Phase IIa/b Trial of PvCS/Montanide ISA-51 Malaria Vaccine in Adults in Chocó, Colombia
Trial statusNot yet recruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-50
SponsorMalaria Vaccine and Drug Development Center
About this trial
This clinical study will evaluate an investigational malaria vaccine called PvCS/Montanide ISA-51 to determine whether it is safe and whether it can protect adults from infection with Plasmodium vivax, one of the main parasites that causes malaria. P. vivax malaria is common in tropical regions, including Colombia, and can lead to recurrent fever, anemia, and prolonged illness. Currently, no licensed vaccine effectively prevents P. vivax infection.
The investigational vaccine (PvCS) contains synthetic peptides derived from the circumsporozoite (CS) protein located on the surface of P. vivax sporozoites. The vaccine is formulated with the adjuvant Montanide ISA-51 to enhance the immune response. This study aims to assess the safety of the PvCS/Montanide ISA-51 formulation and to determine whether it can prevent malaria after controlled exposure to the parasite.
This is a Phase IIa/b, randomized, double-blind, placebo-controlled clinical trial conducted by the Malaria Vaccine and Drug Development Center (MVDC/CIV) in collaboration with ASOCLINIC IPS and the Pacific Health Institute (INSALPA) in Quibdó, Chocó, Colombia. A total of 72 healthy adults aged 18-50 years from malaria-endemic areas will participate.
Participants will be randomly assigned in a 2:1 ratio to receive either the PvCS/Montanide ISA-51 vaccine or a placebo. The study product will be administered by intramuscular injection at months 0, 2, and 4. After each vaccination, participants will be monitored for side effects and provide blood samples to measure immune responses, including antibody levels and T-cell activity.
Approximately one month after the third vaccination, participants will undergo a controlled human malaria infection (CHMI), during which they will be exposed to P. vivax through the bite of infected mosquitoes under strict medical supervision. Following exposure, participants will be monitored daily using blood tests to detect malaria at the earliest stage.
If malaria parasites are detected-or if 21 days pass without infection-participants will receive prompt, effective antimalarial treatment based on Colombian national guidelines. All participants will continue to be followed for up to 12 months after the challenge to ensure safety and assess long-term outcomes.
Primary goals of the study include:
Determining whether the PvCS/Montanide ISA-51 vaccine prevents P. vivax infection after CHMI.
Measuring the time between exposure and first detection of parasites (pre-patent period).
Evaluating the safety and tolerability of the vaccine.
Secondary goals include:
Measuring immune responses generated by the vaccine. Exploring relationships between immune responses and protection from infection. The total duration of the study is expected to be approximately 30 months, including recruitment, immunizations, challenge procedures, and follow-up. Results will help determine whether this vaccine can safely protect adults against P. vivax malaria and guide planning for future larger-scale vaccine trials in endemic populations.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
None
Disqualifiers
None
Trial design
Design model
Parallel
Treatments tested in this trial
PvCS/Montanide ISA-51 VG Vaccine
Biological/VaccineThe vaccine contains a synthetic peptide representing the central repeat and flanking regions of the Plasmodium vivax circumsporozoite (CS) protein, formulated with Montanide ISA-51 VG (Vaccine Grade), a water-in-oil adjuvant that enhances both antibody and T-cell responses. This formulation is distinct from other malaria vaccine candidates because it specifically targets P. vivax using a synthetic CS peptide antigen, rather than a recombinant protein or viral vector platform. Each 0.5-mL dose is administered intramuscularly in the deltoid at 0, 2, and 4 months. Participants will be closely monitored for safety, reactogenicity, and immunogenicity after each vaccination. Approximately one month after the final dose, volunteers will undergo a controlled human malaria infection (CHMI) via exposure to Anopheles albimanus mosquitoes infected with P. vivax sporozoites to assess protective efficacy.
