A Phase 2 interventional study of Letermovir in Cytomegalovirus Infections, sponsored by Amy C. Sherman, MD. Completed at 4 sites in United States. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2023-03-08.
Sponsored by Amy C. Sherman, MD · Phase 2, Interventional, and Treatment
The trial will evaluate the safety and efficacy of letermovir antiviral treatment of active cytomegalovirus infection or cytomegalovirus disease in patients with infections that are refractory or resistant to available treatments or who are experiencing organ dysfunction that makes unsafe the use of available antiviral treatments.
This is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The FDA (the U.S. Food and Drug Administration) has not approved letermovir for treatment of cytomegalovirus infection, but it has approved letermovir for the prevention of cytomegalovirus infection in bone-marrow transplantation patients.
This is the first time that letermovir will be administered to children in a clinical trial.
Cytomegalovirus (CMV) is a common virus, which a majority of people acquire at some time in their life. CMV remains in your body, but does not cause symptoms in the majority of people. Patients with a weakened immune system (a system that protects you from infections) may be more at risk for the virus becoming active and causing damage to some of your organs, especially in the gut and lungs. If the virus becomes present above a certain quantity, the doctor usually prescribes a drug to treat the infection at this stage to avoid damage to the organs.
In this case, the virus is no longer responding to the prescribed drug, and other drug options will be harmful to the participant's health. Participants are being invited to take part in a research study for an investigational drug called letermovir. The purpose of this study is to find out whether letermovir is as effective and as safe in treating CMV infection in patients who cannot tolerate standard treatments such as ganciclovir or foscarnet.
6,687 studies on the registry are indexed under Infections; 807 are open to participants now.
This study's enrollment of 10 is below the median of 120 across 4,200 interventional studies indexed under Infections.
Browse Infections studies →This is the only study on the registry with Amy C. Sherman, MD as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Severe myelosuppression (ANC \<1000/µL, Hemoglobin \<8g/dL, or Platelets \<25,000/µL)17 or renal dysfunction (estimated creatinine clearance \<60 mL/min by MDRD in adults or \< 60 ml/min/1.73 m2 by bedside Schwartz equation in \< 18 years-old) at baseline or which develops during antiviral treatment.
--Patients who develop severe myelosuppression or renal dysfunction during antiviral treatment as defined above are eligible without having to meet the refractoriness/antiviral resistance criterion.
The effects of letermovir on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and 3 months after completion of letermovir administration. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of letermovir administration.
--Patients of childbearing potential must have a negative serum or urine pregnancy test.
Exclusion Criteria:
Open label letermovir will be administered daily for up to 12 weeks. The study allows an optional additional 12 weeks of treatment for secondary prophylaxis if clinically indicated.
Drug: Letermovir
Patients will receive intravenous or oral letermovir at a dose of 480mg/day. Patients weighing 40 or more kilograms will receive a second, loading, dose 12 hours after the first dose of letermovir treatment. For patients receiving concomitant cyclosporine treatment, the letermovir dose will be 240mg/day.
Also known as: Prevymis
Virological Response on Treatment Week 6
The virologic response milestones are defined as: 1) Any decrease in CMV DNA from baseline (Week 0), measured on week 3 and 2) A ≥2 log decrease in CMV DNA from baseline, or an undetectable CMV DNA, measured on week 6. For patients with clinical CMV disease, the clinical response milestones are defined as: 1) Stabilization of clinical disease by week 3 (i.e. no worsening signs or symptoms compared to week 1) as assessed by the site investigator and 2) Improvement or resolution of clinical disease by week 6 (i.e., improvement in signs and symptoms of affected organs \[resolution of diarrhea, pneumonia, hepatitis, retinitis, etc.\]) 3) Patients with clinical CMV disease should also meet virological response milestones outlined above to support the continuation of letermovir therapy. Patients who enter the study based solely on documented CMV disease by histopathology in the absence of quantifiable CMV virus load should remain nonquantifiable (less than 137 IU/mL).
Time frame: 6 weeks
Overall Survival
number of patients alive
Time frame: 6 months
CMV Progression-free Survival
Time from study enrollment to CMV progression or death whichever occurs first
Time frame: 6 months
Kinetics of Viral Clearance
time to undetectable plasma CMV DNA
Time frame: 6 months
Percent of Patients With a Clinically Meaningful Treatment Response to Letermovir Treatment
Virological response and a concomitant clinical response in patients with CMV disease by Week 6 of treatment. For patients with clinical CMV disease, the clinical response milestones are defined as: 1. Stabilization of clinical disease by week 3 (i.e. no worsening signs or symptoms compared to week 1) as assessed by the site investigator and 2. Improvement or resolution of clinical disease by week 6 (i.e., improvement in signs and symptoms of affected organs \[resolution of diarrhea, pneumonia, hepatitis, retinitis, etc.\]) 3. Patients with clinical CMV disease should also meet virological response milestones outlined above to support the continuation of letermovir therapy. Patients who enter the study based solely on documented CMV disease by histopathology in the absence of quantifiable CMV virus load should remain nonquantifiable (less than 137 IU/mL).
