Trial Outcomes & Findings for Safety and Efficacy of NF135 CPS Immunization (NCT NCT03813108)

NCT ID: NCT03813108

Last Updated: 2023-05-26

Results Overview

The number of adverse events will be recorded by the trial clinicians for all participants.

Recruitment status

TERMINATED

Study phase

Target enrollment

43 participants

Primary outcome timeframe

Cohort A: Inclusion until 35 days after challenge infection (35 weeks) Cohort B: Inclusion - premature end of study (22 weeks)

Results posted on

2023-05-26

Participant Flow

Participant milestones

Participant milestones
Measure	1: NF135 CPS-immunization Challenged by NF135 10 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes under mefloquine prophylaxis. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. CPS-immunization: Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	2: Low Dose NF135 CPS-immunization Challenged by NF135 10 volunteers will receive three immunizations with 5 NF135.C10 infected Anopheles mosquitoes under mefloquine prophylaxis. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. CPS-immunization: Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	3: NF135 CPS-immunization (A/L) Cohort B 20 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes and are presumptively treated with artemether/lumefantrine starting on day 7 after each immunization. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes. malaria challenge infection, P. falciparum NF135.C10: 10 Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. 10 Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF54 sporozoites. CPS-immunization (A/L): Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes and receive presumptive treatment with artemether/lumefantrine initiated on day 7 after each immunization. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	5: Control Group Challenged by NF135.C10 Cohort A Challenge infection control group: 3 volunteers will receive no immunization and will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.
Overall Study STARTED	10	10	20	3
Overall Study COMPLETED	8	9	0	3
Overall Study NOT COMPLETED	2	1	20	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy of NF135 CPS Immunization

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	1: NF135 CPS-immunization Challenged by NF135 n=10 Participants 10 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes under mefloquine prophylaxis. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. CPS-immunization: Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	2: Low Dose NF135 CPS-immunization Challenged by NF135 n=10 Participants 10 volunteers will receive three immunizations with 5 NF135.C10 infected Anopheles mosquitoes under mefloquine prophylaxis. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. CPS-immunization: Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	3: NF135 CPS-immunization (A/L) Challenged by NF135 Cohorst B n=20 Participants 20 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes and are presumptively treated with artemether/lumefantrine starting on day 7 after each immunization. 10 volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes. 10 volunteers will be challenged by the bites of 5 NF54 infected Anopheles mosquitoes. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. CPS-immunization (A/L): Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes and receive presumptive treatment with artemether/lumefantrine initiated on day 7 after each immunization. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	5: Control Group Challenged by NF135.C10 Cohort A n=3 Participants Challenge infection control group: 3 volunteers will receive no immunization and will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	6: Control Group Challenged by NF54 Cohort B Challenge infection control group: 3 volunteers will receive no immunization and will be challenged by the bites of 5 NF54 infected Anopheles mosquitoes 19 weeks after the last immunization. malaria challenge infection, P. falciparum NF54: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF54 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	7: Control Group Challenged by NF135 Cohort B Challenge infection control group: 3 volunteers will receive no immunization and will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	Total n=43 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	0 Participants n=10 Participants	0 Participants n=115 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants	10 Participants n=7 Participants	20 Participants n=5 Participants	3 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	43 Participants n=115 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	0 Participants n=10 Participants	0 Participants n=115 Participants
Age, Continuous	24 years n=5 Participants	23.5 years n=7 Participants	23.0 years n=5 Participants	21 years n=4 Participants	—	—	23 years n=115 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants	2 Participants n=4 Participants	—	—	23 Participants n=115 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants	1 Participants n=4 Participants	—	—	20 Participants n=115 Participants
Race/Ethnicity, Customized Race · Caucasian	7 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants	3 Participants n=4 Participants	—	—	33 Participants n=115 Participants
Race/Ethnicity, Customized Race · Asian	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	—	—	3 Participants n=115 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants	0 Participants n=4 Participants	—	—	7 Participants n=115 Participants
Region of Enrollment Netherlands	10 participants n=5 Participants	10 participants n=7 Participants	20 participants n=5 Participants	3 participants n=4 Participants	—	—	43 participants n=115 Participants
Body Mass Index (kg/m^2)	23.2 kg/m^2 n=5 Participants	23.7 kg/m^2 n=7 Participants	23.4 kg/m^2 n=5 Participants	22 kg/m^2 n=4 Participants	—	—	23.2 kg/m^2 n=115 Participants
Hemoglobin (mmol/L)	9.3 mmol/L n=5 Participants	9.0 mmol/L n=7 Participants	9.0 mmol/L n=5 Participants	8.3 mmol/L n=4 Participants	—	—	9.0 mmol/L n=115 Participants

