Trial Outcomes & Findings for Evaluate the Infectivity Equivalence of Current and New Lots of Plasmodium Falciparum Strain NF54 (NCT NCT03882528)

NCT ID: NCT03882528

Last Updated: 2021-03-30

Results Overview

Number of challenged subjects exposed to the new lot of Plasmodium falciparum strain 3D7 parasites developing parasitemia (defined as 2 unambiguous malaria parasites on a single smear).

• Recruitment status: COMPLETED
• Study phase: PHASE1
• Target enrollment: 12 participants
• Primary outcome timeframe: Within 2 weeks
• Results posted on: 2021-03-30

Participant Flow

Participant milestones

Measure	Infective Controls Controlled Human Malaria Infection (CHMI) will consist of exposure to Plasmodium falciparum sporozoites through the bites of infected mosquitoes. Beginning 5 days after the challenge, subjects will be evaluated daily for the development of malaria infection using a blood smear. Plasmodium falciparum malaria parasite: Laboratory cultured Plasmodium falciparum strain 3D7 delivered via the bite of 5 infected mosquitoes with salivary gland scores of at least 2+ (11-100 sporozoites observed).
Overall Study STARTED	12
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluate the Infectivity Equivalence of Current and New Lots of Plasmodium Falciparum Strain NF54

Baseline characteristics by cohort

Measure	Infective Controls n=12 Participants Controlled Human Malaria Infection (CHMI) will consist of exposure to Plasmodium falciparum sporozoites through the bites of infected mosquitoes. Beginning 5 days after the challenge, subjects will be evaluated daily for the development of malaria infection using a blood smear. Plasmodium falciparum malaria parasite: Laboratory cultured Plasmodium falciparum strain 3D7 delivered via the bite of 5 infected mosquitoes with salivary gland scores of at least 2+ (11-100 sporozoites observed).
Age, Customized Age	28.7 years STANDARD_DEVIATION 7.73 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	12 participants n=5 Participants

PRIMARY outcome

Timeframe: Within 2 weeks

Number of challenged subjects exposed to the new lot of Plasmodium falciparum strain 3D7 parasites developing parasitemia (defined as 2 unambiguous malaria parasites on a single smear).

Outcome measures

Measure	Infective Controls n=12 Participants Controlled Human Malaria Infection (CHMI) will consist of exposure to Plasmodium falciparum sporozoites through the bites of infected mosquitoes. Beginning 5 days after the challenge, subjects will be evaluated daily for the development of malaria infection using a blood smear. Plasmodium falciparum malaria parasite: Laboratory cultured Plasmodium falciparum strain 3D7 delivered via the bite of 5 infected mosquitoes with salivary gland scores of at least 2+ (11-100 sporozoites observed).
To Characterize the Infectivity of a New Lot of Plasmodium Falciparum Strain 3D7 Developing Parasitemia Within the Standard WRAIR CHMI Model. 10 Days post-challenge	1 Participants
To Characterize the Infectivity of a New Lot of Plasmodium Falciparum Strain 3D7 Developing Parasitemia Within the Standard WRAIR CHMI Model. 11 Days post-challenge	5 Participants
To Characterize the Infectivity of a New Lot of Plasmodium Falciparum Strain 3D7 Developing Parasitemia Within the Standard WRAIR CHMI Model. 9 Days post-challenge	0 Participants
To Characterize the Infectivity of a New Lot of Plasmodium Falciparum Strain 3D7 Developing Parasitemia Within the Standard WRAIR CHMI Model. 12 Days post-challenge	5 Participants
To Characterize the Infectivity of a New Lot of Plasmodium Falciparum Strain 3D7 Developing Parasitemia Within the Standard WRAIR CHMI Model. 13 Days post-challenge	0 Participants
To Characterize the Infectivity of a New Lot of Plasmodium Falciparum Strain 3D7 Developing Parasitemia Within the Standard WRAIR CHMI Model. 14 Days post-challenge	1 Participants

SECONDARY outcome

Timeframe: Within 2-3 weeks

Time to parasitemia by blood smear method after the P falciparum challenge. Time to parasitemia is defined as the time from CHMI to a first positive malaria parasite result. Parasitemia was defined as the presence of 2 unambiguous malaria parasites on a single smear. Beginning on Day 1 after their challenge, subjects were seen and evaluated daily by a study investigator and blood was drawn for determination of parasitemia by qPCR. Beginning on Day 5 and through Day 19 after their challenge, blood from these daily draws was utilized to generate blood smears to evaluate the development of malaria infection. In addition to smears, subjects were also evaluated for the presence of parasitemia via qPCR. In addition to smears, subjects were also evaluated for the presence of parasitemia via qPCR. However, only blood smears were used for diagnosis during this trial and evaluation of treatment success.

Outcome measures

Measure

Infective Controls n=12 Participants Controlled Human Malaria Infection (CHMI) will consist of exposure to Plasmodium falciparum sporozoites through the bites of infected mosquitoes. Beginning 5 days after the challenge, subjects will be evaluated daily for the development of malaria infection using a blood smear. Plasmodium falciparum malaria parasite: Laboratory cultured Plasmodium falciparum strain 3D7 delivered via the bite of 5 infected mosquitoes with salivary gland scores of at least 2+ (11-100 sporozoites observed).

