Active — Not RecruitingPhase 1

First-in-Human PfSPZ-LARC2 Vaccination/CHMI

United States22 participantsStarted 2025-07-23

Plain-language summary

This randomized, double-blind, placebo-controlled, Phase 1 trial will enroll up to 22 malaria-naïve, adult participants to test safety, tolerability, immunogenicity, and efficacy of the genetically attenuated Plasmodium falciparum sporozoite vaccine (PfSPZ-LARC2) Vaccine. PfSPZ-LARC2 Vaccine is a late-arresting, replication-competent whole Plasmodium falciparum sporozoite product. We hypothesize that the PfSPZ-LARC2 Vaccine will be safe from breakthrough infection by virtue of deletion of two key parasite genes Mei2 and LINUP and may be more immunogenic and protective than previously tested early arresting sporozoite vaccines. The primary objective is to assess the tolerability and safety of administration of PfSPZ-LARC2 Vaccine, with special attention to the adequacy of attenuation.

Who can participate

Age range18 Years – 45 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Provides written informed consent prior to the initiation of any study procedures.
✓. Able to understand and agrees to adhere to all planned study procedures and be available for all study visits.
✓. Male or non-pregnant female, 18 to 45 years of age (inclusive) at time of enrollment.
✓. BMI 18.0-35.0 kg/m\^2 at screening.
✓. Females of childbearing potential\* must agree to use or have practiced true abstinence\*\* or use at least one acceptable primary form of contraception\*\*\*,\*\*\*\*,\*\*\*\*\* Note: These criteria are applicable to females in a heterosexual relationship and child-bearing potential (i.e., the criteria do not apply to participants in a same sex relationship).
✓. Females of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to enrollment.
✓. Males of childbearing potential: use condoms with a female partner of childbearing potential from their enrollment visit (Visit 1), to 60 days after last vaccination or 28 days post-Controlled Human Malaria Infection (CHMI), whichever is later.\*,\*\*
✓. Male participants agree to refrain from sperm donation from the time of first vaccination until 60 days after the last vaccination or until 28 days post-CHMI, whichever is later.

What they're measuring

Occurrence of Grade 3 laboratory toxicities related to vaccination

Timeframe: Through 14 days after the last vaccination

Occurrence of serious adverse events (SAEs) considered related to vaccination

Timeframe: Through 180 days post-CHMI

Occurrence of solicited local adverse events (AEs) related to the vaccine

Timeframe: Through 6 days after each vaccination

Occurrence of solicited systemic adverse events (AEs) related to the vaccine

Timeframe: Through 6 days after each vaccination

Occurrence of unsolicited adverse events (AEs) considered related to vaccination

Timeframe: Through 28 days after the last vaccination

Proportion of participants with breakthrough blood-stage infection

Timeframe: Through 28 days after last vaccination

Solicited systemic adverse event (AE) related to the breakthrough infections

Timeframe: Through 28 days after each vaccination

Trial details

NCT IDNCT06735209

SponsorNational Institute of Allergy and Infectious Diseases (NIAID)

Sponsor typeNIH

Study typeINTERVENTIONAL

Primary completion2027-02-01

View on ClinicalTrials.gov More Malaria trials

Plain-language summary

Who can participate

Age range18 Years – 45 Years

SexALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion criteria

✓. Provides written informed consent prior to the initiation of any study procedures.
✓. Able to understand and agrees to adhere to all planned study procedures and be available for all study visits.
✓. Male or non-pregnant female, 18 to 45 years of age (inclusive) at time of enrollment.
✓. BMI 18.0-35.0 kg/m\^2 at screening.
✓. Females of childbearing potential\* must agree to use or have practiced true abstinence\*\* or use at least one acceptable primary form of contraception\*\*\*,\*\*\*\*,\*\*\*\*\* Note: These criteria are applicable to females in a heterosexual relationship and child-bearing potential (i.e., the criteria do not apply to participants in a same sex relationship).
✓. Females of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to enrollment.
✓. Males of childbearing potential: use condoms with a female partner of childbearing potential from their enrollment visit (Visit 1), to 60 days after last vaccination or 28 days post-Controlled Human Malaria Infection (CHMI), whichever is later.\*,\*\*
✓. Male participants agree to refrain from sperm donation from the time of first vaccination until 60 days after the last vaccination or until 28 days post-CHMI, whichever is later.

What they're measuring

Occurrence of Grade 3 laboratory toxicities related to vaccination

Timeframe: Through 14 days after the last vaccination

Occurrence of serious adverse events (SAEs) considered related to vaccination

Timeframe: Through 180 days post-CHMI

Occurrence of solicited local adverse events (AEs) related to the vaccine

Timeframe: Through 6 days after each vaccination

Occurrence of solicited systemic adverse events (AEs) related to the vaccine

Timeframe: Through 6 days after each vaccination

Occurrence of unsolicited adverse events (AEs) considered related to vaccination

Timeframe: Through 28 days after the last vaccination

Proportion of participants with breakthrough blood-stage infection

Timeframe: Through 28 days after last vaccination

Solicited systemic adverse event (AE) related to the breakthrough infections

Timeframe: Through 28 days after each vaccination

First-in-Human PfSPZ-LARC2 Vaccination/CHMI

Plain-language summary

Who can participate

Inclusion criteria

What they're measuring

Trial details

First-in-Human PfSPZ-LARC2 Vaccination/CHMI

Plain-language summary

Who can participate

Inclusion criteria

What they're measuring

Trial details

Exclusion criteria