A Phase 2 Open Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Dose Levels of Subcutaneously Administered ELX-02 in Patients With Cystic Fibrosis With at Least One G542X Allele
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 10
- 主要终点
- Peak observed plasma concentration (Cpeak) over time
研究概览
简要总结
This is a Phase 2 open-label, dose-escalation study to evaluate the safety, tolerability, PK, and PD of multiple dose levels of SC administered ELX-02 with and without ivacaftor in patients with CF with at least one G542X allele.
In total, up to 16 patients will be enrolled in the trial; up to 4 patients will be homozygotes for G542X, and the remaining patients will be compound heterozygotes with one G542X or phenotypically similar nonsense allele and any Class 1 or Class 2 mutation.
Each patient will receive up to 5 escalating doses as follows:
- ELX-02 0.3 mg/kg per day SC
- ELX-02 0.75 mg/kg per day SC
- ELX-02 1.5 mg/kg per day SC
- An individualized dose of ELX-02, as high as 3.0 mg/kg per day SC, based on the patients observed safety and tolerability, PK at previous doses and the results of laboratory tests.
- ELX-02 1.5 mg/kg per day SC plus 150 mg ivacaftor every 12 bid
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females age 18 years and above
- •A confirmed diagnosis of nmCF with a documented G542X mutation, homozygote, or compound heterozygote with one of the specified mutations. For heterozygotes, one mutation has to be G542X or phenotypically similar nonsense allele, and the second mutation has to be any Class 1 or Class 2 mutation. Patients with one G542X allele or phenotypically similar nonsense allele and a second allele that is not a Class 1 or Class 2 mutation may be potentially allowed but only after discussion on a case by case basis with and written approval from the Sponsor.
- •Documented SCC ≥60 mEq
- •FEV1 ≥40% predicted normal for age, gender and height at Screening (Knudson Equation)
- •Body mass index (BMI) of 19.0 to 30.0 kg/m2 (inclusive). Patients with a lower BMI may be entered into the study at the discretion of the investigator following consultation with the Sponsor.
排除标准
- •Participation in clinical study including administration of any investigational drug or device in the last 30 days or 5 half-lives (whichever is longer) prior to investigational product dosing in the current study
- •History of any organ transplantation
- •Major surgery within 180 days (6 months) of Screening
- •Patients without documented prior aminoglycoside exposure who have a mitochondrial mutation that has been shown to increase sensitivity to aminoglycosides
- •Known allergy to any aminoglycoside
- •Patients with any abnormality at ENT screening, that indicates the presence of a vestibular toxicity associated with prior exposure to aminoglycosides.
- •Dizziness Handicap Inventory (DHI)-H score at screening must be >
- •Patients receiving CFTR modulators within 2 months of study treatment
研究组 & 干预措施
ELX-02
Eukaryotic ribosomal selective glycoside (ERSG)
干预措施: ELX-02 (Drug)
ELX-02
Eukaryotic ribosomal selective glycoside (ERSG)
干预措施: Ivacaftor (Drug)
结局指标
主要结局
Peak observed plasma concentration (Cpeak) over time
时间窗: Days 1, 2, and 7 of treatment periods 1-3; Days 1, 2, 7, and 14 of treatment period 4, sparse blood sampling at 30 min and 1 hour post dose
AEs associated with different dose levels of ELX-02
时间窗: From the time of first dosing through the follow-up visit, an average of approximately 9 weeks
Area under the plasma concentration curve from time zero to 24 hours (AUC0-24h)
时间窗: Day 1 of treatment periods 1, 2, 3, and 4
Full PK profile 8 blood samples over 24 hours
Trough observed plasma concentration (Cpredose) over time
时间窗: Days 1, 2 and 7 of treatment periods 1-3, Days 1, 2, 7 and 14 of treatment period 4, sparse sampling at pre-dose
Maximum observed plasma concentration (Cmax) on Day 1
时间窗: Day 1 of treatment periods 1, 2, 3, and 4
Full PK profile 8 blood samples over 24 hours
次要结局
- Changes from baseline in percent predicted forced expiratory flow at 25-75% (ppFEF25-75)(From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4)
- Changes from baseline in percent predicted forced expiratory volume (ppFEV1)(From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4)
- Changes from baseline in sweat chloride concentration(From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4)
- Changes from baseline in percent predicted forced vital capacity (ppFVC)(From baseline to Day 7 of treatment periods 1-3, and Days 7 and 14 of treatment period 4)