Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Letermovir Treatment for Refractory or Resistant Cytomegalovirus Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03728426
Recruitment Status : Recruiting
First Posted : November 2, 2018
Last Update Posted : January 28, 2019
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Francisco M. Marty, MD, Dana-Farber Cancer Institute

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Cytomegalovirus Infections Drug: Letermovir Phase 2

Detailed Description:

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Letermovir Treatment for Patients Experiencing Refractory or Resistant Cytomegalovirus Infection or Disease With Concurrent Organ Dysfunction
Actual Study Start Date : January 11, 2019
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Letermovir

Arm Intervention/treatment
Experimental: Letermovir
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.

Other Name: Prevymis




Primary Outcome Measures :
  1. Virological response on treatment Week 6 [ Time Frame: 6 weeks ]

    A ≥2 log decrease in plasma CMV DNA from baseline, or an undetectable CMV DNA, measured on treatment week 6.

    For patients with CMV disease, 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.])



Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 6 months ]
    number of patients alive

  2. CMV progression-free survival [ Time Frame: 6 months ]
    Time from study enrollment to CMV progression or death whichever occurs first

  3. Kinetics of viral clearance and potential emergence of letermovir-resistant CMV virus in patients treated in this setting [ Time Frame: 6 months ]
    time to undetectable plasma CMV DN and time to breakthrough infection in patients receiving letermovir treatment who experience an initial virological response.

  4. Proportion of patients with a clinically meaningful treatment response to letermovir treatment [ Time Frame: 6 Weeks ]
    Virological response and a concomitant clinical response in patients with CMV disease by Week 6 of treatment.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥12 years
  • Weight ≥30 kg
  • Transplant recipient (HCT, SOT) or other immunocompromised patients including those with HIV infection that require antiviral treatment for CMV.
  • Documented CMV disease or persistent CMV infection (CMV virus load above 500 IU/mL on consecutive measurements, at least one day apart).
  • CMV infection is refractory to treatment (defined as ≥14 days of standard CMV treatment without clinical improvement for CMV disease, or failure to achieve >1 log reduction in CMV VL after ≥14 days of standard treatment for CMV infection)16,17
  • Current CMV infection has documented genotypic resistance to ganciclovir or foscarnet.
  • For patients with any prior CMV infection episode that broke through letermovir prophylaxis, but not during the current CMV infection, documentation of letermovir susceptibility testing should demonstrate absence of letermovir mutations known to confer resistance to letermovir.
  • 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.

  • Combinations of genotypic antiviral resistance and organ dysfunction that lead to eligibility are presented in the full protocol eligibility table.
  • 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.

  • Able to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to letermovir.
  • Known history of cirrhosis with Child-Pugh Class C hepatic insufficiency at screening.
  • Acute liver injury at baseline meeting Hy's law.
  • Current CMV infection broke through letermovir prophylaxis.
  • Patients with life expectancy of less than a week. Determination of life expectancy will be discussed with the patient's primary treatment physician.
  • Patient taking strong inhibitors or inducers of hepatic CYP enzymes including rifampicin, phenytoin, clarithromycin, ritonavir, or cobicistat.
  • HIV patients who are receiving antiretroviral treatment protease inhibitors (darunavir, lopinavir, etc) whether by themselves or boosted with ritonavir or cobicistat, or HIV patients receiving cyclosporine treatment due to strong drug-drug interactions.
  • Combinations of genotypic antiviral resistance and organ dysfunction that do not meet eligibility criteria are described in the full protocol eligibility table.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03728426


Contacts
Layout table for location contacts
Contact: Francisco M Marty, MD 617-525-8418 fmarty@bwh.harvard.edu

Locations
Layout table for location information
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Francisco M Marty, MD       fmarty@bwh.harvard.edu   
Principal Investigator: Francisco M Marty, MD         
Massachusetts General Hospital Cancer Center Recruiting
Boston, Massachusetts, United States, 02214
Contact: Alyssa R Letourneau, MD       aletourneau@partners.org   
Principal Investigator: Alyssa R Letourneau, MD         
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02215
Contact: Sandra Burchett, MD       sandra.burchett@childrens.harvard.edu   
Principal Investigator: Sandra Burchett, MD         
Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Francisco M Marty, MD       fmarty@bwh.harvard.edu   
Principal Investigator: Francisco M Marty, MD         
Sponsors and Collaborators
Dana-Farber Cancer Institute
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Principal Investigator: Francisco Marty, MD Dana-Farber Cancer Institute

Layout table for additonal information
Responsible Party: Francisco M. Marty, MD, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT03728426     History of Changes
Other Study ID Numbers: 18-348
First Posted: November 2, 2018    Key Record Dates
Last Update Posted: January 28, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Francisco M. Marty, MD, Dana-Farber Cancer Institute:
Cytomegalovirus Infections
CMV

Additional relevant MeSH terms:
Layout table for MeSH terms
Infection
Communicable Diseases
Cytomegalovirus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases