A Phase IIa, Open-label, Multiple Ascending Dose Confirmation Study of the Safety and Tolerability of Intravenous Administration of Brincidofovir in Subjects With Adenovirus Infection or Cytomegalovirus Infection
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- SymBio Pharmaceuticals
- Enrollment
- 53
- Locations
- 11
- Primary Endpoint
- Safety will be evaluated based on incidence and severity of Adverse Events, Serious Adverse Events and laboratory assessments.
Study Overview
Brief Summary
The purpose of this study is to determine the safety and tolerability of intravenous (IV) brincidofovir (BCV; SyB V-1901) 0.2 mg/kg, 0.3 mg/kg or 0.4 mg/kg dosed twice weekly (BIW) or 0.4 mg/kg dosed once weekly (QW) for 4 weeks in subjects with AdV, and IV BCV in subjects with CMV
Detailed Description
This is a Phase IIa, open-label, multiple ascending dose confirmation, multicenter study to evaluate the safety and tolerability of intravenous Brincidofovir (BCV, SyB V-1901) 0.2 mg/kg, 0.3 mg/kg, or 0.4 mg/kg dosed BIW or 0.4 mg/kg dosed QW (Cohorts 1 to 4) in adult and pediatric subjects with AdV viremia, and IV BCV in subjects with CMV.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 2 Months to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male or female, aged 2 months and older at the time of informed consent.
- •AdV DNA viremia >10,000 copies/mL from a single sample, or 2 samples greater than 48 hours apart with the second result higher than the first and both greater than 1000 copies/mL, from the data obtained from the designated central virology laboratory of the local laboratory using the blood sample(s) collected informed consent has been obtained and within 7 days prior to Day 1 (AdV DNA viremia results collected within the 7 day window, but prior to consent may be used if the Informed Consent Form (ICF) signed by the subject provides approval) . CMV viremia with or without evidence of tissue invasive CMV disease. For laboratory results that are generated in units other than copies/mL or IU/mL, please refer to the testing laboratory for guidance on the appropriate conversion calculation.
- •Either (a) have disseminated AdV disease or (b) have an underlying immunocompromised state, and have asymptomatic AdV infection or localized AdV disease.
- •In the judgment of the investigator, be in a serious condition to be treated with intravenous cidofovir for AdV.
Exclusion Criteria
- •Subjects who weigh ≥120 kg.
- •NIH/NCI CTCAE (United States [US] National Institutes of Health [NIH]/National Cancer Institute) Grade 2 or higher diarrhea (i.e., increase of ≥ 4 stools per day over usual pre-transplant stool output) within 7 days prior to Day
- •NIH Stage 4 acute GVHD of the skin (i.e., generalized erythroderma with bullous formation) within 7 days prior to Day
- •NIH Stage 2 or higher acute GVHD of the liver function (i.e., bilirubin >3 mg/dL [SI: >51 μmol/L]) within 7 days prior to Day
- •NIH Stage 2 or higher acute GVHD of the gut (i.e., diarrhea >556 mL/m2/day for pediatric subjects [or >1000 mL/day for young adults as applicable, at centers in the United States only], or severe abdominal pain with or without ileus) within 7 days prior to Day 1.
Arms & Interventions
BCV 0.2mg/kg BIW
BCV: 0.2 mg/kg administered as a continuous IV infusion over 2 hours
Intervention: BCV (Drug)
BCV 0.3mg/kg BIW
BCV: 0.3 mg/kg administered as a continuous IV infusion over 2 hours
Intervention: BCV (Drug)
BCV 0.4 mg/kg BIW
BCV: 0.4 mg/kg administered as a continuous IV infusion over 2 hours
Intervention: BCV (Drug)
BCV 0.4 mg/kg QW
BCV: 0.4 mg/kg administered as a continuous IV infusion over 2 hours
Intervention: BCV (Drug)
0.4 mg/kg BIW
BCV: 0.4 mg/kg administered as a continuous IV infusion over 2 hours
Intervention: BCV (Drug)
0.5 mg/kg BIW
BCV: 0.5 mg/kg administered as a continuous IV infusion over 2 hours
Intervention: BCV (Drug)
0.6 mg/kg BIW
BCV: 0.6 mg/kg administered as a continuous IV infusion over 2 hours
Intervention: BCV (Drug)
Outcomes
Primary Outcomes
Safety will be evaluated based on incidence and severity of Adverse Events, Serious Adverse Events and laboratory assessments.
Time Frame: From initiation of BCV administration up to 19 weeks
Safety will be evaluated based on incidence and severity of Adverse Events, Serious Adverse Events and laboratory assessments.
Antiviral Effects
Time Frame: From initiation of BCV administration up to 9 weeks
Change from baseline AdV viremia in plasma measured on Day 1 and weekly throughout the study.
Secondary Outcomes
No secondary outcomes reported