Study to Evaluate Safety and Activity of Inhaled TRL1068 in Healthy Volunteers
A Phase 1, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Pharmacokinetics of Inhaled TRL1068 in Healthy Volunteers
調査の概要
詳細な説明
This is a Phase 1, double-blind study to assess the safety and PK of inhaled TRL1068. Healthy subjects aged 18-65, inclusive, will be screened. Subjects who meet all inclusion and no exclusion criteria will be enrolled into the study, assigned to a dose group (DG), and randomized to receive IP.
The single dose (SD) study (Study Part A) will enroll one dose group (DG) of 7 healthy participants (5 active and 2 placebo), with each participant receiving a single inhaled dose of TRL1068 or matching placebo [IP]. This DG will include a sentinel group of two participants (1 active and 1 placebo) who will be dosed at least 24 hours before the remaining five participants (4 active and 1 placebo). The remaining participants in a DG will only be dosed if no clinically significant safety or tolerability concerns are observed in the sentinel group, following review of the blinded safety data from the first two subjects in the DG by the PI and Sponsor. All participants in DG1 will be admitted to a Phase 1 research unit prior to the inhalation of IP on Day 1 and domiciled for 24 hours for observation.
The multiple dose (MD) study (Study Part B) will enroll one DG of 7 healthy participants (5 active and 2 placebo). Participants will receive inhaled doses of TRL1068 or matching placebo every other day for 7 days (on Days 1, 3, 5, and 7).
DGs will be enrolled sequentially with a safety review completed between DGs. A Study Monitoring Committee (SMC) will review all available safety data 48 hours after the last subject in a DG has completed the last dose prior to making a recommendation regarding escalation to the next higher DG.
研究の種類
入学 (推定)
段階
- フェーズ 1
連絡先と場所
研究連絡先
- 名前:Anton (Tony) Leighton, MD
- 電話番号:650-838-1400
- メール:clinicalstudies@trellisbio.com
研究連絡先のバックアップ
- 名前:Adriane Kisch-Hancock
- 電話番号:650-838-1400
- メール:AKisch-Hancock@trellisbio.com
研究場所
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Nebraska
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Lincoln、Nebraska、アメリカ、68502
- Celerion
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-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Healthy male and non-pregnant, non-breast-feeding female subjects at between 18 and 65 years of age, inclusive, and representative of the general population
- Normal spirometry at Screening, defined as FEV1 ≥ 80%
- Willing and able to provide written informed consent
- Availability for the entire duration of the study, and willingness to adhere to protocol requirements
- In good health, as determined by lack of clinically significant abnormalities in health assessments performed at the Screening Visit, as judged by the Principal Investigator (PI) or as delegated by the PI to a physician or nurse practitioner as sub-investigator
- Men and women of childbearing potential (WOCBP) must be willing to practice a highly effective method of contraception that may include, but is not limited to, abstinence, sex only with persons of the same sex, monogamous relationship with vasectomized partner, vasectomy, hysterectomy, bilateral tubal ligation, licensed hormonal methods, or intrauterine device (IUD) for 28 days before Screening and for 90 days after Day 1. Men must also refrain from donating sperm from Day 1 and for 90 days after Day 1.
Exclusion Criteria:
- Inability to tolerate blood draws or has poor venous access
- Body mass index (BMI) <18.5 or ≥35 kg/m2
- Clinically significant vital sign abnormalities (systolic blood pressure lower than 90 or over 160 mmHg; diastolic blood pressure lower than 50 or over 100 mmHg; or, heart rate less than 45 or over 100 bpm) at the Screening Visit
- Clinical diagnosis of acute or chronic viral or bacterial infection with the exception of chronic recurrent herpes simplex infection
ECG with clinically significant findings, including:
- Conduction disturbance (complete left or complete right bundle branch block or nonspecific intraventricular conduction disturbance with QRS ≥120 msec, PR interval ≥220 msec, any second- or third-degree atrioventricular block, or prolongation of the QT interval corrected according to Fridericia's correction [>450 msec male and >460 msec female])
- Significant repolarization (ST-segment or T-wave) abnormality; or
- Significant atrial or ventricular arrhythmia; or
- Frequent atrial or ventricular ectopy (e.g., frequent premature atrial contractions, 2 premature ventricular contractions in a row); or
- ST-elevation consistent with ischemia or evidence of past or evolving myocardial infarction
- Presence of any gastrointestinal pathology (e.g., chronic diarrhea, inflammatory bowel diseases), unresolved gastrointestinal symptoms (e.g., diarrhea, vomiting), or progressive liver or kidney disease
Significant abnormal safety labs, defined as:
- Greater than 30% outside of the normal range for any of the following: hemoglobin, white blood cell (WBC) count, platelet count, neutrophil count and blood urea nitrogen
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), direct bilirubin or indirect bilirubin >2 × the upper limit of normal
- Activated partial thromboplastin time (aPTT) prolongation >1.5 x ULN
- Renal function based on the, i.e., estimated creatinine clearance < 70 mL/min (Cockcroft-Gault formula using ideal body weight)
- Hemoglobin ≤ 128 g/L (males) and ≤ 115 g/L (females), and hematocrit ≤ 37% (males) and ≤ 32.0% for females
- Positive test results for HIV, Hepatitis B (HBsAg), or Hepatitis C (HCV) at the Screening Visit
- History of significant drug abuse within one year prior to the Screening Visit and/or ongoing
- History of significant alcohol abuse within one year prior to the Screening Visit defined as more than fourteen units of alcohol per week (one "unit" is equal to approximately ½ pint [200 mL] of beer, 1 small glass [100 mL] of wine, or 1 measure [25 mL] of spirits)
- Positive test for drugs of abuse, ETOH and nicotine (cotinine) at the Screening Visit
- Positive serum beta-human chorionic gonadotropin test for pregnancy, pregnant, or nursing women
- Unwilling to refrain from donating blood or plasma during the study
- Use of any new prescription medication or over-the-counter (OTC) product (including natural food supplements, vitamins, herbs) within 14 days prior to dosing
- Receipt of any vaccine or booster within 14 days prior to Day 1 or planned vaccination or booster within 4 weeks after IP administration
- Any planned medical intervention or personal event that might interfere with the ability to comply with the study requirements
- Is current study site staff paid entirely or partially by the contract for this trial, or staff who are supervised by the PI or sub-PI
- Receipt of an investigational product, or participation in another trial involving a marketed or investigational drug within 30 days of Day 1, or 5 half-lives of the investigational drug, whichever is longer
- Any other comorbidity or condition that, in the opinion of the Investigator would make the subject unsuitable for the study or unable to comply with the study requirements
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:ランダム化
- 介入モデル:順次割り当て
- マスキング:4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的:Single Dose
Randomized 5:2 (TRL1068:placebo) via inhalation.
