A Seamless Phase I/II Trial With an Initial Open-label Dose Escalation Part and a Subsequent Randomised, Double-blind, Placebo-controlled Expansion Part to Evaluate the Safety, Tolerability, and Efficacy of a Single Dose of BI 3720931, an Inhaled Lentiviral Vector Gene Therapy, in Adult People With Cystic Fibrosis Who Are Ineligible for CFTR Modulators (Lenticlair 1)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 8
- 主要终点
- Phase I: Occurrence of any drug-related, treatment-emergent adverse events (AE) up to Week 24 after drug administration
研究概览
简要总结
This study is open to adult men with cystic fibrosis and adult women with cystic fibrosis who cannot have children. People with cystic fibrosis can join if they are not eligible to receive cystic fibrosis transmembrane conductance regulator modulator therapy (CFTR-MT). The purpose of this study is to find out how well a medicine called BI 3720931 is tolerated and whether it improves lung function in people with cystic fibrosis. In this study, BI 3720931 is given to humans for the first time.
This study has two phases. In Phase 1, participants are put in one of 3 groups, one group after the other. Each group gets a different dose of BI 3720931. Group 1 starts with the lowest dose, followed by group 2 with the middle and group 3 with the high dose. In Phase 2, participants are put into 3 groups by chance, but at the same time. 2 groups get different doses of BI 3720931 selected based on results of Phase 1, and 1 group gets placebo. All study participants get only 1 dose of BI 3720931 or placebo and they use a special inhaler to take the study medicine. The placebo inhaler looks like the BI 3720931 inhaler but does not contain any medicine. During the study, participants continue taking their usual medicines.
Doctors closely monitor participants' health at the study site for the first 3 days after receiving BI 3720931. Participants visit their doctors regularly thereafter. The doctors check the health of the participants and note any health problems that could have been caused by BI 3720931. Study participants regularly do a standard lung function test to measure how well their lungs are working. Participants, in either Phase 1 or Phase 2, are in the study for 7 months. After completion of this study, participants will take part in a long-term follow-up study (1504-0003).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Phase I: open-label Phase II: double-blind
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
- •Cystic fibrosis (CF)-pulmonary phenotype and a confirmed diagnosis of CF:
- •Positive sweat chloride ≥60 mmol/L by pilocarpine iontophoresis OR
- •Genotype with 2 identifiable CF-causing mutations accompanied by one or more clinical features if sweat chloride testing is between 30 and 59 mmol/L
- •Trial participants who are not eligible for treatment with cystic fibrosis transmembrane conductance regulator modulator therapy (CFTRmt) due to their genotype with 2 identified CFTR-mutations (including Class I CFTR gene mutations) and are also not expected to become eligible during the trial according to investigator´s opinion
- •Trial participants able to perform acceptable spirometric maneuvers according to American Thoracic Society/European Respiratory Society 2019 standards
- •Forced expiratory volume in 1 second, percent of predicted value (FEV1pp) ≥50% and ≤100% of predicted normal at Visit
- •Predicted value based on Global Lung Initiative lung function reference equations
- •Stable CF disease with no pulmonary exacerbation 4 weeks prior to the screening visit and during the screening period and stable drug- and non-drug therapy for CF in the 4 weeks prior to dosing Further inclusion criteria apply.
排除标准
- •Trial participants not eligible for CFTRmt based on contraindications (e.g. liver failure) or who needed to withdraw CFTRmt due to intolerability are not appropriate candidates for this Phase I/II trial
- •Trial participants requiring chronic use of systemic corticosteroids or immunosuppressants to treat another condition Further exclusion criteria apply.
研究组 & 干预措施
Phase I: Dose group 1 (low dose)
干预措施: BI 3720931 (Genetic)
Phase I: Dose group 1 (low dose)
干预措施: Inhaler (Device)
Phase I: Dose group 2 (medium dose)
干预措施: BI 3720931 (Genetic)
Phase II: Dose group 1
干预措施: BI 3720931 (Genetic)
Phase II: Dose group 2
干预措施: Inhaler (Device)
Phase I: Dose group 3 (high dose)
干预措施: Inhaler (Device)
Phase I: Dose group 2 (medium dose)
干预措施: Inhaler (Device)
Phase II: Placebo group
干预措施: Placebo (Drug)
Phase II: Dose group 1
干预措施: Inhaler (Device)
Phase II: Placebo group
干预措施: Inhaler (Device)
Phase I: Dose group 3 (high dose)
干预措施: BI 3720931 (Genetic)
Phase II: Dose group 2
干预措施: BI 3720931 (Genetic)
结局指标
主要结局
Phase I: Occurrence of any drug-related, treatment-emergent adverse events (AE) up to Week 24 after drug administration
时间窗: up to 24 weeks
Phase II: Absolute change from baseline in forced expiratory volume in 1 second, percent of predicted value (FEV1pp) at Week 8 after drug administration
时间窗: at baseline, at week 8
次要结局
- Phase I: Absolute change from baseline in FEV1pp at Week 24 after drug administration(at baseline, at week 24)
- Phase II: Occurrence of any drug-related, treatment-emergent AEs up to Week 24 after drug administration(up to 24 weeks)
- Phase I: Occurrence of treatment response defined as change from baseline ≥5% in FEV1pp, comparing the mean of 3 pre-treatment FEV1pp measured in the screening period with the mean of 3 post-treatment FEV1pp-values at Weeks 4, 6, and 8(up to 12 weeks)
- Phase I: Occurrence of any dose limiting toxicities (DLTs) up to Week 24 after drug administration(up to 24 weeks)
- Phase II: Absolute change from baseline in FEV1pp at Week 24 after drug administration(at baseline, at week 24)
- Phase II: Occurrence of any serious adverse events (SAEs) up to Week 24 after drug administration(up to 24 weeks)