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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.
Full description
Human cytomegalovirus (HCMV) is the most common medically significant infection in transplant patients. HCMV is usually a serious and even fatal infection in newborn SCID infants requiring hematopoietic stem cell transplant. HCMV is also the leading cause of congenital viral infection, with an incidence in the United States of 1-3% of live births. Primary HCMV infection during early pregnancy poses a 30-40% risk of intrauterine transmission. Approximately 10-15% of congenitally infected infants are symptomatic, presenting with intrauterine growth restriction and permanent birth defects, including neurological deficiencies, retinopathy, and sensori-neuronal deafness; of the infected but asymptomatic infants, 15-20% will later develop permanent sequelae. Trellis Bioscience is developing TRL345, a fully human monoclonal antibody that has specificity to the AD-2 site I in gB of HCMV, both for transplant patients and for the prevention of maternal HCMV infection during pregnancy.
Antibody therapy provides an alternative to antiviral drugs with an expectation of qualitatively lower toxicity. The leading small molecule antiviral effective against HCMV, ganciclovir (and its oral prodrug formulation valganciclovir), has side effects (including neutropenia, nephrotoxicity, and potential mutagenicity) that make its use problematic for major indications, including congenital transmission or the early post-transplant period for HCT. Although the recently approved small molecule antiviral letermovir has reduced neutropenic activity and is therefore useful in hematopoietic cell transplantation (HCT), it has not eliminated CMV reactivation in adult HCT patients.
Enrollment
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Inclusion criteria
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
ECG with clinically significant findings, including:
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:
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
Primary purpose
Allocation
Interventional model
Masking
16 participants in 2 patient groups
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Central trial contact
Anton (Tony) Leighton, MD; Adriane Kisch-Hancock
Data sourced from clinicaltrials.gov
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