Phase 3
Completed N=352
Efficacy and Safety Study of Maribavir Treatment Compared to Investigator-assigned Treatment in Transplant Recipients With Cytomegalovirus (CMV) Infections That Are Refractory or Resistant to Treatment With Ganciclovir, Valganciclovir, Foscarnet, or Cidofovir
Cytomegalovirus (CMV)
Source: ClinicalTrials.gov NCT02931539 ↗
Enrolled (actual)
352
Serious AEs
55.9%
Results posted
Sep 2021
Primary outcomePrimary: Percentage of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) (CMV Viremia Clearance) at End of Week 8 — 23.9; 55.7 percentage of participants — p=<0.001
◆ Published Evidence
Established
76citations · ~38 / year
Drug Resistance Assessed in a Phase 3 Clinical Trial of Maribavir Therapy for Refractory or Resistant Cytomegalovirus Infection in Transplant Recipients.
Summary
The purpose of this study is to compare the efficacy of maribavir to investigator-assigned anti-Cytomegalovirus (CMV) therapy in CMV viremia clearance in transplant recipients who are refractory or resistant to prior anti-CMV treatment.
Linked Publications (5)
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Drug Resistance Assessed in a Phase 3 Clinical Trial of Maribavir Therapy for Refractory or Resistant Cytomegalovirus Infection in Transplant Recipients.
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Maribavir: Mechanism of action, clinical, and translational science.
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Maribavir for refractory cytomegalovirus infection (with or without resistance) in solid organ transplant recipients: Subgroup analysis of the phase 3 randomized SOLSTICE study.
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Real-world effectiveness and tolerability of post solid organ transplant patients with CMV switching from valganciclovir treatment to maribavir: analysis using lab-linked claims data in the United States.
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Association Between Cytomegalovirus Viremia Clearance and Post-Solid Organ Transplant Mortality in Patients With Refractory Cytomegalovirus Infection: SOLSTICE Post Hoc Analysis.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Who Achieved Confirmed Clearance of Plasma Cytomegalovirus (CMV) Deoxyribonucleic Acid (DNA) (CMV Viremia Clearance) at End of Week 8 |
23.9; 55.7 | <0.001 sig |
| SECONDARY Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at End of Week 8, Followed by Maintenance of Treatment Effect at Week 16 |
10.3; 18.7 | 0.013 sig |
| SECONDARY Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance After Receiving 8 Weeks of Study-assigned Treatment |
18.8; 54.9; 5.1; 22.6; 5.1; 18.7 | — |
| SECONDARY Percentage of Participants Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control After Receiving 8 Weeks of Study-assigned Treatment Through Weeks 12, 16 and 20 |
18.8; 54.9; 5.1; 22.6; 5.1; 18.7 | — |
| SECONDARY Percentage of Participants Who Maintained CMV Viremia Clearance and CMV Infection Symptom Control at the End of Study Week 8 Through Weeks 12 and 20 Regardless of Whether Either Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy |
23.9; 55.7; 10.3; 22.6; 9.4; 18.3 | — |
| SECONDARY Percentage of Participants With Recurrence of CMV Viremia During the First 8 Weeks of Study Regardless of Whether Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy |
12.3; 17.9 | — |
| SECONDARY Percentage of Participants With Recurrence of CMV Viremia During the 12 Weeks Follow-up Period Regardless of Whether Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy |
21.5; 38.6 | — |
| SECONDARY Percentage of Participants With Recurrence of CMV Viremia at Any Time on Study Regardless of Whether Study-assigned Treatment Was Discontinued Before 8 Weeks of Therapy |
33.8; 56.5 | — |
| SECONDARY Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the First 8 Weeks of the Treatment |
9.7; 15.2 | — |
| SECONDARY Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the 12 Weeks of Follow-up Period |
35.5; 40.9 | — |
| SECONDARY Percentage of Participants Who Completed 8 Weeks of Study-assigned Treatment With Recurrence of CMV Viremia During the 20 Weeks of Study |
45.2; 56.1 | — |
| SECONDARY Percentage of Participants With Recurrence of CMV Viremia While on Study-assigned Treatment |
4.6; 15.8 | — |
| SECONDARY Percentage of Participants With Recurrence of CMV Viremia While Off Study-assigned Treatment During Follow-up Period |
29.2; 40.8 | — |
| SECONDARY Number of Participants Who Had Maribavir CMV Resistance at Baseline |
3; 1; 0; 0; 0; 1 | — |
| SECONDARY Number of Participants Who Had Post-baseline Resistance to Maribavir |
0; 4; 45; 0; 0; 0 | — |
| SECONDARY Number of Participants With All-cause Mortality by the End of the Study |
13; 27 | — |
| SECONDARY Time to All Cause Mortality |
73.0; 55.0 | 0.647 |
| SECONDARY Percentage of Participants Who Achieved Confirmed Clearance of Plasma CMV DNA (CMV Viremia Clearance) at End of Week 8 After Starting Maribavir Rescue Treatment |
50.0 | — |
