Trial Outcomes & Findings for Safety, Immunogenicity and Efficacy of the Blood-stage Plasmodium Vivax Malaria Vaccine Candidate PvDBPII in Matrix M1 (NCT NCT04201431)
NCT ID: NCT04201431
Last Updated: 2024-11-25
Results Overview
Number of volunteers reporting a grade 3 solicited or unsolicited adverse event within 28 days post-vaccination or serious adverse event throughout the study period
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
24 participants
Primary outcome timeframe
12 months
Results posted on
2024-11-25
Participant Flow
Participant milestones
| Measure |
Group 1
Up to 12 volunteers in Group 1 will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at 1, 2 and 12-18 months prior to blood-stage CHMI 2-4 weeks after the third vaccination.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
Group 2
If fewer than 8 volunteers complete the study in Group 1, then new volunteers will be recruited into Group 2, to make up a total of 10 to 12 volunteers who complete 3 vaccinations and CHMI between Groups 1 and 2. Group 2 volunteers will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at monthly intervals, prior to blood-stage CHMI 2-4 weeks after the third vaccination.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
Group 3
Up to 6 volunteers from Group 1 will receive a fourth dose of PvDBPII 50ug/Matrix M1 50ug, at 5 months post the third dose, prior to a second CHMI 2-4 weeks later.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
|---|---|---|---|
|
Vaccinations and Primary CHMI
STARTED
|
12
|
4
|
0
|
|
Vaccinations and Primary CHMI
COMPLETED
|
6
|
4
|
0
|
|
Vaccinations and Primary CHMI
NOT COMPLETED
|
6
|
0
|
0
|
|
4th Vaccination and Secondary CHMI
STARTED
|
0
|
0
|
5
|
|
4th Vaccination and Secondary CHMI
COMPLETED
|
0
|
0
|
5
|
|
4th Vaccination and Secondary CHMI
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Group 1
Up to 12 volunteers in Group 1 will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at 1, 2 and 12-18 months prior to blood-stage CHMI 2-4 weeks after the third vaccination.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
Group 2
If fewer than 8 volunteers complete the study in Group 1, then new volunteers will be recruited into Group 2, to make up a total of 10 to 12 volunteers who complete 3 vaccinations and CHMI between Groups 1 and 2. Group 2 volunteers will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at monthly intervals, prior to blood-stage CHMI 2-4 weeks after the third vaccination.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
Group 3
Up to 6 volunteers from Group 1 will receive a fourth dose of PvDBPII 50ug/Matrix M1 50ug, at 5 months post the third dose, prior to a second CHMI 2-4 weeks later.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
|---|---|---|---|
|
Vaccinations and Primary CHMI
Withdrawal by Subject
|
6
|
0
|
0
|
Baseline Characteristics
Safety, Immunogenicity and Efficacy of the Blood-stage Plasmodium Vivax Malaria Vaccine Candidate PvDBPII in Matrix M1
Baseline characteristics by cohort
| Measure |
Group 1
n=12 Participants
Up to 12 volunteers in Group 1 will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at 1, 2 and 12-18 months prior to blood-stage CHMI 2-4 weeks after the third vaccination.
|
Group 2
n=4 Participants
If fewer than 8 volunteers complete the study in Group 1, then new volunteers will be recruited into Group 2, to make up a total of 10 to 12 volunteers who complete 3 vaccinations and CHMI between Groups 1 and 2. Group 2 volunteers will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at monthly intervals, prior to blood-stage CHMI 2-4 weeks after the third vaccination.
|
Total
n=16 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
30 years
n=5 Participants
|
35 years
n=7 Participants
|
30 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · White
|
11 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Ethnicity · Mixed
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 monthsNumber of volunteers reporting a grade 3 solicited or unsolicited adverse event within 28 days post-vaccination or serious adverse event throughout the study period
Outcome measures
| Measure |
Group 1
n=12 Participants
Up to 12 volunteers in Group 1 will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at 1, 2 and 12-18 months prior to blood-stage CHMI 2-4 weeks after the third vaccination.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
Group 2
n=4 Participants
If fewer than 8 volunteers complete the study in Group 1, then new volunteers will be recruited into Group 2, to make up a total of 10 to 12 volunteers who complete 3 vaccinations and CHMI between Groups 1 and 2. Group 2 volunteers will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at monthly intervals, prior to blood-stage CHMI 2-4 weeks after the third vaccination.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
Group 3
n=5 Participants
Up to 6 volunteers from Group 1 will receive a fourth dose of PvDBPII 50ug/Matrix M1 50ug, at 5 months post the third dose, prior to a second CHMI 2-4 weeks later.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
|---|---|---|---|
|
Safety of the PvDBPII-Matrix M1 Vaccine Candidate, Assessed Through Collection of Data on the Frequency, Duration and Severity of Solicited and Unsolicited Adverse Events.
