Trial Outcomes & Findings for Safety, Immunogenicity, and Protective Efficacy of Two Regimens of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) During Natural Transmission Season in Healthy African Adults in Mali (NCT NCT03510481)

Last Updated: 2021-08-20

Results Overview

Incidence of local and systemic adverse events (AEs) graded by severity occurring within 7 days after each vaccine administration in year one

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

478 participants

Primary outcome timeframe

Within 7 days after each vaccination in year one

Results posted on

2021-08-20

Participant Flow

478 subjects signed consent. 251 subjects were screen failures. 17 subjects were enrolled but not vaccinated. 210 subjects started the study.

Participant milestones

Participant milestones
Measure	Experimental Arm 1: Dosing Interval 0, 8, 16, and 54 Weeks Participants received 3 doses of PfSPZ Vaccine (9 x10\^5) via direct venous inoculation (DVI) at 0, 8, 16 weeks and a 4th dose at 38 weeks post 3rd vaccination. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.	Experimental Arm 2: Dosing Interval 0, 1, 4, and 42 Weeks Participants received 3 doses of PfSPZ Vaccine (9 x10\^5) via direct venous inoculation (DVI) at 0, 1, 4 weeks and a 4th dose at 38 weeks post 3rd vaccination. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.	Placebo Comparator 3a: Dosing Interval 0, 8, 16, and 54 Weeks Control for Arm 1. Participants received 3 doses of placebo saline injection via direct venous inoculation (DVI) at 0, 8, 16 weeks and a 4th dose at 38 weeks post 3rd injection. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.	Placebo Comparator 3b: Dosing Interval 0, 1, 4, and 42 Weeks Control for Arm 2. Participants received 3 doses of placebo saline injection via direct venous inoculation (DVI) at 0, 1, 4 weeks and a 4th dose at 38 weeks post 3rd injection. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.
Year 1 STARTED	69	70	36	35
Year 1 COMPLETED	56	61	34	31
Year 1 NOT COMPLETED	13	9	2	4
Year 2 - Booster Dose STARTED	46	52	25	19
Year 2 - Booster Dose COMPLETED	42	49	23	18
Year 2 - Booster Dose NOT COMPLETED	4	3	2	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety, Immunogenicity, and Protective Efficacy of Two Regimens of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) During Natural Transmission Season in Healthy African Adults in Mali

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Experimental Arm 1: Dosing Interval 0, 8, 16, and 54 Weeks n=69 Participants Participants received 3 doses of PfSPZ Vaccine (9 x10\^5) via direct venous inoculation (DVI) at 0, 8, 16 weeks and a 4th dose at 38 weeks post 3rd vaccination. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.	Experimental Arm 2: Dosing Interval 0, 1, 4, and 42 Weeks n=70 Participants Participants received 3 doses of PfSPZ Vaccine (9 x10\^5) via direct venous inoculation (DVI) at 0, 1, 4 weeks and a 4th dose at 38 weeks post 3rd vaccination. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.	Placebo Comparator 3a: Dosing Interval 0, 8, 16, and 54 Weeks n=36 Participants Control for Arm 1. Participants received 3 doses of placebo saline injection via direct venous inoculation (DVI) at 0, 8, 16 weeks and a 4th dose at 38 weeks post 3rd injection. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.	Placebo Comparator 3b: Dosing Interval 0, 1, 4, and 42 Weeks n=35 Participants Control for Arm 2. Participants received 3 doses of placebo saline injection via direct venous inoculation (DVI) at 0, 1, 4 weeks and a 4th dose at 38 weeks post 3rd injection. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.	Total n=210 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	69 Participants n=5 Participants	70 Participants n=7 Participants	36 Participants n=5 Participants	35 Participants n=4 Participants	210 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	31 Participants n=7 Participants	10 Participants n=5 Participants	13 Participants n=4 Participants	74 Participants n=21 Participants
Sex: Female, Male Male	49 Participants n=5 Participants	39 Participants n=7 Participants	26 Participants n=5 Participants	22 Participants n=4 Participants	136 Participants n=21 Participants
Race/Ethnicity, Customized Bambara	48 Participants n=5 Participants	43 Participants n=7 Participants	25 Participants n=5 Participants	18 Participants n=4 Participants	134 Participants n=21 Participants
Race/Ethnicity, Customized Bozo	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Malinke	5 Participants n=5 Participants	8 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants	20 Participants n=21 Participants
Race/Ethnicity, Customized Peuhl	3 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	16 Participants n=21 Participants
Race/Ethnicity, Customized Sarakole	6 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	1 Participants n=4 Participants	11 Participants n=21 Participants
Race/Ethnicity, Customized Songrai	3 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	5 Participants n=21 Participants
Race/Ethnicity, Customized Other	4 Participants n=5 Participants	8 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants	23 Participants n=21 Participants
Region of Enrollment Mali	69 participants n=5 Participants	70 participants n=7 Participants	36 participants n=5 Participants	35 participants n=4 Participants	210 participants n=21 Participants