PRIMARY outcome

Timeframe: Cohort A: Inclusion until 35 days after challenge infection (35 weeks) Cohort B: Inclusion - premature end of study (22 weeks)

Population: The Control Group Challenged by NF135.C10 Cohort A, was not included in this analysis as it served only as infection control. As subjects in cohort B did not complete their immunizations they were not yet randomized for infection when the trial ended prematurely. Cohort is therefore analyzed as one group that received 1 immunization with 15 NF135.C10 infected mosquitoes under presumptive A/L treatment.

The number of adverse events will be recorded by the trial clinicians for all participants.

Outcome measures

Outcome measures
Measure	1: NF135 CPS-immunization Challenged by NF135 n=10 Participants 10 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes under mefloquine prophylaxis. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. CPS-immunization: Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	2: Low Dose NF135 CPS-immunization Challenged by NF135 n=10 Participants 10 volunteers will receive three immunizations with 5 NF135.C10 infected Anopheles mosquitoes under mefloquine prophylaxis. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. CPS-immunization: Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	3: NF135 CPS-immunization (A/L) Cohort B n=20 Participants 20 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes and are presumptively treated with artemether/lumefantrine starting on day 7 after each immunization. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes. malaria challenge infection, P. falciparum NF135.C10: 10 Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. 10 Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF54 sporozoites. CPS-immunization (A/L): Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes and receive presumptive treatment with artemether/lumefantrine initiated on day 7 after each immunization. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.
Frequency of Adverse Events After NF135.C10 CPS Immunization	139 Adverse events	173 Adverse events	172 Adverse events

PRIMARY outcome

Timeframe: Cohort A: Inclusion until 35 days after challenge infection (35 weeks) Cohort B: Inclusion - premature end of study (22 weeks)

The severity of adverse events will be recorded (mild/moderate/severe) for each adverse event

Outcome measures

Outcome measures
Measure	1: NF135 CPS-immunization Challenged by NF135 n=10 Participants 10 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes under mefloquine prophylaxis. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. CPS-immunization: Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	2: Low Dose NF135 CPS-immunization Challenged by NF135 n=10 Participants 10 volunteers will receive three immunizations with 5 NF135.C10 infected Anopheles mosquitoes under mefloquine prophylaxis. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. CPS-immunization: Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	3: NF135 CPS-immunization (A/L) Cohort B n=20 Participants 20 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes and are presumptively treated with artemether/lumefantrine starting on day 7 after each immunization. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes. malaria challenge infection, P. falciparum NF135.C10: 10 Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. 10 Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF54 sporozoites. CPS-immunization (A/L): Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes and receive presumptive treatment with artemether/lumefantrine initiated on day 7 after each immunization. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.
Magnitude of Adverse Events After NF135.C10 CPS Immunization Severe adverse events (grade 3)	11 Adverse events	10 Adverse events	19 Adverse events
Magnitude of Adverse Events After NF135.C10 CPS Immunization Mild adverse events (grade 1)	108 Adverse events	128 Adverse events	121 Adverse events
Magnitude of Adverse Events After NF135.C10 CPS Immunization Moderate adverse events (grade 2)	20 Adverse events	35 Adverse events	31 Adverse events
Magnitude of Adverse Events After NF135.C10 CPS Immunization Serious adverse events (grade 4)	0 Adverse events	0 Adverse events	1 Adverse events

