Maribavir for Treatment of Resistant or Refractory CMV Infections in Transplant Recipients

NCT01611974 | Completed Phase 2 Results DMC

• 2 other identifiers: 1263-202SHP620-202
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 32

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.

Conditions

Cytomegalovirus (CMV)

Keywords

transplant; treatment; resistant; CMV; refractory; cytomegalovirus

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Confirmed Undetectable Plasma Cytomegalovirus (CMV) Within 6 Weeks

  Blood samples were collected at the study sites, processed to plasma aliquots, and sent to the central laboratory for quantitative CMV DNA polymerase chain reaction (PCR) testing. Plasma samples were assayed for CMV concentration using a qualified PCR method. This method was linear over 200-100,000 viral copies/mL with a lower limit of quantification (LLOQ) of 200 copies/mL. Results below LLOQ were considered undetectable. Confirmed undetectable plasma CMV DNA within 6 weeks was defined as 2 consecutive post-baseline, on-treatment undetectable results separated by \>/= 5 days (assessed by the central laboratory). Samples were collected on Days 1 and 8, weekly during Weeks 2-6, and once in Weeks 8, 10, 12, 16, 20, 24 (treatment) and Weeks 1, 4, 8, 12 (follow-up). Permissible assessment windows were: Days 8-15 +/- 1 day; Weeks 3-4 +/- 2 days; Weeks 5-6 +/- 3 days; Weeks 8-12 +/- 4 days; Weeks 16-24 +/- 7 days (treatment) and Weeks 1-4 +/- 2 days; Weeks 8-12 +/- 4 days (follow-up).

  6 weeks

• Number of Participants With a Treatment Emergent Adverse Event (TEAE).

  Treatment-emergent adverse events are those events that occurred on or after study drug administration through 7 days after the last dose of study drug, or are events that occurred prior to study drug administration and recurred with increased severity after taking study drug through 7 days after the last dose of study drug.

  25 weeks

Secondary Outcomes (8)

• Number of Participants With CMV Recurrence

  36 weeks

• Time to First Confirmed Undetectable Plasma CMV DNA Within 6 Weeks and at Any Time During The Study

  6 weeks after start of treatment, within 36 weeks of start of treatment

• Time to CMV Recurrence

  36 weeks

• Maximum Concentration (Cmax) of Maribavir

  pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit

• Time to Maximum Concentration (Tmax) of Maribavir

  pre-dose and 1, 2, 3, 4, 6, 8, and 12 hours post-dose on Day 8 and the Week 4 visit

Study Arms (3)

Maribavir 400 mg twice daily

EXPERIMENTAL

Drug: Maribavir

Maribavir 800 mg twice daily

EXPERIMENTAL

Drug: Maribavir

Maribavir 1200 mg twice daily

EXPERIMENTAL

Drug: Maribavir

Interventions

Maribavir DRUG

Tablet for oral administration

Maribavir 1200 mg twice daily; Maribavir 400 mg twice daily; Maribavir 800 mg twice daily

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Be ≥12 years of age.
• Weigh ≥ 40 kg.
• Be a recipient of stem cell or solid organ transplantation.
• Have documented CMV infection in blood or plasma, with a screening value of ≥1,000 DNA copies/mL.
• 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.
• If female, be either postmenopausal, surgically sterile, or have a negative pregnancy test prior to randomization.
• Be able to swallow tablets.
• 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).
• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Shire: lead

Study Sites (32)

UCLA Medical Center

Los Angeles, California, 90095, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

University of Colorado

Denver, Colorado, 80045, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Tampa General Hospital

Tampa, Florida, 33614, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University Medical Center

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Ochsner Clinic Foundation

New Orleans, Louisiana, 70121, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21205, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of Massachusetts

Worcester, Massachusetts, 01655, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Health Care System

Detroit, Michigan, 48202, United States

Location

University of Minnesota Medical Center

Minneapolis, Minnesota, 55454, United States

Location

University of Nebraska

Omaha, Nebraska, 68198, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 30322, United States

Location

Wake Forest Medical Center

Winston-Salem, North Carolina, 27157, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

University of Pittsburg

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Vanderbilt Medical Center

Nashville, Tennessee, 37212, United States

Location

Methodist Healthcare System

San Antonio, Texas, 78229, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

University of Washington

Seattle, Washington, 98109, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98195, United States

Location

Related Publications (5)

• Vernooij RW, Michael M, Ladhani M, Webster AC, Strippoli GF, Craig JC, Hodson EM. Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2024 May 3;5(5):CD003774. doi: 10.1002/14651858.CD003774.pub5.

  PMID: 38700045 DERIVED

• Sun K, Fournier M, Sundberg AK, Song IH. Maribavir: Mechanism of action, clinical, and translational science. Clin Transl Sci. 2024 Jan;17(1):e13696. doi: 10.1111/cts.13696.

  PMID: 38071422 DERIVED

• 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.

  PMID: 32726419 DERIVED

• 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.

  PMID: 30329038 DERIVED

• 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.

  PMID: 23870704 DERIVED

MeSH Terms

Interventions

maribavir

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2012
• First Posted: June 5, 2012
• Study Start: July 17, 2012
• Primary Completion: December 5, 2014
• Study Completion: December 5, 2014
• Last Updated: June 2, 2021
• Results First Posted: December 17, 2015

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

US (32)