| SECONDARY Percentage of Participants Receiving Maribavir Rescue Treatment Who Achieved Confirmed CMV Viremia Clearance and CMV Infection Symptom Control at Week 8 With Maintenance of Effect Through Week 16 |
27.3 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs During the On-treatment Observation Period |
106; 22; 228; 43; 11; 90 | — |
| SECONDARY Predose Concentration (Cmin) of Maribavir |
8.77; 8.57; 7.59; 5.75; 7.19; 5.65 | — |
| SECONDARY Area Under the Concentration Time Curve Over the 12-hour Dosing Interval at Steady State (AUC0-tau) of Marivabir for Adolescent Participants |
— | — |
| SECONDARY Maximum Plasma Concentration (Cmax) of Maribavir for Adolescent Participants |
— | — |
| SECONDARY Time When Maximum Concentration is Observed (Tmax) of Maribavir for Adolescent Participants |
— | — |
| SECONDARY Apparent Oral Clearance (CL/F) of Maribavir for Adolescent Participants |
— | — |
| SECONDARY Apparent Volume of Distribution (Vz/F) of Maribavir for Adolescent Participants |
— | — |
Eligibility Criteria
Inclusion Criteria
- The participant must be able to provide written, personally signed, and dated informed consent to participate in the study before completing any study-related procedures. As applicable, a parent/both parents or legally authorized representative (LAR) must provide signature of informed consent and there must be documentation of assent by the participant before completing any study-related procedures.
- The participant must be a recipient of hematopoietic stem cell or solid organ transplant.
- The participant must have a documented CMV infection in whole blood or plasma, with a screening value of greater than or equal to (>=) 2730 international units per milliliter (IU/mL) in whole blood or >= 910 IU/mL in plasma in 2 consecutive assessments, separated by at least 1 day, as determined by local or central specialty laboratory quantitative polymerase chain reaction (qPCR) or comparable quantitative CMV DNA results. Both samples should be taken within 14 days prior to randomization with second sample obtained within 5 days prior to randomization. The same laboratory and same sample type (whole blood or plasma) must be used for these assessments.
- The participant must have a current CMV infection that is refractory to the most recently administered of the four anti-CMV treatment agents. Refractory is defined as documented failure to achieve greater than (>) 1 log10 (common logarithm to base 10) decrease in CMV DNA level in whole blood or plasma after a 14 day or longer treatment period with intravenous (IV) ganciclovir/oral valganciclovir, IV foscarnet, or IV cidofovir.
a. Participants with documentation of 1 or more CMV genetic mutations associated with resistance to ganciclovir/valganciclovir, foscarnet, and/or cidofovir must also meet the definition of refractory CMV infection.
- The Investigator must be willing to treat the participant with at least one of the available anti-CMV drugs (ganciclovir, valganciclovir, foscarnet, or cidofovir). Note: Combination therapy with foscarnet and cidofovir is not permitted in the investigator-assigned anti-CMV treatment (IAT) arm due to the potential for serious nephrotoxicity.
- The participant must be >= 12 years of age at the time of consent.
- The participant must weigh >= 35 kilogram (kg).
- The participant must have all of the following results as part of screening laboratory assessments (results from either the central laboratory or a local laboratory can be used for qualification):
- Absolute neutrophil count (ANC) >= 1000/ millimeter cube (mm^3) (1.0 x 10^9/liter [L])
- Platelet count >= 25, 000/mm^3 [25 x 10^9/L],
- Hemoglobin >= 8 grams per deciliter (g/dL).
- Estimated glomerular filtration rate (eGFR) > 30 (milliliters per minute (mL/min) /1.73 square meter (m^2) as assessed by Modification of Diet in Renal Disease (MDRD) formula for participants >= 18 years of age or Schwartz formula for participants less than ( = 8 weeks.
Exclusion Criteria
- Have a current CMV infection that is considered refractory or resistant due to inadequate adherence to prior anti-CMV treatment, to the best knowledge of the Investigator.
- Require ganciclovir, valganciclovir, foscarnet, or cidofovir administration for conditions other than CMV when study treatment is initiated (example: herpes simplex virus (HSV) coinfection requiring use of any of these agents after the randomization) or would need a coadministration with maribavir for CMV infection. NOTE: A participant who is not continuing with the same anti-CMV drug(s) (ganciclovir, valganciclovir or foscarnet) for the study treatment (if randomized to the investigator assigned anti-CMV treatment arm), must discontinue their use before the first dose of study drug. If participant is currently being treated with cidofovir and is assigned another anti-CMV therapy by the investigator, the participant must discontinue its use at least 14 days prior to randomization at Visit 2/Day 0 and the first dose of study tr
Data sourced from ClinicalTrials.gov (NCT02931539) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.