Clinical trial NCT01611974: Maribavir for Treatment of Resistant or Refractory CMV Infections in Transplant Recipients
Official title: A Phase 2, Randomized Study to Assess the Safety and Anti-cytomegalovirus (CMV) Activity of Different Doses of Maribavir for Treatment of CMV Infections That Are Resistant or Refractory to Treatment With Ganciclovir/Valganciclovir or Foscarnet in Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cytomegalovirus (CMV)
Keywords: transplant
treatment
resistant
CMV
refractory
cytomegalovirus
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2012-06-05
Enrollment: 120
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will assess safety, antiviral activity, and pharmacokinetics of different doses of maribavir administered orally for up to 24 weeks for treatment of CMV infections that are resistant or refractory to treatment with ganciclovir/valganciclovir or foscarnet in recipients of stem cell or solid organ transplants.


Eligibility criteria: Inclusion Criteria

1. Be ≥12 years of age.
2. Weigh ≥ 40 kg.
3. Be a recipient of stem cell or solid organ transplantation.
4. Have documented CMV infection in blood or plasma, with a screening value of ≥1,000 DNA copies/mL.
5. Have a current CMV infection that is resistant (known CMV genetic mutations) or refractory (clinical failure to respond) to treatment with ganciclovir/valganciclovir and/or foscarnet.
6. If female, be either postmenopausal, surgically sterile, or have a negative pregnancy test prior to randomization.
7. Be able to swallow tablets.
8. If adult, provide written informed consent. If child (age \<18 years), have a parent/legal guardian who is willing and able to provide written informed consent (with assent from the child when appropriate).
9. Be assessed by the investigator to determine whether prophylaxis for non-CMV herpesvirus infections (e.g., herpes simplex virus \[HSV type 1 and type 2\] and varicella zoster virus \[VZV\]) is appropriate according to institutional guidelines or standard practices, keeping in mind that maribavir is not active in vitro against these viruses.

Exclusion Criteria

1. Be receiving any other anti-CMV agent(s).
2. Have a current CMV infection that is considered resistant or refractory due to inadequate adherence to prior oral anti-CMV treatment.
3. Have severe vomiting, diarrhea, or other severe gastrointestinal illness within 24 hours prior to the time of enrollment.
4. Have severe hepatic impairment.
5. Require mechanical ventilation or vasopressors for hemodynamic support at the time of enrollment.
6. Have expected survival less than 6 weeks.
7. Be pregnant or breastfeeding.
8. Other clinically significant medical or surgical condition.

Primary outcomes:
measure: Number of Participants With Confirmed Undetectable Plasma Cytomegalovirus (CMV) Within 6 Weeks
timeFrame: 6 weeks
measure: Number of Participants With a Treatment Emergent Adverse Event (TEAE).
timeFrame: 25 weeks
Secondary outcomes:
measure: Number of Participants With CMV Recurrence
timeFrame: 36 weeks
measure: Time to First Confirmed Undetectable Plasma CMV DNA Within 6 Weeks and at Any Time During The Study
timeFrame: 6 weeks after start of treatment, within 36 weeks of start of treatment
measure: Time to CMV Recurrence
timeFrame: 36 weeks
measure: Maximum Concentration (Cmax) of Maribavir
timeFrame: pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit
measure: Time to Maximum Concentration (Tmax) of Maribavir
timeFrame: pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit
measure: Time of Last Non-Zero Concentration (Tlast) of Maribavir
timeFrame: pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit
measure: Area Under The Plasma Concentration Versus Time Curve From The Time of Dosing to The Last Measurable Concentration (AUClast) of Maribavir
timeFrame: pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit
measure: Half-Life (T½) of Maribavir
timeFrame: pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Denver
country: United States
facility: University of Colorado
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Worcester
country: United States
facility: University of Massachusetts
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health Care System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburg
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt Medical Center
state: Tennessee
city: San Antonio
country: United States
facility: Methodist Healthcare System
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Chou S, Song K, Wu J, Bo T, Crumpacker C. Drug Resistance Mutations and Associated Phenotypes Detected in Clinical Trials of Maribavir for Treatment of Cytomegalovirus Infection. J Infect Dis. 2022 Sep 4;226(4):576-584. doi: 10.1093/infdis/jiaa462.
citation: Papanicolaou GA, Silveira FP, Langston AA, Pereira MR, Avery RK, Uknis M, Wijatyk A, Wu J, Boeckh M, Marty FM, Villano S. Maribavir for Refractory or Resistant Cytomegalovirus Infections in Hematopoietic-cell or Solid-organ Transplant Recipients: A Randomized, Dose-ranging, Double-blind, Phase 2 Study. Clin Infect Dis. 2019 Apr 8;68(8):1255-1264. doi: 10.1093/cid/ciy706.
citation: Schubert A, Ehlert K, Schuler-Luettmann S, Gentner E, Mertens T, Michel D. Fast selection of maribavir resistant cytomegalovirus in a bone marrow transplant recipient. BMC Infect Dis. 2013 Jul 19;13:330. doi: 10.1186/1471-2334-13-330.