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Trial registered on ANZCTR


Registration number
ACTRN12617000928314
Ethics application status
Approved
Date submitted
21/06/2017
Date registered
27/06/2017
Date last updated
21/07/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled Multiple Ascending Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Brincidofovir Administered Intravenously in Healthy Adult Subjects
Scientific title
A Phase 1, Randomized, Double-Blind, Placebo-Controlled Multiple Ascending Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Brincidofovir Administered Intravenously in Healthy Adult Subjects
Secondary ID [1] 292254 0
none
Universal Trial Number (UTN)
U1111-1198-1151
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
adenovirus 303766 0
cytomegalovirus 303788 0
smallpox 303789 0
Condition category
Condition code
Infection 303133 303133 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
4 cohorts

Intravenous (IV) brincidofovir (BCV) 10 mg or IV placebo administered over 2 hours, twice per week (BIW)-3 active and 1 placebo. Subjects in BIW cohorts will be dosed on Day 1, Day 4, Day 8 and Day 11 (i.e., 1.5 weeks).

IV BCV 20 mg or IV placebo administered over 2 hours, once a week (QW)-6 active and 2 placebo. Subjects in QW cohorts will be dosed on Day 1, Day 8, Day 15, Day 22 (i.e., 3 weeks).

IV BCV 20 mg or IV placebo administered over 1 hour, QW-6 active and 2 placebo. Subjects in QW cohorts will be dosed on Day 1, Day 8, Day 15, Day 22 (i.e., 3 weeks)

IV BCV 20 mg or IV placebo administered over 1 or 2 hours, BIW-6 active and 2 placebo. Subjects in BIW cohorts will be dosed on Day 1, Day 4, Day 8 and Day 11 (i.e., 1.5 weeks). The 1 or 2 hour infusion time will be determined by the Sponsor and Principal Investigator following safety and PK review from previous cohorts.

All doses will be administered in the study clinic and will be recorded in the case report form.
Intervention code [1] 298420 0
Treatment: Drugs
Comparator / control treatment
IV Placebo Glucose 5% or D5W Solution for infusion
All subjects assigned to placebo will receive either Glucose 5% or D5W Solution for Infusion.
Control group
Placebo

Outcomes
Primary outcome [1] 302511 0
To investigate the safety and tolerability following multiple ascending doses of BCV administered IV in healthy adult subjects

Clinical and laboratory safety parameters including: adverse events (AEs), absolute and changes over time of hematology, clinical chemistry, urinalysis, vital signs, and ECG intervals
Timepoint [1] 302511 0
All participants will attend a screening visit up to 4 weeks prior to study start. Screening assessments will include a medical review and physical exam, blood safety tests, drug and alcohol screening, and pregnancy and hormone testing where applicable. Vital signs (blood pressure, pulse, breathing rate, temperature) and ECGs (heart tracings)
will be recorded.

On study details are as follows:
- Once weekly dose groups: Two 2- night stays at clinic and 18 clinic visits, over approximately 36 days.
- Twice weekly dose groups: Two 2-night stays at clinic and 12 clinic visits, over approximately 25 days.

While on study participants will receive trial medication, have blood and urine collected, undergo medical reviews, and have ECGs and vital signs recorded.

Subjects in BIW cohorts will have blood collected on Day -1, 1, 2, 3, 4, 5, 7, 8, 10, 11. 12. 13. 14. 15. 18, 21 and 25; ECGs on Day -1, 1, 4, 8, 11, and 25; Vital Signs on Day -1, 1, 2, 3, 4, 7, 8, 10, 11, 12, and 25.

Subjects in QW cohorts will have blood collected on Day -1, 1, 2, 3, 4, 5, 7, 8, 10, 12, 13, 14, 15, 17, 19, 21, 22, 23, 24, 25, 26, 29, 32, and 36; ECGs on Day -1, 1, 8, 15, 22, and 36; Vital Signs on Day -1, 1, 2, 7, 8, 14, 15, 21. 22, 23, and 36.
Secondary outcome [1] 336274 0
To characterize plasma BCV and cidofovir (CDV) PK, and intracellular (peripheral blood mononuclear cells [PBMCs]) CDV-PP PK following multiple doses of BCV administered IV in healthy adult subjects.

Subjects will be dosed with BCV or placebo. BCV is a lipid conjugate of the nucleotide analog cidofovir (CDV). Following dosing, BCV is converted to CDV and cidofovir diphosphate (CDV-PP), therefore CDV is also measured.