Diagnostic Efficacy; Time to Parasitemia by Blood Smear Method After the P Falciparum Challenge

11.6 days Standard Deviation 1.00

SECONDARY outcome

Timeframe: Within 2-3 weeks

Time to parasitemia by qPCR method after the P falciparum challenge. Time to parasitemia is defined as the time from CHMI to a first positive malaria parasite result. Parasitemia was defined as the presence of 2 unambiguous malaria parasites on a single smear. On Day 0, subjects were evaluated by qPCR once prior to challenge, to establish a baseline. Beginning on Day 1 through Day 19 after their challenge, subjects were seen and evaluated daily by a study investigator and blood was drawn for determination of parasitemia by qPCR. Beginning on Day 5 and going through Day 19 after their challenge, blood from these daily draws was utilized to generate blood smears to evaluate the development of malaria infection. In addition to smears, subjects were also evaluated for the presence of parasitemia via qPCR. However, only blood smears were used for diagnosis during this trial and evaluation of treatment success.

Outcome measures

Measure

Infective Controls n=12 Participants Controlled Human Malaria Infection (CHMI) will consist of exposure to Plasmodium falciparum sporozoites through the bites of infected mosquitoes. Beginning 5 days after the challenge, subjects will be evaluated daily for the development of malaria infection using a blood smear. Plasmodium falciparum malaria parasite: Laboratory cultured Plasmodium falciparum strain 3D7 delivered via the bite of 5 infected mosquitoes with salivary gland scores of at least 2+ (11-100 sporozoites observed).

Diagnostic Efficacy; Time to Parasitemia (Days) by qPCR Method After the P Falciparum Challenge

7.3 days Standard Deviation 0.65

SECONDARY outcome

Timeframe: Within 6 weeks

Population: Unless previously diagnosed and fully treated, subjects stayed in a hotel starting on the evening of Day 9 post challenge. Subjects diagnosed with malaria were treated on the day parasitemia was detected. Subjects not parasitemic by Day 19 were treated for malaria and released from the hotel. These subjects had clinic daily for completion of treatment and blood collection until treatment efficacy criteria were met. All challenged subjects had a final follow-up visit on Day 28 (±7 days).

Time to Clearance was determined for all subjects for both smear and qPCR. Time to Clearance was defined as the time (in Days) from malaria diagnosis to confirmed clearance of parasitemia. Confirmed clearance of parasitemia by malaria smear was defined as the observation of 3 sequential negative (no parasites observed) daily smears. Confirmed clearance of parasitemia by qPCR was defined as 2 sequential daily (approximately 24 hours apart) negative qPCR assay results. For clarity, the day of the final test in each sequence (smear, PCR) was used as the day of confirmed clearance for calculation purposes.

Outcome measures

Measure	Infective Controls n=12 Participants Controlled Human Malaria Infection (CHMI) will consist of exposure to Plasmodium falciparum sporozoites through the bites of infected mosquitoes. Beginning 5 days after the challenge, subjects will be evaluated daily for the development of malaria infection using a blood smear. Plasmodium falciparum malaria parasite: Laboratory cultured Plasmodium falciparum strain 3D7 delivered via the bite of 5 infected mosquitoes with salivary gland scores of at least 2+ (11-100 sporozoites observed).
Diagnostic Efficacy; Quantification of Parasite Clearance Time (PCT) by Blood Smear and qPCR Methods After Initiation of Antimalarial Treatment qPCR method	3.0 days Standard Deviation 0.60
Diagnostic Efficacy; Quantification of Parasite Clearance Time (PCT) by Blood Smear and qPCR Methods After Initiation of Antimalarial Treatment Blood smear Method	1.2 days Standard Deviation 0.39

Adverse Events

Infective Controls

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Infective Controls n=12 participants at risk Controlled Human Malaria Infection (CHMI) will consist of exposure to Plasmodium falciparum sporozoites through the bites of infected mosquitoes. Beginning 5 days after the challenge, subjects will be evaluated daily for the development of malaria infection using a blood smear. Plasmodium falciparum malaria parasite: Laboratory cultured Plasmodium falciparum strain 3D7 delivered via the bite of 5 infected mosquitoes with salivary gland scores of at least 2+ (11-100 sporozoites observed).
Infections and infestations Malaria	100.0% 12/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected
General disorders Administration site pruritus	66.7% 8/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected
General disorders Administration site erythema	8.3% 1/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected
General disorders Fatigue	16.7% 2/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected
Nervous system disorders Headache	33.3% 4/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected
General disorders Pyrexia	16.7% 2/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected
Gastrointestinal disorders Diarrhea	16.7% 2/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected
Musculoskeletal and connective tissue disorders Myalgia	8.3% 1/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected
Cardiac disorders Tachycardia	16.7% 2/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.3% 1/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected
Skin and subcutaneous tissue disorders Erythema	8.3% 1/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected
Infections and infestations Viral upper respiratory tract infection	8.3% 1/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected
Gastrointestinal disorders Abdominal Pain	8.3% 1/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected
Musculoskeletal and connective tissue disorders Back Pain	8.3% 1/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected
Infections and infestations Influenza	8.3% 1/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected
Investigations Alanine Aminotransferase Elevation	8.3% 1/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected
Nervous system disorders Syncope	8.3% 1/12 • Day 1 through Day 35 Subjects were seen and evaluated daily and adverse event reporting collected

Additional Information

Dr. James Moon, Principal Investigator

Walter Reed Army Institute of Research

Phone: 301-319-9176

Email: James.e.moon.mil@mail.mil

Results disclosure agreements

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