This is a Phase 1b (1b implies that the trial is occurring in a geographic region where cases of the disease against which the vaccine is directed, i.e. Ebola disease, may occur before, during or after the clinical trial), open label, dose-escalation study to examine the safety, tolerability and immunogenicity of an investigational Ebola virus vaccine, cAD3-EB) Z, in Malian healthy adults. The vaccine is a recombinant chimpanzee adenovirus Type-3 vectored Ebola Zaire vaccine (cAd3-EBO Z) and consists of a recombinant replication-deficient adenovirus chimpanzee serotype 3 (cAd3) vector expressing wild-type (WT) Ebola glycoprotein (GP) from the Zaire strain.
A revision of the protocol on 14Dec2014 added a booster dose with MVA-BN® Filo or placebo in 56 subjects in groups 1 (except for first 5 vaccines), 2, 3A and 4. The multivalent vectored vaccine MVA-BN® Filo contains an insert for the Zaire Ebola virus glycoprotein, as well as the Sudan strain Ebola virus glycoprotein, the Musoke strain Marburg virus glycoprotein, and a nucleoprotein from the Tai-Forest Ebola virus.
Forty volunteers will be enrolled into two dosage groups. Another group of 40 volunteers (Groups 3A-C) with group 3A receiving 1.0x10(10)vp. All study participants will receive one dose of the study vaccine by intramuscular injection. Group 4 was added to include another 11 volunteers to receive 1.-X10(11)vp. A total of 91 volunteers have been included.
Group 1 will include 20 participants who will receive the lower dose of the vaccine at 2.5 x 10(10) vp
Group 2 will include 20 participants who will receive the higher does of vaccine at 5 x 10(10) vp.
Group 3A will include 10 participants to receive 1.0X10(10) vp
Group 3B will include 15 participants to receive 2.5X10(10) vp
Group 3C will include 15 participants to receive 5X10(10) vp (participants will be randomly allocated to Group 3B or 3C)
Group 4 will include 11 participants to receive1x10(11) vp. The goal of vaccinating this group is to see if there is any added benefit to the immunogenicity of this vaccine by using a higher dose. This dosage level of the monovalent vaccine has already been studied at VRC/NIH in September and at CVD in Baltimore this month in November. This dosage level was not studied in Oxford nor in Bamako. Having data on West African subjects given this dosage will be very helpful in designing the final formulation for the field trials in Q1 of 2015. The decision will be made based on three sets of data: clinical dose-response; immunologic dose-response (as a proxy for expected protection); and manufacturing yield and cost of goods considerations.
For safety reasons, the first Malian volunteer to receive a vaccine dose in Group 1 will be vaccinated alone and we will wait 24 hours before vaccinating subsequent volunteers in this dose group. Two further Group 1 volunteers may be vaccinated 24 hours after the first, and then at least another 24 hours gap will be left before vaccinating further subjects receiving that dose of vaccine. After 5 volunteers in Group 1 have been vaccinated and followed up for 7 days, an interim safety review (ISR1) will be performed by the DSMB. Enrollment of the rest of this group may proceed only if the DSMB assesses the data and indicates that it is safe to do so.
Group 2 volunteers will be vaccinated without the stepwise procedure. This decision was made by the DSMB after review of safety data for 5X10(10) from the UK trial and approval by the Institutional Review Boards.
Group 3A, who will receive a lower dosage level than Groups 1 or 2, can be vaccinated as soon as logistically possible after all subjects in Group 2 have been vaccinated. Groups 3B and Group 3C will be similarly vaccinated over a period of three days at the rate of 10 subjects per day.
Group 4 will vaccinate and additional 11 participants with 1X10(11) and will be vaccinated over 2 days (5 subjects one day followed by another 6 subjects the next day.
Heterologous boosting dose of MVA-BN® Filo or placebo in 56 subjects in groups 1 (except for first 5 vaccinees), 2, 3A and 4 will commence in January 2015 with random allocation to either vaccine or placebo.
