CMX001-351, An Intermediate-size, Expanded Access Protocol to Provide Brincidofovir for the Treatment of Serious Adenovirus Infection or Disease
- Children’s Medical Center (Dallas, Plano, Southlake)
Victor Aquino, M.D.
This expanded access study consists of a screening evaluation to confirm study eligibility and an initial 12-week treatment phase (Day 1 to Week 12) during which subjects will be administered BCV therapy twice-weekly (BiW) for a nominal 24 doses. With the prior approval of the Chimerix medical monitor (or designee), treatment may be extended for up to 12 additional weeks (through Week 24) for subjects whose adV infection has not resolved at the end of the first 12 weeks of treatment, but who have shown clinical improvement on BCV therapy, and in individuals who are deemed by the investigator to be at high risk of recurrence or relapse. a post-treatment follow-up visit will be completed approximately 4 weeks after last BCV administration.
Subjects who will be treated for more than 12 weeks will need to be reconsented before extending treatment. Subjects may not be treated under this protocol for more than 24 weeks. investigators electing to continue BCV therapy for individual patients for more than 24 cumulative weeks may be allowed to continue BCV treatment under a separate emergency investigational new drug application (einD) following application to and receipt of approval from the uS Food and Drug administration (FDa). Subjects who experience a relapse of their adV infection or disease or a new adV infection following completion of the initial 12 weeks of treatment, including during the post-treatment followup period, may also be allowed to resume BCV treatment under a separate einD following application to and receipt of approval from FDa.
Participation in this study will be limited to patients who have not previously been treated with BCV for adV or another double-stranded deoxyribonucleic acid (dsDna) virus in clinical trials or under emergency access regulations, including einD regulations. Patients must also not be eligible for another ongoing controlled clinical trial of BCV.
Subjects must meet all of the following criteria, as applicable, to be eligible to participate in this study:
1. Male or female, aged 2 months and older.
2. AdV positive as detected by either viral culture, cytopathic effect, antigenemia, or histochemistry, or by a positive or detectable AdV DNA PCR value in at least one body fluid or compartment AND symptomatic in at least one of the organ systems specified in Appendix 1 (including fever and abnormal laboratory findings) and, in the opinion of the investigator, those symptoms are at least possibly related to AdV infection.
[Note: Subjects with positive or detectable AdV DNA in plasma or other body fluids or compartments only, i.e., no AdV-related signs and symptoms, will not be allowed to enroll in this study.]
3. Able to ingest and absorb oral medication (in the judgment of the investigator and based on lack of significant gastrointestinal events/medical history).
[Note: The use of total parenteral nutrition or a nil per os designation is not in and of itself exclusionary as long as the underlying reason for either would not disqualify the subject based on this criterion. In addition, with the prior approval of the Chimerix
medical monitor (or designee), subjects who can be dosed using the liquid suspension formulation through a nasogastric tube, gastrostomy tube or other feeding tube that allows the dose of BCV to be delivered directly into the subject[Single Quote]s stomach or duodenum may be enrolled in the study. Intrajejunal delivery of BCV is not advised as PK and tolerability data are not available for this route of administration.]
4. Has not previously been treated with BCV.
5. If a male of reproductive potential, willing to use an acceptable contraceptive method(s) during sexual intercourse with a female partner of reproductive potential throughout the duration of his participation in the study and for at least 6 months after his last dose of BCV.
6. If a female of reproductive potential, i.e., not premenarche, postmenopausal, surgically sterile, or documented ovarian failure, willing to use two acceptable contraceptive methods, one of which must be a barrier method, during sexual intercourse with a
non-sterile male partner, throughout the duration of her participation in the study and for at least 6 months after her last dose of BCV. [Note: For assessing inclusion criterion 5 or 6, a promise to abstain from sexual intercourse is not an acceptable method of preventing pregnancy for the purposes of this study. 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.]
7. Willing and able to understand and provide written informed consent to participate in the study. [Note: If the subject is under 18 years of age or is otherwise unable to legally give his or er informed consent to participate in the study, then written informed consent to participate must be obtained from the parent(s) or legal guardian(s) of the subject or other legal personal representative(s), as applicable. In addition, in the case of minor subjects, the written assent of the subject to participate in the study should be obtained where required by applicable institutional policy on the consenting of minor study participants.]