Trial Outcomes & Findings for VAC071: A Study to Assess Efficacy of the ChAd63/MVA PvDBP Vaccines (NCT NCT04009096)

NCT ID: NCT04009096

Last Updated: 2024-04-12

Results Overview

Quantitative PCR-derived parasite multiplication rate (PMR) will be the primary efficacy endpoint and a comparison of the endpoint between Groups 1, 2 and 3 (pooled data) and malaria-naïve controls partaking in simultaneous CHMI, under identical conditions, will constitute the primary analysis for efficacy.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 16 participants
• Primary outcome timeframe: 3 months post CHMI
• Results posted on: 2024-04-12

Participant Flow

Participant milestones

Measure	Group 1 3 volunteers receiving 5 x 10\^10 vp ChAd63 PvDBP and 2 x 10\^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen, followed by blood-stage CHMI 2-4 weeks later.	Group 2 Up to 10 volunteers receiving one dose of 5 x 10\^10 vp ChAd63 PvDBP, 12-18 months later receiving a second dose of 5 x 10\^10 vp ChAd63 PvDBP and 8 weeks later 2 x 10\^8 pfu MVA PvDBP, followed by blood-stage CHMI 2-4 weeks later.	Group 3 If fewer than 6 volunteers complete the study in Group 2, then new volunteers will be recruited into Group 3, to make up a total of 6 volunteers between Groups 2 and 3 who complete all vaccinations and CHMI. Volunteers in Group 3 will receive 5 x 10\^10 vp ChAd63 PvDBP and 2 x10\^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen, followed by blood-stage CHMI 2-4 weeks later.
Overall Study STARTED	3	10	3
Overall Study COMPLETED	3	2	3
Overall Study NOT COMPLETED	0	8	0

Reasons for withdrawal

Measure	Group 1 3 volunteers receiving 5 x 10\^10 vp ChAd63 PvDBP and 2 x 10\^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen, followed by blood-stage CHMI 2-4 weeks later.	Group 2 Up to 10 volunteers receiving one dose of 5 x 10\^10 vp ChAd63 PvDBP, 12-18 months later receiving a second dose of 5 x 10\^10 vp ChAd63 PvDBP and 8 weeks later 2 x 10\^8 pfu MVA PvDBP, followed by blood-stage CHMI 2-4 weeks later.	Group 3 If fewer than 6 volunteers complete the study in Group 2, then new volunteers will be recruited into Group 3, to make up a total of 6 volunteers between Groups 2 and 3 who complete all vaccinations and CHMI. Volunteers in Group 3 will receive 5 x 10\^10 vp ChAd63 PvDBP and 2 x10\^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen, followed by blood-stage CHMI 2-4 weeks later.
Overall Study Withdrawal by Subject	0	7	0
Overall Study Physician Decision	0	1	0

Baseline Characteristics

VAC071: A Study to Assess Efficacy of the ChAd63/MVA PvDBP Vaccines

Baseline characteristics by cohort

Measure	Group 1 n=3 Participants 3 volunteers receiving 5 x 10\^10 vp ChAd63 PvDBP and 2 x 10\^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen, followed by blood-stage CHMI 2-4 weeks later.	Group 2 n=10 Participants Up to 10 volunteers receiving one dose of 5 x 10\^10 vp ChAd63 PvDBP, 12-18 months later receiving a second dose of 5 x 10\^10 vp ChAd63 PvDBP and 8 weeks later 2 x 10\^8 pfu MVA PvDBP, followed by blood-stage CHMI 2-4 weeks later.	Group 3 n=3 Participants If fewer than 6 volunteers complete the study in Group 2, then new volunteers will be recruited into Group 3, to make up a total of 6 volunteers between Groups 2 and 3 who complete all vaccinations and CHMI. Volunteers in Group 3 will receive 5 x 10\^10 vp ChAd63 PvDBP and 2 x10\^8 pfu MVA PvDBP 8 weeks later, in a heterologous prime-boost regimen, followed by blood-stage CHMI 2-4 weeks later.	Total n=16 Participants Total of all reporting groups
Age, Continuous	32 years n=5 Participants	28 years n=7 Participants	25 years n=5 Participants	28 years n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	9 Participants n=4 Participants
Race/Ethnicity, Customized White	3 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	13 Participants n=4 Participants
Race/Ethnicity, Customized Arab	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment United Kingdom	3 participants n=5 Participants	10 participants n=7 Participants	3 participants n=5 Participants	16 participants n=4 Participants