Administered once on Day 1.
|
The IP will be in a solution for inhalation at a nominal concentration of 20 mg/mL.
The IP will be reconstituted with a formulation buffer to 10 mg/mL/PS20 0.055% and dosed at a fixed dose of 60 mg per dose (volume of 6 mL) to full completion.
Placebo will be normal saline.
This study will use a marketed nebulizer device, the Aerogen Solo™, which is designed to generate an aerosol to achieve effective levels of TRL1068 in distal airways.
|
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実験的:Multiple Dose
Randomized 5:2 (TRL1068:placebo) via inhalation.
Administered four times, on Days 1, 3, 5, and 7.
|
The IP will be in a solution for inhalation at a nominal concentration of 20 mg/mL.
The IP will be reconstituted with a formulation buffer to 10 mg/mL/PS20 0.055% and dosed at a fixed dose of 60 mg per dose (volume of 6 mL) to full completion.
Placebo will be normal saline.
This study will use a marketed nebulizer device, the Aerogen Solo™, which is designed to generate an aerosol to achieve effective levels of TRL1068 in distal airways.
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Incidence of abnormal physical exam findings
時間枠:30 days
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Clinically-significant abnormal physical exam findings will be reviewed
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30 days
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Severity of abnormal physical exam findings
時間枠:30 days
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Clinically-significant abnormal physical exam findings will be reviewed.
Severity scale used in this trial is Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (https://www.fda.gov/media/73679/download).
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30 days
|
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Incidence of abnormal serum chemistries and hematology
時間枠:30 days
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Clinically-significant abnormal laboratory results findings will be reviewed
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30 days
|
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Severity of abnormal serum chemistries and hematology
時間枠:30 days
|
Clinically-significant abnormal laboratory results findings will be reviewed.
Severity scale used in this trial is Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (https://www.fda.gov/media/73679/download).
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30 days
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Incidence of abnormal vital signs (temperature)
時間枠:30 days
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Clinically-significant abnormal temperatures will be reviewed
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30 days
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Severity of abnormal vital signs (temperature)
時間枠:30 days
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Clinically-significant abnormal temperatures will be reviewed
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30 days
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Incidence of abnormal vital signs (blood pressure)
時間枠:30 days
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Clinically-significant abnormal blood pressures will be reviewed
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30 days
|
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Severity of abnormal vital signs (blood pressure)
時間枠:30 days
|
Clinically-significant abnormal blood pressures will be reviewed
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30 days
|
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Incidence of abnormal vital signs (heart rate)
時間枠:30 days
|
Clinically-significant abnormal heart rates will be reviewed
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30 days
|
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Severity of abnormal vital signs (heart rate)
時間枠:30 days
|
Clinically-significant abnormal heart rates will be reviewed
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30 days
|
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Incidence and Severity of Adverse Events
時間枠:30 days
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reported AEs will be reviewed
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30 days
|
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Incidence of Serious Adverse Events
時間枠:30 days
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reported SAEs will be reviewed
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30 days
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Characterize the pharmacokinetics (PK) of inhaled TRL1068 overall and by DG (Cmax)
時間枠:8 days
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determined by ELISA
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8 days
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Characterize the pharmacokinetics (PK) of inhaled TRL1068 overall and by DG (Cmin)
時間枠:8 days
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determined by ELISA
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8 days
|
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Characterize the pharmacokinetics (PK) of inhaled TRL1068 overall and by DG (CL)
時間枠:8 days
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determined by ELISA
|
8 days
|
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Characterize the pharmacokinetics (PK) of inhaled TRL1068 overall and by DG (Vss)
時間枠:8 days
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determined by ELISA
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8 days
|
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Characterize the pharmacokinetics (PK) of inhaled TRL1068 overall and by DG (T1/2)
時間枠:8 days
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determined by ELISA
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8 days
|
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Assess the immunogenicity of inhaled TRL1068 as measured by anti-drug antibodies (ADAs)
時間枠:30 days
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Incidence of baseline and IP-emergent ADA (i.e., anti-TRL1068 antibodies) in serum will determined by electrochemiluminescence assay
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30 days
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- TRL1068-108
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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