- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT07644195
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
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Anslået)
Fase
- Fase 1
Kontakter og lokationer
Studiekontakt
- Navn: Anton (Tony) Leighton, MD
- Telefonnummer: 650-838-1400
- E-mail: clinicalstudies@trellisbio.com
Undersøgelse Kontakt Backup
- Navn: Adriane Kisch-Hancock
- Telefonnummer: 650-838-1400
- E-mail: AKisch-Hancock@trellisbio.com
Studiesteder
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Nebraska
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Lincoln, Nebraska, Forenede Stater, 68502
- Celerion
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Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
- Voksen
- Ældre voksen
Tager imod sunde frivillige
Beskrivelse
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
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Sekventiel tildeling
- Maskning: Firedobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: Single Dose
Randomized 5:2 (TRL1068:placebo) via inhalation.
Administered once on Day 1.
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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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Eksperimentel: 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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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Incidence of abnormal physical exam findings
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 30 days
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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)
Tidsramme: 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
Tidsramme: 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
Tidsramme: 30 days
|
reported SAEs will be reviewed
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30 days
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Characterize the pharmacokinetics (PK) of inhaled TRL1068 overall and by DG (Cmax)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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 (Vss)
Tidsramme: 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)
Tidsramme: 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)
Tidsramme: 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
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Samarbejdspartnere og efterforskere
Sponsor
Samarbejdspartnere
Datoer for undersøgelser
Studer store datoer
Studiestart (Anslået)
Primær færdiggørelse (Anslået)
Studieafslutning (Anslået)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- TRL1068-108
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
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