medullary pyramid
- •= Solitary focus of echoes at the tip of the medullary pyramid/nephrolithiasis
- •Use of any investigational product (drug or device) within 30 days prior to randomization.
- •Subject reported history of hepatitis C.
- •A recent (past 5 years) history of alcoholism or intravenous drug abuse.
- •History of hypersensitivity to IFN-ɣ or E. coli-derived products.
- •History of liver disease as evidenced by laboratory results at Screening (aspartate aminotransferase [AST] or alanine aminotransferase [ALT] >2x the upper limit of normal), except when in the opinion of the investigator the liver disease is caused by extra medullary hematopoiesis.
- •Pregnant or nursing women or those who plan on becoming pregnant during the study.
研究组 & 干预措施
Treatment
ACTIMMUNE 50 µg/m2 subcutaneously three times per week (TIW) for 8 weeks
干预措施: ACTIMMUNE (Drug)
结局指标
主要结局
Changes in Bone Resorption Markers From Baseline to 14 Weeks.
时间窗: baseline, 14 weeks
Evaluate for changes in bone resorption markers including CTX, NTX/creatinine ratio between baseline and 14 weeks
次要结局
- Change in Bone Turnover Markers Between After Completion of 6-12 Weeks of Treatment(6-12 weeks)
研究者
Michael Econs
MD, Professor of Endocrinlogy and Metabolism
Indiana University