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: 12 monthsPopulation: Number of participants analyzed corresponds to participants undergoing primary CHMI. (Group 3 participants underwent secondary CHMI and therefore not included in this analysis.)
Assessed by quantitative PCR-derived parasite multiplication rate (PMR). The PMR of the volunteers vaccinated with PvDBPII-Matrix M1 will be compared to the PMR of the malaria-naïve controls partaking in parallel primary CHMI in study VAC069.
Outcome measures
| Measure |
Group 1
n=6 Participants
Up to 12 volunteers in Group 1 will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at 1, 2 and 12-18 months prior to blood-stage CHMI 2-4 weeks after the third vaccination.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
Group 2
n=4 Participants
If fewer than 8 volunteers complete the study in Group 1, then new volunteers will be recruited into Group 2, to make up a total of 10 to 12 volunteers who complete 3 vaccinations and CHMI between Groups 1 and 2. Group 2 volunteers will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at monthly intervals, prior to blood-stage CHMI 2-4 weeks after the third vaccination.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
Group 3
Up to 6 volunteers from Group 1 will receive a fourth dose of PvDBPII 50ug/Matrix M1 50ug, at 5 months post the third dose, prior to a second CHMI 2-4 weeks later.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
|---|---|---|---|
|
Establish Whether the PvDBPII-Matrix M1 Vaccine Can Demonstrate a Reduced Parasite Multiplication Rate in Vaccinated Subjects Compared to Infectivity Controls in a Blood-stage Controlled Human Malaria Infection Model
|
3.2 parasite multiplication rate per 48hr
Interval 2.3 to 4.3
|
6.3 parasite multiplication rate per 48hr
Interval 5.1 to 7.9
|
—
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Peak antibody response at 14 days after the third vaccination in volunteers who received three doses in Group 1 compared to Group 2. Group 3 participants were a subset of 5 participants from Group 1 who went on to complete a fourth vaccination and timepoints after the fourth vaccination are not directly comparable to timepoints after the third vaccination in Group 1 and Group 2 participants.
Total IgG antibody response to the P. vivax Duffy-binding protein (PvDBPII) vaccine
Outcome measures
| Measure |
Group 1
n=8 Participants
Up to 12 volunteers in Group 1 will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at 1, 2 and 12-18 months prior to blood-stage CHMI 2-4 weeks after the third vaccination.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
Group 2
n=4 Participants
If fewer than 8 volunteers complete the study in Group 1, then new volunteers will be recruited into Group 2, to make up a total of 10 to 12 volunteers who complete 3 vaccinations and CHMI between Groups 1 and 2. Group 2 volunteers will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at monthly intervals, prior to blood-stage CHMI 2-4 weeks after the third vaccination.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
Group 3
Up to 6 volunteers from Group 1 will receive a fourth dose of PvDBPII 50ug/Matrix M1 50ug, at 5 months post the third dose, prior to a second CHMI 2-4 weeks later.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
|---|---|---|---|
|
Assessment of the Humoral Immunogenicity of the PvDBPII-Matrix M1 Vaccine Candidate.
|
197.6 μg/mL
Interval 153.1 to 335.3
|
52.64 μg/mL
Interval 20.99 to 101.5
|
—
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Peak T cell response at 14 days after the third vaccination in volunteers who received three doses in Group 1 and Group 2. Group 3 participants were a subset of 5 participants from Group 1 who went on to complete a fourth vaccination and timepoints after the fourth vaccination are not directly comparable to timepoints after the third vaccination in Group 1 and Group 2 participants.
PvDBPII-specific CD4+ CD45RA- CCR7- effector memory T cells producing IFN-γ at 14 days after the third vaccination
Outcome measures
| Measure |
Group 1
n=8 Participants
Up to 12 volunteers in Group 1 will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at 1, 2 and 12-18 months prior to blood-stage CHMI 2-4 weeks after the third vaccination.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
Group 2
n=4 Participants
If fewer than 8 volunteers complete the study in Group 1, then new volunteers will be recruited into Group 2, to make up a total of 10 to 12 volunteers who complete 3 vaccinations and CHMI between Groups 1 and 2. Group 2 volunteers will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at monthly intervals, prior to blood-stage CHMI 2-4 weeks after the third vaccination.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
Group 3
Up to 6 volunteers from Group 1 will receive a fourth dose of PvDBPII 50ug/Matrix M1 50ug, at 5 months post the third dose, prior to a second CHMI 2-4 weeks later.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
|---|---|---|---|
|
Assessment of the Cellular Immunogenicity of the PvDBPII-Matrix M1 Vaccine Candidate.
|
0.2951 percentage of IFN-γ+ cells
Interval 0.056 to 0.914
|
0.04350 percentage of IFN-γ+ cells
Interval 0.014 to 0.058
|
—
|
SECONDARY outcome
Timeframe: 12 monthsCorrelation between anti-PvDBP responses induced by the PvDBPII-Matrix M1 vaccine candidate and PMR.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 12 monthsAssessed by quantitative PCR-derived parasite multiplication rate (PMR). Comparison will be made between volunteers in Group 3 and two control groups: malaria-naive controls undergoing primary CHMI and volunteers undergoing their second CHMI in the parallel VAC069 study (NCT03797989).
