Study to Evaluate Safety and Activity of TRL345 in Healthy Volunteers

NCT05408091 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: TRL345-102
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This study in healthy volunteers will provide a basis for evaluation of TRL345 as a first in human study, specifically, important safety, tolerability, and pharmacokinetic data, and provide serum samples for ex vivo studies of concentration-dependent antiviral activity to support the dose selection for as well as design and conduct of a clinical study in transplant patients.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (12)

• Incidence of abnormal physical exam findings

  Clinically-significant abnormal physical exam findings will be reviewed

  11 weeks

• Severity of abnormal physical exam findings

  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).

  11 weeks

• Incidence of abnormal serum chemistries and hematology

  Clinically-significant abnormal laboratory results findings will be reviewed

  11 weeks

• Severity of abnormal serum chemistries and hematology

  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).

  11 weeks

• Incidence of abnormal vital signs (temperature)

  Clinically-significant abnormal temperatures will be reviewed

  11 weeks

• Severity of abnormal vital signs (temperature)

  Clinically-significant abnormal temperatures will be reviewed

  11 weeks

• Incidence of abnormal vital signs (blood pressure)

  Clinically-significant abnormal blood pressures will be reviewed

  11 weeks

• Severity of abnormal vital signs (blood pressure)

  Clinically-significant abnormal blood pressures will be reviewed

  11 weeks

• Incidence of abnormal vital signs (heart rate)

  Clinically-significant abnormal heart rates will be reviewed

  11 weeks

• Severity of abnormal vital signs (heart rate)

  Clinically-significant abnormal heart rates will be reviewed

  11 weeks

• Incidence and Severity of Adverse Events

  reported AEs will be reviewed

  11 weeks

• Incidence of Serious Adverse Events

  reported SAEs will be reviewed

  11 weeks

Secondary Outcomes (6)

• Characterize the pharmacokinetics (PK) of a single IV infusion of TRL345 overall and by DG (Cmax)

  11 weeks

• Characterize the pharmacokinetics (PK) of a single IV infusion of TRL345 overall and by DG (Cmin)

  11 weeks

• Characterize the pharmacokinetics (PK) of a single IV infusion of TRL345 overall and by DG (CL)

  11 weeks

• Characterize the pharmacokinetics (PK) of a single IV infusion of TRL345 overall and by DG (Vss)

  11 weeks

• Characterize the pharmacokinetics (PK) of a single IV infusion of TRL345 overall and by DG (T1/2)

  11 weeks

Other Outcomes (9)

• The relationship of various concentrations of TRL345 in serum to antiviral activity against CMV will be determined

  11 weeks

• Explore if there are any differences in adverse events across dose groups

  11 weeks

• Explore if there are any differences in clinical labs across dose groups

  6 weeks

Study Arms (2)

Dose Level 1 - 1 mg/kg

EXPERIMENTAL

Randomized 6:2 (TRL345:placebo) via IV infusion

Drug: TRL345, a human monoclonal antibody

Dose Level 2 - 10 mg/kg

EXPERIMENTAL

Randomized 6:2 (TRL345:placebo) via IV infusion

Drug: TRL345, a human monoclonal antibody

Interventions

TRL345, a human monoclonal antibody DRUG

Anti-Human Cytomegalovirus (HCMV) IgG1κ Human Monoclonal Antibody

Dose Level 1 - 1 mg/kg; Dose Level 2 - 10 mg/kg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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 through Day 76. Men must also refrain from donating sperm from Day 1 through Day 76.

You may not qualify if:

• 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
• 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
• Diagnosis of diabetes mellitus
• History of acute or chronic pancreatitis or upper right quadrant postprandial discomfort or pain within the last 2 years
• Clinically relevant medical conditions that, in the opinion of the PI, may interfere with the evaluation of the trial drug, e.g., progressive cardiovascular disease
• Concurrent acute or chronic infections (e.g., viral infections, except chronic recurrent herpes simplex infections)
• Significant abnormal safety labs, defined as:

Sponsors & Collaborators

• Trellis Bioscience LLC: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

Related Publications (6)

• Kotton CN, Kumar D, Caliendo AM, Huprikar S, Chou S, Danziger-Isakov L, Humar A; The Transplantation Society International CMV Consensus Group. The Third International Consensus Guidelines on the Management of Cytomegalovirus in Solid-organ Transplantation. Transplantation. 2018 Jun;102(6):900-931. doi: 10.1097/TP.0000000000002191.

  PMID: 29596116 BACKGROUND

• Fowler KB, Stagno S, Pass RF, Britt WJ, Boll TJ, Alford CA. The outcome of congenital cytomegalovirus infection in relation to maternal antibody status. N Engl J Med. 1992 Mar 5;326(10):663-7. doi: 10.1056/NEJM199203053261003.

  PMID: 1310525 BACKGROUND

• Stagno S, Pass RF, Cloud G, Britt WJ, Henderson RE, Walton PD, Veren DA, Page F, Alford CA. Primary cytomegalovirus infection in pregnancy. Incidence, transmission to fetus, and clinical outcome. JAMA. 1986 Oct 10;256(14):1904-8.

  PMID: 3020264 BACKGROUND

• Turner KM, Lee HC, Boppana SB, Carlo WA, Randolph DA. Incidence and impact of CMV infection in very low birth weight infants. Pediatrics. 2014 Mar;133(3):e609-15. doi: 10.1542/peds.2013-2217. Epub 2014 Feb 2.

  PMID: 24488749 BACKGROUND

• Kalil AC, Freifeld AG, Lyden ER, Stoner JA. Valganciclovir for cytomegalovirus prevention in solid organ transplant patients: an evidence-based reassessment of safety and efficacy. PLoS One. 2009;4(5):e5512. doi: 10.1371/journal.pone.0005512. Epub 2009 May 13.

  PMID: 19436751 BACKGROUND

• Marty FM, Ljungman PT, Chemaly RF, Wan H, Teal VL, Butterton JR, Yeh WW, Leavitt RY, Badshah CS. Outcomes of patients with detectable CMV DNA at randomization in the phase III trial of letermovir for the prevention of CMV infection in allogeneic hematopoietic cell transplantation. Am J Transplant. 2020 Jun;20(6):1703-1711. doi: 10.1111/ajt.15764. Epub 2020 Jan 18.

  PMID: 31883426 BACKGROUND

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2022
• First Posted: June 7, 2022
• Study Start: September 14, 2023
• Primary Completion: December 23, 2024
• Study Completion: December 23, 2024
• Last Updated: April 10, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)