PRIMARY outcome

Timeframe: Within 7 days after each vaccination in year one

Population: The analyses included only subjects who received at least one vaccination

Incidence of local and systemic adverse events (AEs) graded by severity occurring within 7 days after each vaccine administration in year one

Outcome measures

Outcome measures
Measure	Experimental Arm 1: Dosing Interval 0, 8, 16, and 54 Weeks n=69 Participants Participants received 3 doses of PfSPZ Vaccine (9 x 10\^5) via direct venous inoculation (DVI) at 0, 8, 16 weeks and a 4th dose at 38 weeks post 3rd vaccination. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.	Experimental Arm 2: Dosing Interval 0, 1, 4, and 42 Weeks n=70 Participants Participants received 3 doses of PfSPZ Vaccine (9 x 10\^5) via direct venous inoculation (DVI) at 0, 1, 4 weeks and a 4th dose at 38 weeks post 3rd vaccination. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.	Placebo Comparator 3a: Dosing Interval 0, 8, 16, and 54 Weeks n=36 Participants Control for Arm 1. Participants received 3 doses of placebo saline injection via direct venous inoculation (DVI) at 0, 8, 16 weeks and a 4th dose at 38 weeks post 3rd injection. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.	Placebo Comparator 3b: Dosing Interval 0, 1, 4, and 42 Weeks n=35 Participants Control for Arm 2. Participants received 3 doses of placebo saline injection via direct venous inoculation (DVI) at 0, 1, 4 weeks and a 4th dose at 38 weeks post 3rd injection. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.
Number of Participants With Local and Systemic Adverse Events in Year One	39 Participants	27 Participants	19 Participants	11 Participants

PRIMARY outcome

Timeframe: Within 7 days after each vaccination in year two

Population: The analyses included only subjects who received fourth dose of vaccine in year two

Incidence of local and systemic adverse events (AEs) graded by severity occurring within 7 days after vaccine administration during year two (booster dose)

Outcome measures

Outcome measures
Measure	Experimental Arm 1: Dosing Interval 0, 8, 16, and 54 Weeks n=46 Participants Participants received 3 doses of PfSPZ Vaccine (9 x 10\^5) via direct venous inoculation (DVI) at 0, 8, 16 weeks and a 4th dose at 38 weeks post 3rd vaccination. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.	Experimental Arm 2: Dosing Interval 0, 1, 4, and 42 Weeks n=52 Participants Participants received 3 doses of PfSPZ Vaccine (9 x 10\^5) via direct venous inoculation (DVI) at 0, 1, 4 weeks and a 4th dose at 38 weeks post 3rd vaccination. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.	Placebo Comparator 3a: Dosing Interval 0, 8, 16, and 54 Weeks n=25 Participants Control for Arm 1. Participants received 3 doses of placebo saline injection via direct venous inoculation (DVI) at 0, 8, 16 weeks and a 4th dose at 38 weeks post 3rd injection. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.	Placebo Comparator 3b: Dosing Interval 0, 1, 4, and 42 Weeks n=19 Participants Control for Arm 2. Participants received 3 doses of placebo saline injection via direct venous inoculation (DVI) at 0, 1, 4 weeks and a 4th dose at 38 weeks post 3rd injection. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.
Number of Participants With Local and Systemic Adverse Events in Year Two	5 Participants	12 Participants	3 Participants	2 Participants