PRIMARY outcome

Timeframe: 3 months post CHMI

Population: Primary efficacy analysis conducted as per protocol on pooled data from all volunteers across groups 1, 2 and 3 who underwent CHMI. Numbers in each group too small for meaningful summary statistics to be reported for each group separately.

Quantitative PCR-derived parasite multiplication rate (PMR) will be the primary efficacy endpoint and a comparison of the endpoint between Groups 1, 2 and 3 (pooled data) and malaria-naïve controls partaking in simultaneous CHMI, under identical conditions, will constitute the primary analysis for efficacy.

Outcome measures

Measure	Groups 1, 2 and 3 Volunteers Completing CHMI n=8 Participants Pooled data of all volunteers in Groups 1, 2 and 3 who underwent CHMI	Following MVA PvDBP Vaccination Volunteers who received vaccination with MVA PvDBP
Efficacy of the ChAd63 and MVA PvDBP Vaccines, Administered in a Heterologous Prime-boost Regimen, Assessed by a Reduced Parasite Multiplication Rate in Vaccinated Subjects	5.4 parasite multiplication rate per 48hr Interval 4.0 to 7.3	—

SECONDARY outcome

Timeframe: Within 28 days following each vaccination. Vaccinations occurred at 0 and 2 months in Groups 1 and 3 (ChAd63, MVA PvDBP); and at 0, 17 and 19 months in Group 2 (ChAd63, ChAd63, MVA PvDBP).

Population: Adverse events following vaccinations are analysed by IMP administered

No of participants reporting adverse event

Outcome measures

Measure	Groups 1, 2 and 3 Volunteers Completing CHMI n=16 Participants Pooled data of all volunteers in Groups 1, 2 and 3 who underwent CHMI	Following MVA PvDBP Vaccination n=8 Participants Volunteers who received vaccination with MVA PvDBP
Safety of the ChAd63 and MVA PvDBP Vaccines Andidates, Administered in a Heterologous Prime-boost Regimen in a CHMI Study in Healthy Volunteers Any grade 3 solicited adverse event	1 Participants	2 Participants
Safety of the ChAd63 and MVA PvDBP Vaccines Andidates, Administered in a Heterologous Prime-boost Regimen in a CHMI Study in Healthy Volunteers Any grade 3 unsolicited adverse event	0 Participants	0 Participants
Safety of the ChAd63 and MVA PvDBP Vaccines Andidates, Administered in a Heterologous Prime-boost Regimen in a CHMI Study in Healthy Volunteers Any grade 3 laboratory adverse event	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 14 days after the final vaccination. Final vaccinations (MVA PvDBP) occurred at 2 months in Groups 1 and 3; and at 19 months in Group 2.

Population: Immunological analysis conducted as per protocol on pooled data from all volunteers across groups 1, 2 and 3 who completed vaccinations. Numbers in each group too small for meaningful summary statistics to be reported for each group separately.

Total IgG antibody response to the P. vivax Duffy-binding protein (PvDBP)

Outcome measures

Measure	Groups 1, 2 and 3 Volunteers Completing CHMI n=8 Participants Pooled data of all volunteers in Groups 1, 2 and 3 who underwent CHMI	Following MVA PvDBP Vaccination Volunteers who received vaccination with MVA PvDBP
The Humoral Immunogenicity ChAd63 and MVA PvDBP Vaccine Candidates, Administered in a Heterologous Prime-boost Regimen	29 μg/mL Interval 9.0 to 85.0	—

SECONDARY outcome

Timeframe: 14 days after the final vaccination. Final vaccinations (MVA PvDBP) occurred at 2 months in Groups 1 and 3 ; and at 19 months in Group 2.