Plasma BCV will be assessed for Cmax, Tmax, Tlag, AUCt, AUClast, AUCinf, %AUCextrap, Clast, Tlast, t1/2, CL, Vz, and Vss following Dose 1 and Dose 4.

Plasma CDV will be assessed for Cmax, Tmax, Tlag, AUCt, AUClast, AUCinf, %AUCextrap, Clast, Tlast, and t1/2 following Dose 1 and Cmax, Tmax, AUCt, and t1/2 following Dose 4.

Intracellular (PBMC) CDV-PP will be assessed for Cmax, Tmax, AUCt, following Dose 1 and Cmax, Tmax, AUCt, and t1/2 following Dose 4.

Plasma BCV, CDV, and intracellular (PBMC) CDV-PP will be assessed for Cmax (Doses 1 and 4), AUCinf (Dose 1) and AUCt (Dose 4) for dose proportionality; if AUCinf is not well estimated AUClast will be subject to dose proportionality assessment.

Plasma BCV, CDV, and intracellular (PBMC) CDV-PP will be assessed for Cmax accumulation ratio (RCmax), observed accumulation ratio (Ro; Dose 4 AUCt/Dose 1 AUCt), predicted accumulation ratio (Rp; Dose 1 AUCinf/Dose 1 AUCt), and steady-state accumulation ratio (Rs; Dose 4 AUCt/Dose 1 AUCinf) where possible.
Timepoint [1] 336274 0
1 hour - BIW - Study Day 1, 11 and 1 hour - QW - Study Day 1, 22: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 168 hours post start if infusion

2 hours - BIW - Study Day 1, 11 and 2 hours - QW - Study Day 1, 22: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 48, 72, and 168 hours post start of infusion

Eligibility
Key inclusion criteria
willing and able to provide written informed consent
vasectomized male or female of non-childbearing potential
non-tobacco/non-nicotine user in the past 6 months
body weight greater than 50kg
BMI from 18-32 kg/m2
no significant medical history
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
child bearing potential
investigational drug or clinical study in past 30 days
positive for HBV, HCV, HIV.
had any infection within past 2 weeks
history of chronic liver disease

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
24/07/2017
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
28
Accrual to date
Final
Recruitment outside Australia
Country [1] 9009 0
New Zealand
State/province [1] 9009 0

Funding & Sponsors
Funding source category [1] 296801 0
Commercial sector/Industry
Name [1] 296801 0
Chimerix, Inc.
Country [1] 296801 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Chimerix, Inc.
Address
2505 Meridian Parkway
Suite 100
Durham, NC 27713
Country
United States of America
Secondary sponsor category [1] 295787 0
None
Name [1] 295787 0
Address [1] 295787 0
Country [1] 295787 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298035 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 298035 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 298035 0
New Zealand
Date submitted for ethics approval [1] 298035 0
23/06/2017
Approval date [1] 298035 0
12/07/2017
Ethics approval number [1] 298035 0
17/NTB/131

Summary
Brief summary
This is the second clinical study administering a new intravenous formulation of BCV. BCV has been studied in hundreds of patients as an oral formulation for the treatment of adenovirus and for the treatment and prevention of cytomegalovirus following stem cell transplantation. This second IV BCV study will investigate the safety and tolerability following multiple ascending doses to healthy subjects to observe how the new formulation compares to placebo and the oral formulations.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 75770 0
Dr Christopher J. Wynne
Address 75770 0
Christchurch Clinical Studies Trust Ltd
PO Box 2856
Christchurch 8140
Country 75770 0
New Zealand
Phone 75770 0
+ 64 3 372 9477
Fax 75770 0
+ 64 3 372 9478
Email 75770 0
[email protected]
Contact person for public queries
Name 75771 0
Jo Sanders
Address 75771 0
Christchurch Clinical Studies Trust Ltd
PO Box 2856
Christchurch 8140
Country 75771 0
New Zealand
Phone 75771 0
+ 64 3 372 9477
Fax 75771 0
+ 64 3 372 9478
Email 75771 0
[email protected]
Contact person for scientific queries
Name 75772 0
Maggie Anderson
Address 75772 0
2505 Meridian Parkway
Suite 100
Durham NC 27713
Country 75772 0
United States of America
Phone 75772 0
+1 919-313-2971
Fax 75772 0
Email 75772 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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