A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study toDetermine the Safety and Efficacy of a Single Dose of ASN100 forthe Prevention of Staphylococcus aureus Pneumonia in HeavilyColonized, Mechanically Ventilated Subjects
试验速览
- 阶段
- 2 期
- 状态
- Other
- 发起方
- Arsanis Inc
- 入组人数
- 354
- 试验地点
- 4
- 主要终点
- Proportion of subjects in MITT population who develop S. aureus pneumonia
研究概览
简要总结
This is a double-blind, randomized, single-dose, placebo-controlled study of ASN100 for the prevention of S. aureus pneumonia in mechanically ventilated subjects who are heavily colonized with S. aureus. This will be a global study conducted at approximately 70 sites. Subjects will be screened for eligibility; once an Informed Consent Form (ICF) is signed and all entry criteria are met, a subject is considered to be enrolled in the study. All enrolled subjects will undergo an observational stage evaluating endotracheal colonization. Subjects who are randomized will undergo a treatment, monitoring, and follow-up period. Approximately 2250 eligible subjects who meet all of the inclusion criteria and none of the exclusion criteria will be screened daily (while mechanically ventilated) for up to 8 days to identify those subjects who are heavily colonized with S. aureus. Upon determination of eligibility, approximately 354 subjects will be randomized in a 1:1 ratio to 1 of 2 treatment groups i.e ASN 100 or placebo. The primary objective of this study is to evaluate the safety, tolerability, and efficacy of a single dose of ASN100 (administered as ASN-1 and ASN-2 components) versus placebo for the prevention of S. aureus pneumonia in mechanically ventilated subjects who are heavily colonized with S. aureus. The secondary objectives of this study are to compare the duration of mechanical ventilation, length of stay in the intensive care unit (ICU), determine the serum pharmacokinetics (PK), compare 28-day all-cause mortality post-treatment in subjects treated with ASN100 versus placebo.
Anindependent Data Review Committee (DRC) performed a pre-specifiedinterim futility analysis for Study ASN100-201. The reviewwas based on 118 randomized and treated subjects who reachedStudy Day 28, to capture the study visits at which the primary andsecondary outcome assessments are performed. The futility analysis wasconducted in one third of the planned sample size by the independent DRCand it was concluded that it would be futile to continue the study tocompletion. Therefore, the Sponsor, Arsanis, Inc., has decidedto terminate the clinical study based on the DRC recommendation of futility.The decision to terminate the study is based on the low probability of meetingthe primary efficacy endpoint and not based on an evaluation of the ASN100 safety.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Subject, legally authorized representative, or council of independent physicians (CIP) (if applicable) has provided written informed consent;
- •Subject is ≥18 years of age at the time of enrollment;
- •Subject is currently hospitalized and is mechanically ventilated endotracheally (i.e., orotracheal or nasotracheal) and, in the Investigator’s opinion, will require ongoing ventilator support for at least 48 hours; NOTE: Subjects with a tracheostomy at the time of enrollment are not eligible.
- •After enrollment, conversion to tracheostomy is permitted per standard of care.
- •Female subjects must not be pregnant or lactating.
- •Female subjects of childbearing potential must have a documented negative pregnancy test at the Screening Visit.
- •Female subjects may be enrolled on the basis of a negative urine pregnancy test, pending the result of a negative serum pregnancy test prior to randomization; and
- •Female subjects of childbearing potential and non-surgically sterile male subjects who are sexually active must agree to use an approved highly effective form of contraception from the time of informed consent until 165 days post-dose.
- •Approved forms of contraception include hormonal intrauterine devices, hormonal contraceptives (oral birth control pill, depo, patch, or injectable) together with supplementary double barrier methods such as condoms or diaphragms with spermicidal gel or foam.
- •NOTE: The following categories define women who are NOT considered to be of childbearing potential: • Premenopausal female with 1 of the following: o Documented hysterectomy, o Documented bilateral salpingectomy, or o Documented bilateral oophorectomy, or • Postmenopausal female, defined as having amenorrhea for at least 12 months without an alternative medical cause.
排除标准
- •Subject has received intravenous (IV) immunoglobulin therapy within 4 months prior to the Screening Visit;
- •Subject has a chest X-ray or thoracic computed tomography (CT) scan that is definitive for a diagnosis of pneumonia;
- •Subject demonstrates both of the following: a.
- •Need for acute changes in ventilator support to enhance oxygenation or to the amount of positive end-expiratory pressure; AND NOTE: Changes made in ventilator support due to day-to-day maintenance other than those changes made to improve oxygenation will not exclude a subject from participation in the study.
- •New onset of purulent suctioned respiratory secretions;
- •Subject has a known and documented ETA culture showing heavy colonization with a Gram-negative organism at enrollment or at any time during the Screening period; NOTE: Randomization should not be delayed while waiting for Gram-negative results if heavy colonization with S.
- •aureus has been confirmed.
- •Subject has been diagnosed with neutropenia (absolute neutrophil count <500/mm3);
- •Subject has a severe non-pulmonary source of infection which, in the Investigator’s opinion, would interfere with the conduct of the study or jeopardize the subject’s safety;
- •Subject is currently on either continuous veno-venous hemodialysis or extracorporeal membrane oxygenation;
- •Subject has been previously exposed to ASN100 or ASN-1 or ASN-2, individually;
- •Subject has a known hypersensitivity to ASN100 or any of its excipients;
- •Subject has received any investigational product within 30 days prior to the Screening Visit (or 5 half-lives of the investigational product, whichever is longer);
- •Subject has, in the opinion of the Investigator, a high probability of death within 72 hours of enrollment;
- •Subject is, in the opinion of the Investigator, not able or willing to comply with the protocol;
- •Any condition that, in the opinion of the Investigator, would compromise the safety of the subject, the potential activity of the study drug, or the quality of the data; or
- •Subjects with a known history or current (suspected) diagnosis of cytokine release syndrome associated with the administration of peptides, proteins, and/or antibodies.20 NOTE: Subjects with a prior history of sepsis are not excluded.
结局指标
主要结局
Proportion of subjects in MITT population who develop S. aureus pneumonia
时间窗: Up to day 22
次要结局
- Duration of mechanical ventilation(21 day)
- Length of ICU stay(21 days)
- All cause mortality(28 days)