NCT02679014已完成1 期
A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Parallel Study to Investigate the Pharmacokinetics, Pharmacodynamic Effects, Safety and Tolerability of Repeated Dosing of RO5459072 in Volunteers With Celiac Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Overall Numbers of Participants who are Responders to the Gluten Challenge, Defined as Participants with an Increase in Number of Gliadin Specific T-cells Above Assay-Specific Thresholds
研究概览
简要总结
A randomized, double-blind, placebo-controlled, two treatment, parallel group study to investigate the effects of RO5459072, a cathepsin S inhibitor, on the immune response to a gluten challenge in volunteers with celiac disease. Volunteers with previously diagnosed celiac disease will be randomized to receive either 100 milligrams (mg) RO5459072 or placebo twice daily with food for 28 days (Days 1 to 28).
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Volunteers with a biopsy confirmed diagnosis of celiac disease
- •Human leukocyte antigen (HLA) serotype DQ 2.5 and HLA-DQ 8 haplotypes
- •Maintaining a gluten-free diet for at least one year. Compliance will be assessed by serology, compatible responses to a self-reported assessment of gluten-free diet adherence and the absence of typical celiac disease symptoms
- •Able to participate and to comply with the study restrictions including the requirements of the gluten challenge
排除标准
- •A diagnosis of non-celiac gluten sensitivity
- •A personal history of food intolerance other than to gluten, or diagnosis of galactosemia, lactose, galactose or fructose intolerance
- •A personal history of severe acute symptomatic reaction to sporadic gluten ingestion
- •A diagnosis of refractory celiac disease or presence of severe complications of celiac disease
- •Diagnosed or suspected immunoglobulin A (IgA) deficiency
- •Acute inflammatory bowel disease (ulcerative colitis, Crohn's disease), gastrointestinal obstruction or sub-occlusive syndromes, digestive perforation or risk of digestive perforation, painful abdominal syndromes of undetermined cause
- •A history of stomach or intestinal surgery or resection. Appendectomy and hernia repair are acceptable
- •Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple allergies (non-active hay fever is acceptable)
- •Immunocompromised or with reduced immune function considered to be clinically significant by the Investigator
- •Immunization within 30 days before the screening visit or planning vaccination during the study
- •Women who are pregnant or lactating, or who are of child-bearing potential and do not agree to comply with requirements for contraceptive use. Men who do not agree to comply with requirements for contraceptive use and restrictions on sperm donation
- •Participation in an investigational drug or device study within the three months preceding the screening visit
研究组 & 干预措施
Placebo
Placebo Comparator
Participants will receive placebo capsules (2 capsules) twice daily for 28 days.
干预措施: Placebo (Drug)
RO5459072
Experimental
Participants will receive RO5459072 100 milligrams (mg) capsules (2*50 mg capsules) twice daily for 28 days.
干预措施: RO5459072 (Drug)
结局指标
主要结局
Overall Numbers of Participants who are Responders to the Gluten Challenge, Defined as Participants with an Increase in Number of Gliadin Specific T-cells Above Assay-Specific Thresholds
时间窗: Day 13 and Day 29
次要结局
- Percentage of Participants with Adverse Events (AEs)(Up to Day 35)
- Number of Participants with an Increase in Antibody Titers (Anti-Tissue Transglutaminase [anti-tTG] Immunoglobulin A [IgA] and Immunoglobulin G [IgG] and Anti-Deamidated Gliadin Peptide (anti-DPG) IgA), as Determined Using Enzyme Immunoassay Methods(Screening, Day 7, Day 13, Day 21, Day 29 and Day 35 (Follow up))
- Lactulose to Mannitol Ratio (LMR), Determined by Urine Concentrations of Lactulose and Mannitol(Day 7: 1 hour (hr) pre-dose to 1 hr post-dose, 1 hr to 3 hr post-dose, 3 hr to 5 hr post-dose and Day 21: 1 hr pre-dose to 1 hr post-dose, 1 to 3 hr post-dose, 3 hr to 5 hr post-dose)
- Change from Baseline in Number of Circulating White Blood Cells(Day 1 (Baseline), Day 7, Day 13, Day 21, and Day 29)
- Change from Baseline in Concentrations of the 10 kilodalton (kDa) Cluster of Differentiation 74 (CD74) Intermediate (Fragment p10) in B Cells(Day 1: pre-dose (=Baseline [BL]) and 4 hours (h) post-dose, Day 7: pre-dose and 4 h post-dose, Day 21: pre-dose and 4 h post-dose)
- Change from Baseline in Concentrations of Cathepsin S Mass Biomarker(Day 1 (Baseline), Day 7, Day 13, Day 21 and Day 29)
- Change from Baseline in Concentrations of Cystatin C Biomarker(Day 1 (Baseline), Day 7, Day 13, Day 21 and Day 29)
- Maximum Response (Emax ) in p10 upon Cathepsin S Inhibition Ex vivo(Day 1: pre-dose)
- Concentration of RO5459072 that Gives Half-maximal Response (EC50) in Ex Vivo p10 Stimulation Assay(Day 1: pre-dose)
- Change from Baseline in 4Beta-hydrocholesterol Concentration(Day 1 (Baseline), Day 7, Day 13, Day 21 and Day 29)
研究者
研究点 (1)
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