SECONDARY outcome

Timeframe: Day 1 - 28 after malaria challenge infection (28 days)

Population: The trial was prematurely ended before the challenge infection in cohort B. Only arms that received challenge infection are included in this analysis. In arm 1, 2 subjects withdrew from the trial before challenge infection and 3 subjects were sterily protected and not included in the analysis. In arm 2, 1 subject withdrew from the trial before challenge infection and 2 subjects were sterily protected and not included in this analysis

The effectiveness of CPS-immunization with NF135 sporozoites to protect against malaria challenge infection with homologous N135.C10 or heterologous NF54 sporozoites will be determined by the time to parasitemia in immunized versus non-immunized volunteers after the challenge infection.

Outcome measures

Outcome measures
Measure	1: NF135 CPS-immunization Challenged by NF135 n=5 Participants 10 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes under mefloquine prophylaxis. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. CPS-immunization: Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	2: Low Dose NF135 CPS-immunization Challenged by NF135 n=7 Participants 10 volunteers will receive three immunizations with 5 NF135.C10 infected Anopheles mosquitoes under mefloquine prophylaxis. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. CPS-immunization: Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	3: NF135 CPS-immunization (A/L) Cohort B n=3 Participants 20 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes and are presumptively treated with artemether/lumefantrine starting on day 7 after each immunization. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes. malaria challenge infection, P. falciparum NF135.C10: 10 Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. 10 Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF54 sporozoites. CPS-immunization (A/L): Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes and receive presumptive treatment with artemether/lumefantrine initiated on day 7 after each immunization. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.
Time to Parasitemia	9 days to parasitaemia Interval 7.0 to 11.0	7 days to parasitaemia Interval 7.0 to 11.0	7 days to parasitaemia Interval 7.0 to 7.0

POST_HOC outcome

Timeframe: From day 0 until 28 days after each immunization (28 days)

Population: Only study groups that received NF135.C10 immunizations were included in this analysis. One subject in group 2: Low dose NF135 CPS-immunization challenged by NF135, withdrew consent after the first immunization, and thus did not receive immunization 2 and 3. The study was prematurely terminated, therefore subjects in group 3: NF135 CPS-immunization (A/L) Cohort B only received immunization 1.

Number of subjects that required rescue treatment with atovaquone/proguanil due to a positive thick smear in combination with symptoms following NF135.C10 immunizations despite mefloquine prophylaxis (Cohort A) or presumptive artemether/lumefantrine treatment (Cohort B).

Outcome measures

Outcome measures
Measure	1: NF135 CPS-immunization Challenged by NF135 n=10 Participants 10 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes under mefloquine prophylaxis. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. CPS-immunization: Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	2: Low Dose NF135 CPS-immunization Challenged by NF135 n=10 Participants 10 volunteers will receive three immunizations with 5 NF135.C10 infected Anopheles mosquitoes under mefloquine prophylaxis. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. CPS-immunization: Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	3: NF135 CPS-immunization (A/L) Cohort B n=20 Participants 20 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes and are presumptively treated with artemether/lumefantrine starting on day 7 after each immunization. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes. malaria challenge infection, P. falciparum NF135.C10: 10 Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. 10 Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF54 sporozoites. CPS-immunization (A/L): Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes and receive presumptive treatment with artemether/lumefantrine initiated on day 7 after each immunization. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.
Break Through Infections Break through following immunization 1	10 participants	10 participants	2 participants
Break Through Infections Break through following immunization 2	3 participants	3 participants	—
Break Through Infections Break through following immunization 3	4 participants	5 participants	—