Population: Immunological analysis conducted as per protocol on pooled data from all volunteers across groups 1, 2 and 3 who completed vaccinations. Numbers in each group too small for meaningful summary statistics to be reported for each group separately.

PvDBPII-specific CD4+ CD45RA- CCR7- effector memory T cells producing IFN-γ

Outcome measures

Measure	Groups 1, 2 and 3 Volunteers Completing CHMI n=8 Participants Pooled data of all volunteers in Groups 1, 2 and 3 who underwent CHMI	Following MVA PvDBP Vaccination Volunteers who received vaccination with MVA PvDBP
The Cellular Immunogenicity ChAd63 and MVA PvDBP Vaccine Candidates, Administered in a Heterologous Prime-boost Regimen	0.6825 Percentage of IFN-γ+ cells Interval 0.095 to 1.951	—

SECONDARY outcome

Timeframe: 3 months post CHMI

Statistical correlation between anti-PvDBP antibody responses induced by the ChAd63 and MVA PvDBP vaccines and PMR.

Outcome measures

Outcome data not reported

Adverse Events

Following ChAd63 PvDBP Vaccination

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Following MVA PvDBP Vaccination

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	Following ChAd63 PvDBP Vaccination n=16 participants at risk Volunteers who received at least one dose of ChAd63 PvDBP	Following MVA PvDBP Vaccination n=8 participants at risk Volunteers who received vaccination with MVA PvDBP
Reproductive system and breast disorders Dysmenorrhoea	12.5% 2/16 • Data on solicited adverse events were collected for 7 days after vaccination and unsolicited adverse events for 28 days post-vaccination. Serious adverse events were collected for the study duration: up to 12 months for Group 1 and 3 participants, and up to 29 months for Group 2 participants. Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever	0.00% 0/8 • Data on solicited adverse events were collected for 7 days after vaccination and unsolicited adverse events for 28 days post-vaccination. Serious adverse events were collected for the study duration: up to 12 months for Group 1 and 3 participants, and up to 29 months for Group 2 participants. Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever
General disorders Feverish	0.00% 0/16 • Data on solicited adverse events were collected for 7 days after vaccination and unsolicited adverse events for 28 days post-vaccination. Serious adverse events were collected for the study duration: up to 12 months for Group 1 and 3 participants, and up to 29 months for Group 2 participants. Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever	12.5% 1/8 • Data on solicited adverse events were collected for 7 days after vaccination and unsolicited adverse events for 28 days post-vaccination. Serious adverse events were collected for the study duration: up to 12 months for Group 1 and 3 participants, and up to 29 months for Group 2 participants. Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever
General disorders Fever	0.00% 0/16 • Data on solicited adverse events were collected for 7 days after vaccination and unsolicited adverse events for 28 days post-vaccination. Serious adverse events were collected for the study duration: up to 12 months for Group 1 and 3 participants, and up to 29 months for Group 2 participants. Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever	12.5% 1/8 • Data on solicited adverse events were collected for 7 days after vaccination and unsolicited adverse events for 28 days post-vaccination. Serious adverse events were collected for the study duration: up to 12 months for Group 1 and 3 participants, and up to 29 months for Group 2 participants. Following each vaccination, volunteers completed an electronic diary card for 28 days with adverse event data. Solicited AEs, collected for 7 days, included local AEs (pain, erythema, warmth, swelling and itching) and systemic AEs (headache, malaise, myalgia, arthralgia, feverishness, nausea, fatigue, and measured fever

Additional Information

Dr. Angela Minassian

University of Oxford

Phone: 01865611425

Email: angela.minassian@ndm.ox.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place