Viropharma- Resistant CMV

Overview

Status: Completed
Keywords: CMV , Cytomegalovirus , Resist , Refractory , Infectious disease , Transplantation-Infectious disease , Transplant , immunosuppressed , Maribavir
IRB Number: 00066102
Specialty: Infectious Diseases, Transplant Surgery, Infectious Diseases
Sub Specialties: Viral infections, Solid and Bone Marrow Transplant

Brief Summary

The objectives of this study are (1) to assess the safety and tolerability 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, (2) to assess the antiviral activity of different doses of

maribavir in this subject population, (3) to evaluate the pharmacokinetics and

pharmacodynamics of maribavir in this subject population, and (4) to identify a dosing

regimen for treatment of CMV infection in future studies.

Principal Investigator: Fuad Shihab
Department: Nephrology
Co Investigator: Lonnie Smith
Co Investigator: Jeffrey Campsen
Co Investigator: Adrian Carlson
Co Investigator: Jo Abraham
Co Investigator: Nicole Kenyon
Co Investigator: Crystal Truax
Co Investigator: Faris Ahmed
Co Investigator: Edward Nelson

Contact Information

Name:Amber Lamph
Phone: 8015853845
Email: amber.lamph@hsc.utah.edu

Inclusion Criteria

Subjects must:

1. Be 12 years of age. (University of Utah will enroll age 18 and older only)

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 as determined by quantitative PCR or comparable

quantitative CMV assay type. Results from either the central laboratory or a

local laboratory can be used for qualification.

5. Have a current CMV infection that is resistant or refractory to treatment, defined

as follows:

Resistant:

Documentation of one or more CMV genetic mutations associated with

resistance to ganciclovir/valganciclovir and/or foscarnet (see Appendix VIII)

AND

Documented failure to achieve >1 log decrease in CMV DNA level in

blood/plasma after an interval of 2 or more weeks of treatment with IV

ganciclovir, oral valganciclovir, or IV foscarnet (or any combination thereof)

 

Refractory:

Documented failure to achieve >1 log decrease in CMV DNA level in

blood/plasma after an interval of 2 or more weeks of treatment with IV

ganciclovir, oral valganciclovir, or IV foscarnet (or any combination thereof).

 

6. If female, be either postmenopausal, surgically sterile, or have a negative β-

human chorionic gonadotropin (β-HCG) test prior to randomization (pregnancy

test results from either the central laboratory or a local laboratory can be used for

qualification). Women of child bearing potential also must agree to use an

acceptable method of birth control, as determined by the investigator, during the

study drug administration period and for 3 months afterward. Hormonal

contraceptives should not be used as the sole method of birth control.

If male, must agree to use an acceptable method of birth control, as determined

by the investigator, during the study drug administration period and for 3 months

afterward.

7. Be able to swallow tablets, or receive crushed tablets via a nasogastric or

orogastric tube.

8. If adult (age 18 years), be informed of the nature of the study and provide

written informed consent before any study-specific procedures are performed.

If child (age <18 years), have a parent/legal guardian who is willing and able to

provide written informed consent for the child to participate in the study (with

assent from the child when appropriate).

9- Be assessed by the investigator to determine whether prophylaxis for non-CMV herpes virus infections (e.g., herpes simplex virus [HSV type 1 and type 2] and varicella zoster [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

Exclusion Criteria

Subjects must not:

1. Be receiving any of the following therapies when study drug is initiated:

ganciclovir

valganciclovir

foscarnet

cidofovir *

CMV immune globulin (CMV-IGIV, Cytogam®) *

leflunomide *

artesunate

any investigational (unapproved) agent with known anti-CMV activity

NOTE: A subject may have received any of the above listed drugs prior to

enrollment. If this is the case, these drugs must be discontinued before the first

dose of study drug; drugs denoted with * must be discontinued at least 14 days

before commencement of dosing with study drug.

2. Have a current CMV infection that is considered resistant or refractory due to

inadequate adherence to prior oral anti-CMV treatment, to the best knowledge of

the investigator.

3. Have severe vomiting, diarrhea, or other severe gastrointestinal illness within

24 hours prior to the time of enrollment that would preclude administration of

oral/enteral medication.

4. Have severe hepatic impairment, defined as Child-Pugh Class C, based on

screening clinical and laboratory assessments (see Appendix XI).

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 (as determined by β-HCG testing prior to randomization) or

breastfeeding.

8. Have any clinically significant medical or surgical condition that in the

investigator’s or sponsor’s opinion could interfere with the administration of

study drug, interpretation of study results, or compromise the safety or wellbeing

of the subject.