An Open-label, Phase 1/2 Trial of Gene Therapy 4D-710 in Adults With Cystic Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 37
- 主要终点
- Incidence and severity of adverse events
研究概览
简要总结
This is a Phase 1/2 multicenter, open-label, single dose trial of 4D-710 investigational gene therapy in adults with cystic fibrosis.
详细描述
This Phase 1/2 trial will evaluate the safety, tolerability, and preliminary efficacy of 4D-710, an investigational gene therapy, in adults with cystic fibrosis (CF) lung disease who are ineligible or unable to tolerate CFTR modulator therapy. A sub-study will evaluate 4D-710 in a cohort of adults with CF advanced lung disease and/or frequent pulmonary exacerbation (PE) while on currently available CFTR modulator therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •(Primary Study):
- •18 years and older
- •Confirmed diagnosis of cystic fibrosis (CF) and CF lung disease including:
- •Sweat chloride ≥ 60 mmol/L
- •Mutation Status
- •Bi-allelic mutations in the CFTR gene, or
- •Single mutation in the CFTR gene and clinical manifestations of CF lung disease
- •Ineligible for CFTR modulator therapy, or previously received modulator therapy but discontinued due to adverse effects.
- •Forced expiratory volume in 1 second (FEV1) ≥ 50% and ≤ 90% of predicted (per Global Lung Function Initiative) at Screening
- •Resting oxygen saturation ≥ 92% on room air at Screening
- •Key Inclusion Criteria (Sub-Study):
- •18 years and older
- •Confirmed diagnosis of cystic fibrosis (CF) and CF lung disease including:
- •Sweat chloride ≥ 60 mmol/L
- •Mutation Status
- •Bi-allelic mutations in the CFTR gene, or
- •Single mutation in the CFTR gene and clinical manifestations of CF lung disease
- •Currently on a stable dose of CFTR modulator therapy for a minimum of 60 days prior to Screening and agree to maintain current regimen through the 24-month Observation Period
- •FEV1 ≥ 40% and < 70% predicted (per Global Lung Function Initiative) at Screening, AND/OR experienced at least 2 pulmonary exacerbations in the last year requiring intravenous antibiotics
排除标准
- •(Primary and Sub Study):
- •Any prior gene therapy for any indication (Exception: mRNA-based or antisense oligonucleotide therapies are not exclusionary)
- •Active Mycobacterium abscessus infection requiring ongoing treatment at Screening
- •Active allergic bronchopulmonary aspergillosis requiring management with systemic corticosteroids or antifungal therapy
- •Smoking (e.g. cigarettes, cigars, cannabis) or use of a vaping product during the 2 months prior to screening; must agree to not smoke or use vaping products during Screening and initial 24-month observation period.
- •Contraindication to systemic corticosteroid therapy
- •Requires chronic use of systemic corticosteroids or immunosuppressants to treat another condition
- •If no known diagnosis of cystic fibrosis related diabetes (CFRD), Type I, or Type II diabetes: Hemoglobin A1C ≥ 6.5% at Screening
- •If known diagnosis of CFRD, Type I or Type II diabetes: Hemoglobin A1C > 7.5% at Screening
- •Recent history of symptomatic hyperglycemia or unstable blood glucose levels as per Investigator's assessment
- •Other conditions that, in the Investigator's opinion, may interfere with management of corticosteroid-related hyperglycemia
- •Body Mass Index (BMI) < 16
- •Laboratory abnormalities at screening:
- •ALT, AST or GGT ≥ 3 × the upper limit of normal (ULN)
- •Total bilirubin ≥ 2 × ULN
- •Hemoglobin < 10 g/dL
- •Requirement for continuous or night-time oxygen supplementation
- •Known CF liver disease with evidence of multilobular cirrhosis
- •History of thrombosis (excluding catheter-related thrombosis) or conditions associated with increased risk of thrombosis
研究组 & 干预措施
4D-710 Phase 1: Dose Exploration
Participants who are ineligible for or intolerant of modulator therapy will receive one of various dose levels of 4D-710 to identify recommended phase 2 dose(s) for further evaluation.
干预措施: 4D-710 (Biological)
4D-710 Phase 2: Dose Expansion
Participants will receive a single inhalational administration of 4D-710 at the dose level(s) selected for dose expansion.
干预措施: 4D-710 (Biological)
4D-710 Dose Exploration (Sub-Study)
Participants who are on currently available CFTR modulator therapy will receive a dose of 4D-710 at various dose levels.
干预措施: 4D-710 (Biological)
结局指标
主要结局
Incidence and severity of adverse events
时间窗: 60 Months
Safety and tolerability of 4D-710 following a single dose via inhalation, as assessed by incidence and severity of treatment emergent adverse events, serious adverse events, and dose limiting toxicities, including clinically significant changes from baseline to scheduled time points in safety parameters.
次要结局
未报告次要终点