EUCTR2018-001309-95-PL进行中（未招募）1 期
A Phase 2, proof-of-concept, multicentre, double-blind, randomised, dose-ascending, sequential group, placebo-controlled study to evaluate the mechanistic effect, safety, and tolerability of 12 weeks twice daily oral administration of alvelestat (MPH966) in participants with alpha-1 (PiZZ or null genotype/phenotype) antitrypsin deficiency.
Mereo BioPharma 4 Ltd0 个研究点目标入组 182 人开始时间: 2018年12月10日最近更新:
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 182
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •1. Age 18 to 75 years at screening
- •2.Participants with a diagnosis or confirmation of AATD (PiZZ or, null or
- •other rare phenotype/genotype) with an associated serum AAT
- •levelslevel of <11 µM or <57.2 mg/dL
- •3.Post-bronchodilator FEV1=20% predicted at screening
- •4.Computerised tomography (CT) scan evidence of emphysema
- •5.Non-smokers (for at least 12 months prior to baseline)
- •6.Absence of advanced liver fibrosis or cirrhosis:
- •a.Fibrosis-4 (FIB-4) score <1.45 or
- •b.FIB-4 score >1.45 and =3.25 with transient elastography
- •measurement <12.5 kPa within 3 months of baseline
- •7.Male or female
- •Male participants: A male participant must agree to use a highly effective
- •contraception as detailed in Appendix 5 during the treatment period and
- •for at least 4 days after the last dose of study treatment and refrain from
- •donating sperm during this period
- •Female participants: A female participant is eligible to participate if she
- •is not pregnant (see Appendix 5), not breastfeeding, and at least 1 of the
- •following conditions applies:
- •a.Not a woman of childbearing potential as defined in Appendix 5 OR
- •b.A woman of childbearing potential who agrees to follow the
- •contraceptive guidance in Appendix 5 during the treatment period and
- •for at least 4 days after the last dose of study treatment
- •8.Capable of giving signed informed consent as described in Appendix 3,
- •which includes a commitment to comply with the requirements and
- •restrictions listed in the informed consent form (ICF) and within this
- •Are the trial subjects under 18? no
- •Number of subjects for this age range:
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range 127
- •F.1.3 Elderly (>=65 years) yes
- •F.1.3.1 Number of subjects for this age range 55
排除标准
- •1. Participants with PiMZ, PiFF or PiSZ AATD phenotypes/genotypes
- •2. Primary clinical diagnosis of bronchiectasis or evidence of significant
- •bronchiectasis on CT scan (per Investigator judgement and with CT scan
- •performed during the 3 years prior to dosing)
- •3. Acute exacerbation of underlying lung disease requiring oral
- •corticosteroids, antibiotics, and/or change in regular treatments within
- •4 weeks of baseline
- •4. Acute or chronic hepatitis, including hepatitis B and or C virus
- •infection (positive hepatitis B surface antigen, and /or hepatitis C
- •antibody) at screening
- •5. Known history or present diagnosis of cirrhosis (on imaging or
- •biopsy), oesophageal varices, ascites or hepatic encephalopathy
- •6. History of other chronic liver diseases such as autoimmune hepatitis,
- •primary biliary cholangitis, primary sclerosing cholangitis, Wilson's
- •disease, haemochromatosis
- •7. History of non-alcoholic fatty liver disease (NAFLD).
- •8. History of significant alcohol consumption for a period of more than 3
- •consecutive months within 1 year prior to screening, defined as an average of >20 g / day in female subjects and >30 g/ day in male
- •(For reference, 14g of alcohol are contained in the following: 12fl oz
- •(355ml) regular beer containing ~5% alcohol; 8-9fl oz (235 to 265ml)
- •malt liquor containing ~7% alcohol; 5fl oz (150ml) of table wine
- •containing ~12% alcohol or 1.5fl oz (45ml) of distilled spirits (e.g. gin,
- •rum, vodka, whiskey) containing ~40% alcohol)
- •9. History of alcohol and/or drug abuse within the 15 years prior to
- •10. HIV infection OR known other immunodeficiency OR an absolute
- •neutrophil count =1.0 × 109/L at screening
- •11. Any of the following lab abnormalities suggestive of liver disease:
- •abnormal liver-related biochemistry at screening (alanine
- •aminotransferase, aspartate aminotransferase) >1.5 × upper limit of
- •normal OR gamma-glutamyl transferase >2 × upper limit of normal OR
- •total bilirubin > upper limit of normal (unless Gilbert's disease with
- •normal conjugated bilirubin), platelet count <150 x 109/L, serum
- •albumin = 3.5g/dL or INR =1.2 (in the absence of drugs known to
- •elevate INR, for example anticoagulant therapy) or CPK =1.5 x ULN
- •12. FIB-4 score >3.25 at screening
- •13. Any of the following cardiovascular conditions within 6 months
- •prior to the screening visit:
- •a. Myocardial infarction or unstable angina
- •b. Stroke or transient ischaemic attack
- •c. Coronary artery bypass surgery, balloon angioplasty, percutaneous
- •coronary intervention, or carotid revascularisation procedure
- •d. Uncontrolled hypertension within the 3 months prior to screening in
- •the Investigators judgement
- •e. Congestive heart failure (New York Heart Association III/IV)
- •14. Any clinically significant 12-lead electrocardiogram abnormalities at
- •screening or baseline OR corrected QT interval by Fridericia's correction
- •method >450 ms OR history of significant cardia dysrhythmia, including
- •long QT syndrome
- •15. Significant renal disease or infection (as determined by the
- •Investigator) including stage 4 chronic kidney disease or estimated
- 另有 8 项未显示
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