Adverse Events

1: NF135 CPS-immunization Challenged by NF135

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

2: Low Dose NF135 CPS-immunization Challenged by NF135

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

3: NF135 CPS-immunization (A/L) Cohort B

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

5: Control Group Challenged by NF135.C10 Cohort A

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	1: NF135 CPS-immunization Challenged by NF135 n=10 participants at risk 10 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes under mefloquine prophylaxis. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. CPS-immunization: Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	2: Low Dose NF135 CPS-immunization Challenged by NF135 n=10 participants at risk 10 volunteers will receive three immunizations with 5 NF135.C10 infected Anopheles mosquitoes under mefloquine prophylaxis. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. CPS-immunization: Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes while taking mefloquine prophylaxis. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	3: NF135 CPS-immunization (A/L) Cohort B n=20 participants at risk 20 volunteers will receive three immunizations with 15 NF135.C10 infected Anopheles mosquitoes and are presumptively treated with artemether/lumefantrine starting on day 7 after each immunization. Volunteers will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes. malaria challenge infection, P. falciparum NF135.C10: 10 Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. 10 Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF54 sporozoites. CPS-immunization (A/L): Subjects will be immunized 3 times by exposure to the bites of P. falciparum NF135.C10 infected mosquitoes and receive presumptive treatment with artemether/lumefantrine initiated on day 7 after each immunization. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.	5: Control Group Challenged by NF135.C10 Cohort A n=3 participants at risk Challenge infection control group: 3 volunteers will receive no immunization and will be challenged by the bites of 5 NF135.C10 infected Anopheles mosquitoes 19 weeks after the last immunization. malaria challenge infection, P. falciparum NF135.C10: Subjects will receive bites from 5 Anopheles mosquitoes infected with Plasmodium falciparum NF135.C10 sporozoites. Atovaquone / Proguanil Oral Tablet \[Malarone\]: All participants will be treated with atovaquone/proguanil (1000/400 mg (= 4 tablets) 1×/day during 3 consecutive days) when they develop a malaria infection or on day 28 after malaria challenge infection.
Cardiac disorders Acute coronary syndrome	0.00% 0/10 • Groups 1 and 2 (Cohort A ): Inclusion until 35 days after challenge infection (35 weeks) Group 3 (Cohort B): Inclusion until premature end of study (22 weeks) Group 5 (Cohort A): Inclusion until 35 days after challenge infection (5 weeks) As subjects in cohort B did not complete their immunizations, they were not yet randomized for infection when the trial ended prematurely. Cohort B is therefore analyzed as one group that received 1 immunization with 15 NF135.C10 infected mosquitoes under presumptive A/L treatment.	0.00% 0/10 • Groups 1 and 2 (Cohort A ): Inclusion until 35 days after challenge infection (35 weeks) Group 3 (Cohort B): Inclusion until premature end of study (22 weeks) Group 5 (Cohort A): Inclusion until 35 days after challenge infection (5 weeks) As subjects in cohort B did not complete their immunizations, they were not yet randomized for infection when the trial ended prematurely. Cohort B is therefore analyzed as one group that received 1 immunization with 15 NF135.C10 infected mosquitoes under presumptive A/L treatment.	5.0% 1/20 • Number of events 1 • Groups 1 and 2 (Cohort A ): Inclusion until 35 days after challenge infection (35 weeks) Group 3 (Cohort B): Inclusion until premature end of study (22 weeks) Group 5 (Cohort A): Inclusion until 35 days after challenge infection (5 weeks) As subjects in cohort B did not complete their immunizations, they were not yet randomized for infection when the trial ended prematurely. Cohort B is therefore analyzed as one group that received 1 immunization with 15 NF135.C10 infected mosquitoes under presumptive A/L treatment.	0.00% 0/3 • Groups 1 and 2 (Cohort A ): Inclusion until 35 days after challenge infection (35 weeks) Group 3 (Cohort B): Inclusion until premature end of study (22 weeks) Group 5 (Cohort A): Inclusion until 35 days after challenge infection (5 weeks) As subjects in cohort B did not complete their immunizations, they were not yet randomized for infection when the trial ended prematurely. Cohort B is therefore analyzed as one group that received 1 immunization with 15 NF135.C10 infected mosquitoes under presumptive A/L treatment.

Other adverse events

Additional Information

Matthew McCall, MD, PhD

Radboud university medical center

Phone: +3124 3615363

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place