Time frame: 6 Weeks
Emergence of Letermovir-resistant CMV Virus in Patients Treated in This Setting
Number of participants with breakthrough letermovir-resistant CMV infection in patients receiving letermovir treatment who experienced an initial virological response.
Time frame: 6 months
163 individuals were screened, 10 were enrolled in the study from Dana-Farber Cancer Institute inpatient and outpatient settings.
| Milestone | Letermovir |
|---|---|
| Started | 10 |
| Completed | 7 |
| Not completed | 3 |
| Withdrew: Death | 3 |
The virologic response milestones are defined as: 1) Any decrease in CMV DNA from baseline (Week 0), measured on week 3 and 2) A ≥2 log decrease in CMV DNA from baseline, or an undetectable CMV DNA, measured on week 6. For patients with clinical CMV disease, the clinical response milestones are defined as: 1) Stabilization of clinical disease by week 3 (i.e. no worsening signs or symptoms compared to week 1) as assessed by the site investigator and 2) Improvement or resolution of clinical disease by week 6 (i.e., improvement in signs and symptoms of affected organs \[resolution of diarrhea, pneumonia, hepatitis, retinitis, etc.\]) 3) Patients with clinical CMV disease should also meet virological response milestones outlined above to support the continuation of letermovir therapy. Patients who enter the study based solely on documented CMV disease by histopathology in the absence of quantifiable CMV virus load should remain nonquantifiable (less than 137 IU/mL).
| Participants | Letermovir |
|---|---|
| Virological Response on Treatment Week 6 | 5 |
number of patients alive
| Participants | Letermovir |
|---|---|
| Overall Survival | 7 |
Time from study enrollment to CMV progression or death whichever occurs first
| days | Letermovir |
|---|---|
| CMV Progression-free Survival | 13 (13 to 19) |
time to undetectable plasma CMV DNA
| days | Letermovir |
|---|---|
| Kinetics of Viral Clearance | 166 (147 to 168) |
Virological response and a concomitant clinical response in patients with CMV disease by Week 6 of treatment. For patients with clinical CMV disease, the clinical response milestones are defined as: 1. Stabilization of clinical disease by week 3 (i.e. no worsening signs or symptoms compared to week 1) as assessed by the site investigator and 2. Improvement or resolution of clinical disease by week 6 (i.e., improvement in signs and symptoms of affected organs \[resolution of diarrhea, pneumonia, hepatitis, retinitis, etc.\]) 3. Patients with clinical CMV disease should also meet virological response milestones outlined above to support the continuation of letermovir therapy. Patients who enter the study based solely on documented CMV disease by histopathology in the absence of quantifiable CMV virus load should remain nonquantifiable (less than 137 IU/mL).
| Participants | Letermovir |
|---|---|
| Percent of Patients With a Clinically Meaningful Treatment Response to Letermovir Treatment | 0 |
Number of participants with breakthrough letermovir-resistant CMV infection in patients receiving letermovir treatment who experienced an initial virological response.
| Participants | Letermovir |
|---|---|
| Emergence of Letermovir-resistant CMV Virus in Patients Treated in This Setting | 0 |
Collected over 6 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Letermovir | 3/10 (30%) | 6/10 (60%) | 10/10 (100%) |
| Event | Letermovir |
|---|---|
| Lung InfectionInfections and infestations | 2/10 |
| DiarrheaGastrointestinal disorders | 1/10 |
| Heart FailureCardiac disorders | 1/10 |
| Immune system disorders - Other, specifyImmune system disorders | 1/10 |
| Cardiac ArrestCardiac disorders | 1/10 |
| Pulmonary edemaRespiratory, thoracic and mediastinal disorders | 1/10 |
| EncephalopathyNervous system disorders | 1/10 |
| Event | Letermovir |
|---|---|
| NauseaGastrointestinal disorders | 4/10 |
| DiarrheaGastrointestinal disorders | 2/10 |
| Alanine aminotransferase increasedHepatobiliary disorders | 2/10 |
| BacteremiaInfections and infestations | 2/10 |
| EpistaxisBlood and lymphatic system disorders | 2/10 |
| Peripheral sensory neuropathyNervous system disorders | 2/10 |
| PneumothoraxRespiratory, thoracic and mediastinal disorders | 2/10 |
| Rash maculo-papularSkin and subcutaneous tissue disorders | 2/10 |
| Upper respiratory infectionRespiratory, thoracic and mediastinal disorders | 2/10 |
| Vascular disordersVascular disorders | 2/10 |
| Age, Continuous(years) | Letermovir |
|---|---|
| Median | 62.15 (56.32 to 69.87) |
| Sex: Female, Male(Participants) | Letermovir |
|---|---|
| Female | 5 |
| Male | 5 |
| Ethnicity (NIH/OMB)(Participants) | Letermovir |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 9 |
| Unknown or Not Reported | 1 |
| Race (NIH/OMB)(Participants) | Letermovir |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 2 |
| White | 6 |
| More than one race | 0 |
| Unknown or Not Reported | 1 |
| Region of Enrollment(participants) | Letermovir |
|---|---|
| United States | 10 |
| Baseline CMV viral load(IU/mL) | Letermovir |
|---|---|
| Median | 1272 (925 to 2546) |
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