2023-508138-33-00已完成1/2 期
Phase 1/2 Multicenter, Open-label Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NTLA-3001 in Participants with Alpha-1 Antitrypsin Deficiency (AATD)-Associated Lung Disease
Intellia Therapeutics Inc.1 个研究点 分布在 1 个国家目标入组 4 人开始时间: 2024年11月18日最近更新:
试验速览
- 阶段
- 1/2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 4
- 试验地点
- 1
- 主要终点
- 1. Treatment-emergent adverse events (TEAE).
研究概览
简要总结
To evaluate the safety and tolerability of NTLA-3001 following a single treatment in adult participants with AATD-associated lung disease
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •Male or female participants, 18 to 75 years of age inclusive, at the time of signing informed consent.
- •Participants must provide written informed consent before any protocol-specified assessment is performed.
- •Participants must agree to the alcohol consumption restrictions.
- •Participants must have a negative cotinine test and agree to the smoking and nicotine restrictions.
- •Diagnosis of AATD-associated lung disease meeting specific criteria.
- •Per Investigator assessment, the participant has either maximized or refused available standard of care. For participants on AAT augmentation therapy, the Investigator determines that it is clinically acceptable to hold augmentation therapy for at least 4 weeks prior to dosing and refrain from initiating augmentation therapy for at least 12 weeks postdosing. The Investigator will review the protocol with the participant, including temporary withholding of AAT augmentation therapy, and potential consequences.
- •No prior diagnosis of protein-losing enteropathy or nephropathy or history of hypoalbuminemia.
- •AAV TAb below the laboratory assay cut-off titer.
- •Participants must meet specific laboratory criteria.
- •aPTT, INR, fibrinogen and D-dimer within the reference range or clinically nonsignificant per Investigator assessment.
- •Male participants must agree to the contraceptive requirements and sperm donation restrictions.
- •Female participants must not be pregnant or breastfeeding and must agree to the contraceptive requirements and egg (ova, oocyte) restrictions.
排除标准
- •Impaired liver function.
- •History of active malignancy within 5 years prior to Screening or during the Screening period, except curatively resected basal cell or squamous cell carcinoma of skin.
- •Prior liver, heart, or other solid organ transplant; lung volume reduction surgery (LVRS); bone marrow transplant; or anticipated transplant or LVRS within 1 year of Screening. Note: Prior history of or planned corneal transplant is not exclusionary.
- •Prior receipt of any gene therapy.
- •Receiving an investigational intervention or participating in another clinical study within 30 days or within 5 half-lives of the drug prior to Screening. Note: Observational, non-interventional registry trials (studies with no procedural assessments) are acceptable.
- •Uncontrolled hypertension (systolic BP > 160 mmHg, diastolic BP > 100 mmHg) despite maximal medical treatment.
- •Participants who have known hypersensitivity to any LNP component (or its excipients) or formulation buffer used to suspend the viral vector, or contraindication to high-dose steroids.
- •Unable or unwilling to take the required pretreatment medication regimen or postinfusion corticosteroid regimen.
- •Participant is not considered suitable for study inclusion in the opinion of the Investigator for other reasons.
- •Any of the following within 12 months prior to Screening: (a) Myocardial infarction; (b) Transient ischemic attack; (c) Cerebrovascular accident; (d) Pulmonary embolism; (e) New York Health Association Class III or IV heart failure.
- •History of hepatitis B or C infection or positive hepatitis B surface antigen (HbsAg) or hepatitis C virus antibody (HCV Ab) test. Laboratory results confirmed at Day -
- •History of positive HIV status or positive HIV status at Screening. Laboratory results confirmed at Day -
- •Known or suspected systemic parasitic, fungal, or viral infection, including COVID-19, or received antibiotics for bacterial infection; vaccines within 14 days prior to Screening; live vaccines within 30 days prior to Screening. Status confirmed at Day -
- •Use of corticosteroids above 5 mg/day of prednisone (or equivalent) or other immunosuppressive medications within 4 weeks prior to Screening.
- •Have had a serious COPD exacerbation (as determined by the Investigator) or used antibiotics for a COPD exacerbation or respiratory infection within 4 weeks prior to Screening.
- •History of anaphylaxis or severe systemic reaction to AAT augmentation therapy, or immune response to AAT augmentation therapy as indicated by clinical history of an adverse immune response to infusion with decreased therapeutic effect in combination with documentation of serum anti-AAT antibodies.
- •History of alcohol or drug abuse within 3 years prior to Screening.
结局指标
主要结局
1. Treatment-emergent adverse events (TEAE).
1. Treatment-emergent adverse events (TEAE).
次要结局
- 1. PD. Circulating alpha-1 antitrypsin (AAT) protein.
- 2. PK. Plasma concentration-time profiles and PK parameters of the components of the study intervention.
- 3. Immunogenicity. Total antibodies (TAb) and neutralizing antibodies (NAb) to AAV.
- 4. Immunogenicity. Antibodies to AAT protein.
- 5. Immunogenicity. Anti-drug antibodies to LNP.
- 6. Immunogenicity. Anti-Cas9 protein antibodies.
- 7. Shedding (Phase 2 only). AAV VGCN per cell in blood, urine, saliva, and semen samples.
- 8. Exploratory. St George’s Respiratory Questionnaire & 36-item short form health survey questionnaire (SF-36).
研究者
Trial Manager at Intellia
Scientific
Intellia Therapeutics Inc.
研究点 (1)
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