Phase 1, Open-Label, Single Ascending Dose and Multiple Dose Study to Assess Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneously Administered AIR-001 in Adults With AATD Due to PiZZ Genotype
概览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- AIRNA Corporation
- 入组人数
- 54
- 试验地点
- 4
- 主要终点
- Number of participants with treatment-emergent adverse events (TEAEs)
概览
简要总结
This is a Phase 1, open-label, single ascending dose (SAD) and multiple dose (MD) study of AIR-001 in participants with alpha-1 antitrypsin deficiency (AATD) due to PiZZ genotype.
详细描述
The study is designed to evaluate the safety, tolerability, PK, and PD of AIR-001.
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 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants \>18 years and \<75 years of age at the time of signing informed consent
- •Total serum AAT levels \< 11µM (57 mg/dL)
- •Pi\*ZZ genotype confirmed by DNA sequencing within the SERPINA1 gene with no known co-occurring SERPINA1 null variants
- •Spirometry: Forced expiratory volume in 1 second (FEV1) ≥ 40% of predicted
- •Non-smoker, including vaping, for at least 6 months prior to screening
- •Body mass index between 18-33.0 kg/m²
- •Body weight ≥ 45 kg and ≤110 kg
- •Willing and able to give written informed consent prior to the initiation of any study procedure by the participant
- •Negative beta human chorionic gonadotropin (β-hCG) at enrolment for women of childbearing potential (WOCBP) only.
- •Participants who are either a WOCBP or male participant who is heterosexually active with a WOCBP must consent to use a highly effective method of contraception from screening visit until at least 4 weeks after the last dose of investigational medicinal product (IMP).
排除标准
- •Female participants who are nursing or lactating
- •Participant has received AAT augmentation therapy within 30 days prior to Screening Visit or plans to receive AAT augmentation therapy at any time during study participation.
- •Known or suspected allergy or intolerance to AIR-001 or its components
- •Acute respiratory tract infection or clinically-diagnosed chronic obstructive pulmonary disease (COPD) exacerbation that required antibiotic treatment and/or systemic corticosteroids within the 8 weeks prior to dosing.
- •Positive screening test for COVID-19 and/or Influenza.
- •Lung disease that requires use of continuous oral corticosteroids, continuous supplemental oxygen, day-time ventilatory support, or any participant who is on a lung transplant waiting list.
- •Liver Fibrosis score \> 10 kPa defined by screening liver elastography, historical liver biopsy showing ≥ F3 fibrosis (METAVIR or comparable scoring system), or established diagnosis of hepatic cirrhosis.
- •Any of the following screening laboratory abnormalities:
- •Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or gamma-glutamyl transferase (GGT) \> 3 x upper limit of normal (ULN)
- •Total bilirubin \> ULN (note: for participants with documented Gilbert's syndrome and direct bilirubin ≤ ULN , exclusion criterion is total bilirubin is \> 2.5 mg/dL)
研究组 & 干预措施
AIR-001 SAD Cohort 4
AIR-001 administered by SC injection, single dose.
干预措施: AIR-001 SAD dose level 4 (Drug)
AIR-001 SAD Cohort 1
AIR-001 is an RNA-editing oligonucleotide in sterile preservative-free solution administered by subcutaneous (SC) injection as a single dose.
干预措施: AIR-001 SAD dose level 1 (Drug)
AIR-001 MD Cohort 4
AIR-001 administered by SC injection as multiple doses.
干预措施: AIR-001 MD dose level 4 (Drug)
AIR-001 MD Cohort 5
AIR-001 administered by SC injection as multiple doses.
干预措施: AIR-001 MD dose level 5 (Drug)
AIR-001 MD Cohort 1
AIR-001 is an RNA-editing oligonucleotide in sterile preservative-free solution administered by subcutaneous (SC) injection as multiple doses.
干预措施: AIR-001 MD dose level 1 (Drug)
AIR-001 MD Cohort 3
AIR-001 administered by SC injection as multiple doses.
干预措施: AIR-001 MD dose level 3 (Drug)
AIR-001 MD Cohort 6
AIR-001 administered by SC injection as multiple doses.
干预措施: AIR-001 MD dose level 6 (Drug)
AIR-001 MD Cohort 2
AIR-001 administered by SC injection as multiple doses.
干预措施: AIR-001 MD dose level 2 (Drug)
AIR-001 SAD Cohort 2
AIR-001 administered by SC injection as a single dose.
干预措施: AIR-001 SAD dose level 2 (Drug)
AIR-001 SAD Cohort 3
AIR-001 administered by SC injection as a single dose.
干预措施: AIR-001 SAD dose level 3 (Drug)
结局指标
主要结局
Number of participants with treatment-emergent adverse events (TEAEs)
时间窗: Up to Day 169
Incidence of laboratory abnormalities and shifts from baseline, including hematology, chemistry, coagulation, and urinalysis parameters
时间窗: Baseline through up to Day 169
Incidence of abnormal vital signs
时间窗: Baseline through up to Day 169
Incidence of abnormal electrocardiogram (ECG) findings
时间窗: Baseline through up to Day 169
次要结局
- Area under the plasma concentration time curve for AIR-001 from time of dosing to the last measurable concentration (AUClast)(Up to Day 169)
- Maximum concentration of AIR-001 in plasma (Cmax)(Up to Day 169)
- Change from baseline in levels of total serum AAT protein, including serum M-AAT, Z-AAT, and functional AAT protein(Up to Day 169)