Adverse Events

Experimental Arm 1: Dosing Interval 0, 8, 16, and 54 Weeks

Serious events: 1 serious events

Other events: 41 other events

Deaths: 0 deaths

Experimental Arm 2: Dosing Interval 0, 1, 4, and 42 Weeks

Serious events: 0 serious events

Other events: 34 other events

Deaths: 0 deaths

Placebo Comparator 3a: Dosing Interval 0, 8, 16, and 54 Weeks

Serious events: 1 serious events

Other events: 20 other events

Deaths: 1 deaths

Placebo Comparator 3b: Dosing Interval 0, 1, 4, and 42 Weeks

Serious events: 0 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Experimental Arm 1: Dosing Interval 0, 8, 16, and 54 Weeks n=69 participants at risk Participants received 3 doses of PfSPZ Vaccine (9 x10\^5) via direct venous inoculation (DVI) at 0, 8, 16 weeks and a 4th dose at 38 weeks post 3rd vaccination. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.	Experimental Arm 2: Dosing Interval 0, 1, 4, and 42 Weeks n=70 participants at risk Participants received 3 doses of PfSPZ Vaccine (9 x10\^5) via direct venous inoculation (DVI) at 0, 1, 4 weeks and a 4th dose at 38 weeks post 3rd vaccination. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.	Placebo Comparator 3a: Dosing Interval 0, 8, 16, and 54 Weeks n=36 participants at risk Control for Arm 1. Participants received 3 doses of placebo saline injection via direct venous inoculation (DVI) at 0, 8, 16 weeks and a 4th dose at 38 weeks post 3rd injection. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.	Placebo Comparator 3b: Dosing Interval 0, 1, 4, and 42 Weeks n=35 participants at risk Control for Arm 2. Participants received 3 doses of placebo saline injection via direct venous inoculation (DVI) at 0, 1, 4 weeks and a 4th dose at 38 weeks post 3rd injection. Oral antimalarial treatment with artemether 20mg/lumefantrine 120mg (AL) given orally with food with 4 tablets taken as a single initial dose, then 4 tabs again after 8hrs, then 4 tabs twice daily for the following two days for a total of 24 tabs, 2 weeks prior to 3rd and 4th injection.
Gastrointestinal disorders Appendicitis	1.4% 1/69 • Number of events 1 • For the primary endpoint, other (non-serious) adverse events were monitored 7 days from time of each vaccination during year one and year two. Deaths and serious AEs were monitored up to 21 months (duration of the study).	0.00% 0/70 • For the primary endpoint, other (non-serious) adverse events were monitored 7 days from time of each vaccination during year one and year two. Deaths and serious AEs were monitored up to 21 months (duration of the study).	0.00% 0/36 • For the primary endpoint, other (non-serious) adverse events were monitored 7 days from time of each vaccination during year one and year two. Deaths and serious AEs were monitored up to 21 months (duration of the study).	0.00% 0/35 • For the primary endpoint, other (non-serious) adverse events were monitored 7 days from time of each vaccination during year one and year two. Deaths and serious AEs were monitored up to 21 months (duration of the study).
Injury, poisoning and procedural complications Road Traffic Accident	0.00% 0/69 • For the primary endpoint, other (non-serious) adverse events were monitored 7 days from time of each vaccination during year one and year two. Deaths and serious AEs were monitored up to 21 months (duration of the study).	0.00% 0/70 • For the primary endpoint, other (non-serious) adverse events were monitored 7 days from time of each vaccination during year one and year two. Deaths and serious AEs were monitored up to 21 months (duration of the study).	2.8% 1/36 • Number of events 1 • For the primary endpoint, other (non-serious) adverse events were monitored 7 days from time of each vaccination during year one and year two. Deaths and serious AEs were monitored up to 21 months (duration of the study).	0.00% 0/35 • For the primary endpoint, other (non-serious) adverse events were monitored 7 days from time of each vaccination during year one and year two. Deaths and serious AEs were monitored up to 21 months (duration of the study).

Other adverse events

Additional Information

Dr. Patrick Duffy

NIAID/LMIV

Phone: 301-761-5089

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee NIAID cannot contact the FDA regarding the trial independent of the IND Sponsor (Sanaria, Inc.). Dr. Patrick Duffy is employed by the clinical sponsor, NIAID (clinical sponsor). Dr. Diawara is not employed by either sponsor.
Publication restrictions are in place

Restriction type: OTHER