Prevention of CMV Infection or Disease Clinical Trial
Official title:
A Phase III Randomized, Placebo-controlled Clinical Trial to Evaluate the Safety and Efficacy of MK-8228 (Letermovir) for the Prevention of Clinically Significant Human Cytomegalovirus (CMV) Infection in Adult, CMV-Seropositive Allogeneic Hematopoietic Stem Cell Transplant Recipients
| Verified date | August 2019 |
| Source | Merck Sharp & Dohme Corp. |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
The study evaluated the efficacy and safety of letermovir (MK-8228) for the prevention of clinically-significant CMV infection in adult, CMV-seropositive recipients of allogeneic hematopoietic stem cell transplant (HSCT). The hypothesis being tested was that MK-8228 is superior to placebo in the prevention of clinically-significant CMV infection through Week 24 post-transplant.
| Status | Completed |
| Enrollment | 570 |
| Est. completion date | November 21, 2016 |
| Est. primary completion date | August 8, 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Has documented seropositivity for CMV within 1 year before hematopoietic stem cell transplant (HSCT) - Receiving first allogeneic HSCT (bone marrow, peripheral blood stem cell, or cord blood transplant) - Female or male participant who is not of reproductive potential, or, if of reproductive potential, agrees to true abstinence or to use (or have their partner use) 2 acceptable methods of birth control from the time of consent through 90 days after the last dose of study drug - Able to read, understand, and complete questionnaires and diaries Exclusion Criteria: - Received a previous allogeneic HSCT (previous autologous HSCT is acceptable) - History of CMV end-organ disease within 6 months before randomization - Has evidence of CMV viremia (if tested) at any time from either signing of the Informed Consent Form or the HSCT procedure, whichever is earlier, until the time of randomization. - Received the following within 7 days before screening or plans to receive during the study: ganciclovir, valganciclovir, foscarnet, acyclovir, valacyclovir, or famciclovir - Received the following within 30 days before screening or plan to receive during the study: cidofovir, CMV hyper-immune globulin, any investigational CMV antiviral agent or biological therapy - Has suspected or known hypersensitivity to ingredients of MK-8228 (letermovir) formulations - Has severe hepatic insufficiency within 5 days before randomization - Has end-stage renal impairment - Has an uncontrolled infection on the day of randomization - Requires mechanical ventilation or is hemodynamically unstable at the time of randomization - Has documented positive results for human immunodeficiency virus (HIV) antibody, hepatitis C virus (HCV) antibody with detectable HCV ribonucleic acid, or hepatitis B surface antigen (HBsAg) within 90 days before randomization - Has active solid tumor malignancies with the exception of localized basal cell or squamous cell skin cancer or the condition under treatment (for example, lymphoma) - Is pregnant or expecting to conceive, is breastfeeding, or plans to breastfeed from the time of consent through 90 days after the last dose of study drug - Is expecting to donate eggs or sperm from the time of consent through 90 days after the last dose of study drug - Has participated in a study with an unapproved investigational compound (monoclonal antibodies are excepted) or device within 28 days of the first dose of study drug - Has previously participated in a MK-8228 (letermovir) study - Has, is, or is planning (during the study) to participate in any study involving administration of a CMV vaccine or another CMV investigational agent - Is a user of recreational or illicit drugs or has a recent history (<=1 year) of drug or alcohol abuse or dependence |
| Country | Name | City | State |
|---|---|---|---|
| n/a | |||
| Lead Sponsor | Collaborator |
|---|---|
| Merck Sharp & Dohme Corp. |
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Percentage of Participants With One or More Adverse Events up to Week 48 Post-transplant | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. | Up to Week 48 post-transplant | |
| Other | Percentage of Participants Discontinued From Study Medication Due to an Adverse Event | An adverse event is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An adverse event can therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an adverse event. | Up to Week 14 post-transplant | |
| Primary | Percentage of Participants With Clinically-significant CMV Infection up to Week 24 Post-transplant | Clinically-significant CMV infection was defined as either one of the following: 1) onset of CMV end-organ disease, or 2) initiation of anti-CMV pre-emptive therapy based on documented CMV viremia and the clinical condition of the participant. The percentage of participants with clinically-significant CMV infection was assessed. | Up to Week 24 post-transplant | |
| Secondary | Time to Onset of Clinically-significant CMV Infection (Kaplan-Meier Estimate of Percentage of Participants With a Qualifying Event at Week 24 Post-transplant) | Clinically-significant CMV infection was defined as either one of the following: 1) onset of CMV end-organ disease, or 2) initiation of anti-CMV pre-emptive therapy based on documented CMV viremia and the clinical condition of the participant. Time to onset of clinically-significant CMV infection was defined from the day of transplantation to the day the participant developed clinically-significant CMV infection, and was analyzed by the Kaplan-Meier method. Participants were censored at the last assessment for participants who discontinued or did not develop clinically-significant CMV infection. | Up to Week 24 post-transplant | |
| Secondary | Percentage of Participants With Clinically-significant CMV Infection up to Week 14 Post-transplant | Clinically-significant CMV infection was defined as either one of the following: 1) onset of CMV end-organ disease, or 2) initiation of anti-CMV pre-emptive therapy based on documented CMV viremia and the clinical condition of the participant. The percentage of participants with clinically-significant CMV infection was assessed. | Up to Week 14 post-transplant | |
| Secondary | Percentage of Participants With CMV End-organ Disease up to Week 24 Post-transplant | CMV end-organ disease met per-protocol diagnostic criteria for CMV-pneumonia, gastrointestinal disease, hepatitis, central nervous system disease, retinitis, nephritis, cystitis, myocarditis, pancreatitis, or other disease categories. Only Clinical Adjudication Committee-confirmed CMV end-organ disease was included in this analysis. The percentage of participants with CMV end-organ disease was assessed. | Up to Week 24 post-transplant | |
| Secondary | Percentage of Participants With CMV End-organ Disease up to Week 14 Post-transplant | CMV end-organ disease met per-protocol diagnostic criteria for CMV-pneumonia, gastrointestinal disease, hepatitis, central nervous system disease, retinitis, nephritis, cystitis, myocarditis, pancreatitis, or other disease categories. Only Clinical Adjudication Committee-confirmed CMV end-organ disease was included in this analysis. The percentage of participants with CMV end-organ disease was assessed. | Up to Week 14 post-transplant | |
| Secondary | Percentage of Participants With Pre-emptive Therapy for CMV Viremia up to Week 14 Post-transplant | Initiation of anti-CMV pre-emptive therapy was based on documented CMV viremia and the clinical condition of the participant. The percentage of participants with initiation of anti-CMV pre-emptive anti-CMV therapy was assessed. | Up to Week 14 post-transplant | |
| Secondary | Percentage of Participants With Pre-emptive Therapy for CMV Viremia up to Week 24 Post-transplant | Initiation of anti-CMV pre-emptive therapy was based on documented CMV viremia and the clinical condition of the participant. The percentage of participants with initiation of anti-CMV pre-emptive anti-CMV therapy was assessed. | Up to Week 24 post-transplant | |
| Secondary | Time to Initiation of Pre-emptive Therapy for CMV Viremia (Kaplan-Meier Estimate of Percentage of Participants With a Qualifying Event at Week 24 Post-transplant) | The need for anti-CMV pre-emptive therapy was based on documented CMV viremia and the clinical condition of the participant. The outcome was calculated from the day of transplantation to the start of anti-CMV pre-emptive therapy, and was analyzed by the Kaplan-Meier method. Participants were censored at the last assessment for participants who discontinued or did not initiate pre-emptive therapy. | Up to Week 24 post-transplant |