LBCTR2019090195已完成2 期
A Phase 2a, Open-label, Single and Multiple Dose Study to Evaluate the Pharmacokinetics, Safety, Tolerability, and Exploratory Treatment Effect of GBT440 in Pediatric Participants With Sickle Cell Disease
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 38
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
- 分配方式
- N/a: Single Arm Study
- 主要目的
- Treatment
- 盲法
- Open (masking not used)
入排标准
- 年龄范围
- 0 至 17（—）
- 性别
- All
入选标准
- •1. Male or female participants with homozygous hemoglobin SS (HbSS) or hemoglobin S beta0 thalassemia (HbS ß0 thal).
- •Part A – 6 to 17 years of age (Cohort 1 [12 to 17] and Cohort 2 [6 to 11] as defined in the Study Design)
- •Part B – 12 to 17 years of age
- •Part C – 4 to 17 years of age
- •Part D – 6 months to < 4 years of age
- •3. Hydroxyurea (HU) therapy:
- •Parts A, B, and C – A participant taking HU may be enrolled if the dose has been stable for at least 3 months with no anticipated need for
- •dose adjustments during the study and no sign of hematological toxicity.
- •Part D – A participant taking HU may be enrolled if the dose has been stable for at least 1 month. Titration to the maximum tolerated dose
- •(MTD) is allowed during the study.
- •4. Hemoglobin (Hb):
- •Part A – No restriction
- •Part B – Hb = 10.5 g/dL
- •Part C – Hb = 10.5 g/dL
- •Part D – Hb = 10.5 g/dL
- •5. Written informed parental/guardian consent and participant assent has been obtained per institutional review board (IRB)/Ethics Committee
- •(EC) policy and requirements, consistent with ICH guidelines.
- •6. Participants in Part B (only) of the study must complete a minimum of 14 days with ePRO to be enrolled. Investigator discretion will be used
- •to determine if a participant who has previously been screen failed due to a lack of baseline ePRO data collection can be invited back for rescreening.
- •7. If sexually active and female, must agree to abstain from sexual intercourse or to use a highly effective method of contraception throughout
- •the study period and for 30 days after discontinuation of study drug. If sexually active and male, must agree to abstain from sexual intercourse
- •or willing to use barrier methods of contraception throughout the study period and for 30 days after discontinuation of study drug.
- •8. Females of child-bearing potential are required to have a negative pregnancy test before the administration of study drug.
- •9. Sufficient venous access to permit collection of PK samples and monitoring of laboratory safety variables, in the opinion of the Investigator.
- •10. For Part C only, participants 12 to 17 years of age must have a TCD velocity = 140 cm/sec by nonimaging TCD or = 125 cm/sec by TCDi
- •measured anytime during screening.
排除标准
- •1. Any one of the following requiring medical attention within 14 days prior to signing the informed consent form (ICF):
- •Vaso-occlusive crisis (VOC)
- •Acute chest syndrome (ACS)
- •Splenic sequestration crisis
- •Dactylitis
- •2. Requires chronic transfusion therapy.
- •3. History of stroke or meeting criteria for primary stroke prophylaxis (history of two TCD measurements = 200 cm/sec by nonimaging TCD or =
- •185 cm/sec by TCDi).
- •For the potential modification, addition of approximately 20 participants enrolled in Part C, TCD = 170 cm/sec by nonimaging TCD or = 155
- •cm/sec by TCDi.
- •4. Transfusion within 30 days prior to signing the ICF.
- •5. Renal dysfunction requiring chronic dialysis or creatinine = 1.5 mg/dL.
- •6. Hepatic dysfunction characterized by alanine aminotransferase (ALT) > 4× upper limit of normal (ULN) for age.
- •7. Clinically relevant cardiac abnormality, in the opinion of the Investigator, such as:
- •Hemodynamically significant heart disease, eg, congenital heart defect, uncompensated heart failure, or any unstable cardiac condition
- •An arrhythmic heart condition requiring medical therapy
- •8. QTcF > 450 msec, congenital long QT syndrome, second or third degree heart block at rest (with the exception of asymptomatic Mobitz type
- •I second degree heart block).
- •9. Received an investigational drug within 30 days or 5 half-lives, whichever is longer, of signing the ICF.
- •10. Heavy smoker (defined as smoking more than 10 cigarettes/day or its nicotine equivalent including e-cigarettes).
- •11. Unlikely to comply with the study procedures.
- •12. Other medical, psychological, or addictive condition that, in the opinion of the Investigator, would confound or interfere with evaluation of
- •safety and/or PK of the investigational drug, prevent compliance with the study protocol, or preclude informed consent.
- •13. Participants who do not have a TCD window (Part B and C only) (ie, participants who are unable to have a TCD due to skull ossification).
- •14. For Part C only, prior participation in Part B.
- •15. Active symptomatic COVID-19 infection.
- •In addition, for Part D only:
- •16. Body weight < 5 kg for 1 month prior to the screening visit and at the screening visit.
- •17. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is
- •acceptable).
- •18. History of malignancy within the past 2 years prior to treatment Day 1 requiring chemotherapy and/or radiation (with the exception of local
- •therapy for non-melanoma skin malignancy).
- •19. Clinically significant bacterial, fungal, parasitic, or viral infection currently receiving or that will require therapy.
- •Participants with acute bacterial infection requiring antibiotic use should delay screening until the course of antibiotic therapy has been
- •completed and the infection has resolved, in the opinion of the investigator.
- •Known active hepatitis A, B, or C infection or human immunodeficiency virus (HIV)-positive.
- •Known active malaria.
研究者
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