CMX001-301: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Phase 3 Study of the Safety, Tolerability, and Efficacy of CMX001 for the Prevention of Cytomegalovirus (CMV) Infection in CMV-seropositive (R+) Hematopoietic Stem Cell Transplant Recipients
- UT Southwestern Ambulatory Services
This is a randomized, double-blind, placebo-controlled, parallel group, multicenter study of CMX001 in CMV-seropositive subjects who have undergone allogeneic HSCT. The study will comprise a screening evaluation, a treatment phase of 10 to 14 weeks' duration (through Week 14), followed by a 10-week posttreatment phase (to Week 24), which are described as follows:
Screening: Potential subjects may be consented for participation in the study before or after transplant. Subjects providing written informed consent will be screened following transplant as soon as the subject can ingest tablets. as part of the screening procedures, CMV viremia (i.e., the measurement of
CMV deoxyribonucleic acid [Dna] in plasma by polymerase chain reaction [PCR] assay) must be assessed by the designated central virology laboratory within 5 days prior to randomization and only those subjects who are determined to be CMV viremia negative at screening (i.e., CMV Dna in plasma
is [Quote]not Detected[Quote] for the Roche CoBaS[RegisteredTM] ampliPrep/CoBaS[RegisteredTM] TaqMan[RegisteredTM] CMV Test used bybelow the lower limit of detection [LLoD [?] 100 copies/mL] for the PCR assay performed at the central virology laboratory) will be eligible for randomization. in addition, the results of any CMV viremia testing
(including CMV PCR, pp65 antigenemia, etc.) performed as part of, and at all prior assessments performed since transplant under local standard of care (SoC) since the qualifying transplant must also be negative, will be eligible for randomization. Subjects who were CMV viremia negative at screening,
but who are subsequently found to have been CMV viremic at baseline (i.e., at the predose assessment on the first dose day [FDD]) will be continued in the study.
Randomization: Subjects who meet all applicable eligibility criteria will be randomized to one
of the following two treatment arms in a 2:1 ratio using an automated integrated voice/web
response system (iV/WRS):
[?] Treatment 1: 100 mg CMX001 BiW
[?] Treatment 2: placebo BiW
Primary efficacy endpoint:
The primary efficacy endpoint of this study will be the incidence of clinically significant CMV infection through Week 24. For the purposes of this study, [Quote]clinically significant CMV infection[Quote] is defined as the occurrence of either of the following outcomes:
[?] onset of CMV end-organ disease, or
[?] initiation of anti-CMV specific PrT based on documented CMV viremia (as measured by the central virology laboratory) and the clinical condition of the subject as described in Section 6.3.5 of the protocol.
it is expected that approximately 450 subjects will be enrolled in this study at various hospitals across the united States and Canada. To be eligible to participate in the study, men and women have to meet the following minimum criteria:
[?] have undergone HCT,
[?] have evidence of previous CMV infection (called being [Quote]seropositive[Quote] for CMV), but have had no measurable virus in their blood since transplant,
[?] and at least 18 years of age or older
it is estimated that approximately 6 subjects will be enrolled at uT Southwestern.
(1) Allogeneic HSCT recipient who has prior evidence of CMV exposure before transplantation and who is CMV viremia negative at screening and at any other assessments performed prior to the FDD.
[Note: CMV viremia must be confirmed as negative (i.e., below the lower limit of detection [LLOD = 100 copies/mL] for the PCR assay performed by the central virology laboratory no more than 5 days prior to randomization. In addition, all CMV viremia results performed as part of local SoC since the qualifying transplant must also be negative.]
(2) Aged >= 18 years.
[Note: The minimum acceptable age may be higher depending on local regulations.]
(3) If male, willing to use an acceptable contraceptive method(s) throughout the duration of his participation in the study, i.e., through Week 24.
(4) If female, either postmenopausal, surgically sterile or, for those female subjects of reproductive potential with a non-sterile male partner, willing to use two acceptable contraceptive methods, one of which must be a barrier method, throughout the duration of her participation in the study, i.e., through Week 24.
[Note: For assessing inclusion criterion 3 or 4, a promise to abstain from sexual intercourse is not an acceptable method of preventing pregnancy for the purposes of this protocol. However, subjects who are currently sexually abstinent and who indicate a willingness to use an acceptable contraceptive method(s), as described above, should they begin or resume sexual activity may be enrolled into the study.]
(5) Able to begin study drug dosing within 28 days following HSCT.
(6) Able to ingest and absorb oral medication (in the judgment of the investigator and based on lack of significant GI events/medical history).
[Note: The use of TPN or NPO (nil per os) is not in and of itself exclusionary as long as the reason would not disqualify the subject based on this criterion.]
(7) Willing and able to understand and provide written informed consent.
(8) Willing and able to participate in all required study activities for the entire duration of the study (i.e., through Week 24).