NCT02035605已完成1 期
A Phase 1 Single-ascending and Multiple-ascending Dose, Safety, Tolerability and Pharmacokinetics Study of Subcutaneously Administered ALN-AT3SC in Healthy Adult Volunteers and Hemophilia A or B Patients (Moderate or Severe Hemophilia)
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanofi
- 入组人数
- 51
- 试验地点
- 1
- 主要终点
- The safety of ALN-AT3SC evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), and AEs leading to study drug discontinuation.
研究概览
简要总结
The purpose of this study is to determine the safety, tolerability, and pharmacokinetics of ALN-AT3SC in healthy volunteers and Hemophilia A or B patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Part A (SAD phase) inclusion:
- •Healthy adult males aged 18 to 40 years inclusive at Screening.
- •Subjects with adequate complete blood counts and liver function tests.
- •Willing to provide written informed consent and willing to comply with study requirements.
- •Part B & C (MAD & MD phase) inclusion:
- •Adult male hemophilia patients aged 18 to 65 years inclusive at Screening.
- •Patients with adequate complete blood counts and liver function tests.
- •Patients with moderate or severe, clinically stable hemophilia A or B (Factor VIII or Factor IX ≤5%).
- •Willing to provide written informed consent and willing to comply with study requirements
- •Part D (MD Phase in patients with inhibitors) Inclusion:
- •Same as Parts B/C
- •A Bethesda inhibitor assay > 0.6 BU/mL
排除标准
- •Part A (SAD phase) exclusion:
- •Subjects with a personal history and/or family history of venous thromboembolism (VTE)
- •Subjects with a known co-existing thrombophilic disorder
- •Subjects with a history of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
- •Subjects with a history of serious mental illness that includes, but is not limited to schizophrenia, bipolar disorder, severe depression requiring hospitalization or pharmacological intervention.
- •Subjects who have a clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, renal, hematological, lymphatic, neurological, musculoskeletal, genitourinary, immunological including osteoarthritis and other inflammatory diseases, dermatological including rash, eczema, dermatitis, or connective tissue diseases or disorders.
- •Part B & C (MAD & MD phase) exclusion:
- •Patients with a current serious mental illness that, in the judgment of the Investigator, may compromise patient safety, ability to participate in all study assessments, or study integrity.
- •Patients who have a clinically relevant history or presence of cardiovascular, respiratory, gastrointestinal, renal, neurological, inflammatory or other diseases that in the judgment of the investigator precludes their participation in the study.
- •Patients with a known co-existing thrombophilic disorder
- •Patients with a history of multiple drug allergies or history of allergic reaction to an oligonucleotide or GalNAc.
- •Patients who are known to be HIV positive and have a CD4 count <400 cells/μL
- •Part D (MD Phase in patients with inhibitors) exclusion:
- •Same as Parts B/C
- •Patients who are known to be HIV positive and have a CD4 count <200 cells/μL
研究组 & 干预措施
ALN-AT3SC
Active Comparator
干预措施: ALN-AT3SC (Drug)
Sterile Normal Saline (0.9% NaCl)
Placebo Comparator
干预措施: Sterile Normal Saline (0.9% NaCl) (Drug)
结局指标
主要结局
The safety of ALN-AT3SC evaluated by the proportion of subjects experiencing adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicities (DLTs), and AEs leading to study drug discontinuation.
时间窗: Part A (SAD phase): through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112
次要结局
- The pharmacodynamic (PD) effect of ALN-AT3SC, evaluated by Plasma AT levels.(Part A (SAD) phase: through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112)
- The pharmacodynamic (PD) effect of ALN-AT3SC, evaluated by Plasma TG.(Part A (SAD) phase: through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112)
- The pharmacokinetics (PK) of ALN-AT3SC as characterized by plasma PK profiles and urine samples.(Part A (SAD) phase: through day 56; Part B (MAD) phase: through Day 70; Part C (MD Phase) through Day 112; Part D (MD Phase in patients with inhibitors) through Day 112)
研究者
研究点 (1)
Loading locations...
相似试验
招募中
1 期
A Study to Investigate ALE.P02 as Monotherapy in Adult Patients With Selected CLDN1+ Solid TumorsSquamous Non-small-cell Lung CancerHead and Neck Squamous Cell CarcinomaEsophageal Squamous Cell CarcinomaCervical Squamous Cell CarcinomaNCT06747585Alentis Therapeutics AG170
终止
1 期
A Study of ALN-HSD in Healthy Adult Subjects and Adult Patients With Nonalcoholic Steatohepatitis (NASH)Nonalcoholic SteatohepatitisNASHNCT04565717Alnylam Pharmaceuticals6
招募中
1 期
A Study to Evaluate ALN-BCAT in Patients With Hepatocellular CarcinomaAdvanced Hepatocellular CarcinomaMetastatic Hepatocellular CarcinomaNCT06600321Alnylam Pharmaceuticals158
已完成
1 期
Safety Tolerability and Pharmacokinetics of ALD403Migraine DisordersNCT01579383Alder Biopharmaceuticals, Inc.104
终止
1 期
A Three-part Study to Determine the Safety, Tolerability and Pharmacokinetics of GSK1322322 in Healthy Volunteers and Healthy Male Japanese SubjectsInfections, BacterialNCT01818011GlaxoSmithKline12