Outcome measures
| Measure |
Group 1
n=5 Participants
Up to 12 volunteers in Group 1 will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at 1, 2 and 12-18 months prior to blood-stage CHMI 2-4 weeks after the third vaccination.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
Group 2
If fewer than 8 volunteers complete the study in Group 1, then new volunteers will be recruited into Group 2, to make up a total of 10 to 12 volunteers who complete 3 vaccinations and CHMI between Groups 1 and 2. Group 2 volunteers will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at monthly intervals, prior to blood-stage CHMI 2-4 weeks after the third vaccination.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
Group 3
Up to 6 volunteers from Group 1 will receive a fourth dose of PvDBPII 50ug/Matrix M1 50ug, at 5 months post the third dose, prior to a second CHMI 2-4 weeks later.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
|---|---|---|---|
|
Assess the Durability of Any Reduction in PMR in Group 3 Volunteers Undergoing a Fourth Vaccination and Rechallenge
|
4.3 parasite multiplication rate per 48hr
Interval 3.7 to 5.5
|
—
|
—
|
Adverse Events
Group 1
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Group 2
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Group 3
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Group 1
n=12 participants at risk
Up to 12 volunteers in Group 1 will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at 1, 2 and 12-18 months prior to blood-stage CHMI 2-4 weeks after the third vaccination.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
Group 2
n=4 participants at risk
If fewer than 8 volunteers complete the study in Group 1, then new volunteers will be recruited into Group 2, to make up a total of 10 to 12 volunteers who complete 3 vaccinations and CHMI between Groups 1 and 2. Group 2 volunteers will receive three doses of the PvDBPII 50ug/Matrix M1 50ug candidate vaccine at monthly intervals, prior to blood-stage CHMI 2-4 weeks after the third vaccination.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
Group 3
n=5 participants at risk
Up to 6 volunteers from Group 1 will receive a fourth dose of PvDBPII 50ug/Matrix M1 50ug, at 5 months post the third dose, prior to a second CHMI 2-4 weeks later.
PvDBPII/Matrix-M1: 50ug PvDBPII in 50ug Matrix M1
|
|---|---|---|---|
|
Nervous system disorders
headache
|
41.7%
5/12 • Solicited and unsolicited adverse events were collected for 28 days following each vaccination. Serious adverse events were collected throughout the study duration: up to 29 months for Group 1, 12 months for Group 2 and 30 months for Group 3.
|
50.0%
2/4 • Solicited and unsolicited adverse events were collected for 28 days following each vaccination. Serious adverse events were collected throughout the study duration: up to 29 months for Group 1, 12 months for Group 2 and 30 months for Group 3.
|
0.00%
0/5 • Solicited and unsolicited adverse events were collected for 28 days following each vaccination. Serious adverse events were collected throughout the study duration: up to 29 months for Group 1, 12 months for Group 2 and 30 months for Group 3.
|
|
General disorders
fatigue
|
25.0%
3/12 • Solicited and unsolicited adverse events were collected for 28 days following each vaccination. Serious adverse events were collected throughout the study duration: up to 29 months for Group 1, 12 months for Group 2 and 30 months for Group 3.
|
50.0%
2/4 • Solicited and unsolicited adverse events were collected for 28 days following each vaccination. Serious adverse events were collected throughout the study duration: up to 29 months for Group 1, 12 months for Group 2 and 30 months for Group 3.
|
20.0%
1/5 • Solicited and unsolicited adverse events were collected for 28 days following each vaccination. Serious adverse events were collected throughout the study duration: up to 29 months for Group 1, 12 months for Group 2 and 30 months for Group 3.
|
|
Musculoskeletal and connective tissue disorders
backpain
|
25.0%
3/12 • Solicited and unsolicited adverse events were collected for 28 days following each vaccination. Serious adverse events were collected throughout the study duration: up to 29 months for Group 1, 12 months for Group 2 and 30 months for Group 3.
|
0.00%
0/4 • Solicited and unsolicited adverse events were collected for 28 days following each vaccination. Serious adverse events were collected throughout the study duration: up to 29 months for Group 1, 12 months for Group 2 and 30 months for Group 3.
|
20.0%
1/5 • Solicited and unsolicited adverse events were collected for 28 days following each vaccination. Serious adverse events were collected throughout the study duration: up to 29 months for Group 1, 12 months for Group 2 and 30 months for Group 3.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place