EUCTR2015-000484-13-GB进行中（未招募）1 期
A Phase 2, Open Label, Randomized, Dose Ranging, Safety, Efficacy, Pharmacokinetic and Pharmacodynamic Study of AG-348 in Adult Patients with Pyruvate Kinase Deficiency
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 75
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
- •Core period:
- •1.Signed written informed consent obtained prior to performing any study procedure, including screening procedures
- •2.M/F, aged .18 yrs
- •3.Known medical history of PKD
- •4.Patients must have documented clinical laboratory confirmation of PKD by RBC PK enzymatic assay performed at Screening or by any participating investigative site's local hematology laboratory. Patients with prior documentation of PKD by RBC enzymatic assay will have a reconfirmation of this result during Screening as a condition of enrollment
- •a.In the event that a patient's screening PK enzymatic assay is negative, the patient will be eligible for enrollment if the genotyping shows a mutant genotype that has been previously documented in the literature to be associated with PKD. If the genotyping shows a previously undescribed mutation in the PKR gene, then the eligibility for enrollment will be determined on a case-by-case basis. If no mutation is defined, then the patient will not be eligible
- •5.Patients must have genotypic characterization of the mutant PKR gene performed at Screening.Patients whose genotype has already been determined by another laboratory may be enrolled on the basis of that report, with the approval of the Medical Monitor.
- •6.Patients must have genotypic characterization of the UGT1A1 gene performed to document whether they may have underlying Gilbert's Disease. Patients with Gilbert's Disease are eligible to enroll
- •7.Males must have Hb . 12.0 g/dL; females must have Hb . 11.0 g/dL
- •8.Patients must be considered transfusion independent as defined by: no greater than 3 units of RBCs transfused in the 12-month period up to the first day of study dosing and no transfusions within 4 months of first day of study dosing. Patients who have received more transfusion support than described above will evaluated for eligibility on a case-by-case basis
- •9. Eligible patients may still have their spleens in place, or may have undergone prior splenectomy
- •Splenectomized patients:
- •a.Must have undergone their procedure at least 6 months prior to Screening
- •b.Must be current in their vaccinations for Pneumococcal Conjugate (PCV13), Pneumococcal Polysaccharide (PPSV23), Quadrivalent Meningococcal vaccine, and Haemophilus influenzae type b (Hib) Any missing vaccinations may be administered starting with the Screening Period and during the trial following the initiation of AG-348 dosing as necessary according to recommended vaccination guidance.
- •10. ECOG Performance Status = 2
- •11.Patients must be taking at least 1 mg of folic acid daily for at least 21 days prior to first dose and continued daily during study participation
- •12.Adequate organ function, defined as:
- •a.Serum AST and ALT = 2.5 × upper limit of normal (ULN) (unless the increased AST is assessed by the Investigator as due to hemolysis)
- •b.Normal or elevated levels of serum bilirubin. In patients with serum bilirubin > ULN, the elevation must be attributed to hemolysis with or without Gilbert's syndrome and must not be choledocholithiasis, cholecystitis, biliary obstruction, or hepatocellular disease
- •c.Serum creatinine = 1.25 × ULN. If serum creatinine > 1.25 × ULN, then 24 hour measured or calculated (Cockcroft-Gault) glomerular filtration rate (GFR) = 60 mL/min
- •d.Absolute neutrophil count (ANC) > 1.0 × 109/L
- •e.Platelet count = 100 × 109/L
- •f.Activated partial thromboplastin time (aPTT) and international normalized ratio (INR) = 1.25 × ULN, unless the patient is receiving therapeutic anticoagulants
排除标准
- •Core Period:
- •1.Hemoglobin level > 12.0 g/dL if male; Hb > 11.0 g/dL if female.
- •2.Additional diagnosis of any other congenital or acquired blood
- •disorder, including glucose-6-phosphate-dehydrogenase (G6PD)
- •deficiency, or any other hemolytic anemia process except for mild
- •alloimmunization
- •as a consequence of transfusion therapy.
- •3.Iron overload (hemosiderosis or concurrent hemochromatosis)
- •sufficiently severe to result in a clinical diagnosis by the Investigator of
- •cardiac, hepatic, or pancreatic insufficiency.
- •4.Prior bone marrow or stem cell transplant.
- •5.Clinically symptomatic cholelithiasis or cholecystitis. (Prior
- •cholecystectomy is not exclusionary. Patients with symptomatic
- •cholelithiasis or cholecystitis may be rescreened once the disorder has
- •been treated and clinical symptoms have resolved.)
- •6.Currently enrolled in another therapeutic clinical trial involving
- •therapy with any investigational or marketed product or placebo.
- •Concurrent participation in the Pyruvate Kinase Deficiency Natural
- •History Study (NCT02053480) is permitted.
- •7.Exposure to any investigational drug, device, or procedure within 28
- •days prior to Screening or trial participation.
- •8.Concurrent medical condition that could compromise participation in
- •the study such as:
- •a.Poorly controlled hypertension (defined as systolic blood pressure (BP)
- •> 150 mm Hg or diastolic BP > 90 mm Hg) refractory to medical
- •management.
- •b.History of recent (within < 6 months from Screening date) congestive
- •heart failure; myocardial infarction or unstable angina pectoris; or
- •hemorrhagic, embolic, or thrombotic stroke; deep venous thrombosis; or pulmonary or arterial embolism.
- •c.Currently active infection requiring the use of parenteral anti-microbial
- •agents or that is . Grade 3 (CTCAEv4.03) within 6 months of first dose.
- •d.A pattern or frequency of post-splenectomy sepsis that in the
- •assessment of the Investigator could reasonably be expected to interfere
- •with the ability of the patient to complete the 24 week Core Period study
- •participation.
- •e.Positive test for hepatitis B surface antigen (HBsAg) or hepatitis C
- •virus (HCV) antibody with signs of active Hepatitis B or C virus infection.
- •f.Positive test for human immunodeficiency virus (HIV) 1 or 2 antibody.
- •g.Diabetes mellitus judged to be in poor control by the Investigator or
- •requiring > 3 anti-diabetic agents counting insulin; use of insulin per se
- •is not exclusionary.
- •h.History of any primary malignancy with the exception of: curatively
- •treated non-melanomatous skin cancer; curatively treated cervical or
- •breast carcinoma in situ; or other primary tumor treated with curative
- •intent and no known active disease present and no treatment
- •administered during the last 3 years.
- •9.Undergone major surgery within 6 months of first dose.
- •10.Current or recent history of psychiatric disorder that in the opinion of
- •the Investigator or Medical Monitor could compromise the ability of the
- •patient to cooperate with study visits and procedures.
- 另有 8 项未显示
研究者
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