Placebo - Montanide ISA-51 VG Adjuvant Alone
Biological/VaccineThe placebo consists of Montanide ISA-51 VG (Vaccine Grade) adjuvant without the Plasmodium vivax circumsporozoite (CS) peptide antigen. It is a sterile water-in-oil emulsion prepared and administered in the same manner as the investigational vaccine to maintain blinding. Each 0.5-mL dose is given intramuscularly in the deltoid at 0, 2, and 4 months. The placebo is visually indistinguishable from the vaccine and follows identical handling, storage, and administration procedures. Participants in the placebo group will undergo the same safety monitoring, blood sampling, and controlled human malaria infection (CHMI) one month after the final dose to allow direct comparison of efficacy, safety, and immune responses.
Treatment groups
72 Participants
are divided into 4 treatment groupsGroup A: Naïve Participants - PvCS/Montanide ISA-51 VaccineExperimental treatment 1 intervention
Group B: Naïve Participants - PlaceboPlacebo comparator 1 intervention
Group C: Semi-Immune Participants - PvCS/Montanide ISA-51 VaccineExperimental treatment 1 intervention
Group D: Semi-Immune Participants - PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Protective Efficacy Against P. vivax Infection After Controlled Human Malaria Infection (CHMI)
Definition: Proportion of volunteers who develop P.vivax parasitemia following exposure to 2-4 infected Anopheles albimanus mosquitoes. Parasitemia will be assessed daily by thick blood smear (GG). PCR will be performed as a confirmatory assay but will not to be used for clinical decision-making. Unit of Measure: Number and percentage of infected participants.
Time frame
Day 7 to Day 28 post-challenge.Secondary outcomes
1
Incidence of Local Adverse Events at the Injection and Mosquito Bite Site Within 7 Days Post-Challenge
Number of participants experiencing local adverse events (AEs), including pain, erythema, or swelling, at injection or mosquito bite sites following the challenge, assessed and graded according to FDA Toxicity Grading Scale criteria. Unit: Number of participants with local AEs.
Time frame
Within 7 days post-challenge2
Incidence of Systemic Adverse Events Within 7 Days After Completion of Antimalarial Treatment
Number of participants experiencing local adverse events, including pain, erythema, or swelling, at injection or mosquito bite sites following the challenge, assessed and graded according to FDA Toxicity Grading Scale criteria. Unit: Number of participants with SAEs
Time frame
Within 7 days post-challenge3
Incidence of Serious Adverse Events From First Vaccination Through 12 Months Post-Challenge
Number of participants experiencing serious adverse events (SAEs), as defined by International Council for Harmonisations Good Clinical Practice (ICH-GCP) guidelines, from the first vaccination through 12 months after challenge. Unit: Number of participants with SAEs.
Time frame
From first vaccination through 12 months post-challenge4
Incidence of Laboratory Abnormalities in Hematology and Clinical Chemistry From Baseline to Day 60 Post-Challenge
Number of participants with abnormal hematology or clinical chemistry results, including liver and kidney function tests, graded according to FDA Toxicity Grading Scale criteria, from baseline through Day 60 post-challenge. Unit: Number of participants with abnormal laboratory results.
Time frame
From baseline to Day 60 post-challengeOther outcomes
1
Anti-Plasmodium vivax Circumsporozoite Protein IgG Antibody Titers Measured by ELISA
Quantification of IgG antibody titers against N-terminal, repeat (R), and C-terminal regions of the Plasmodium vivax circumsporozoite protein (PvCSP) measured using enzyme-linked immunosorbent assay (ELISA). Unit: Antibody titer
Time frame
Day 0, Months 1, 2, 3, 6, 7, 8.2
Anti-sporozoite IgG Antibody Titers Measured by Indirect Fluorescent Antibody test (IFAT)
Quantification of IgG antibody titers against Plasmodium vivax sporozoites measured using the indirect fluorescent antibody test (IFAT). Unit: Reciprocal Antibody titer, measured as the highest dilution showing fluorescence.
Time frame
Day 0, Months 1, 2, 3, 6, 7, 8.3
Interferon-Gamma-Producing T-cell Responses Measured by ELISpot Assay
Quantification of interferon-gamma (IFN-γ)-producing T-cell responses measured by ELISpot assay following stimulation with Plasmodium vivax circumsporozoite protein peptides. Unit: Spot-forming cells per number of peripheral blood mononuclear cells (PBMCs)Measured as spot-forming cell (SFCs) per 10\^6PBMCs.
Time frame
Day 0, Month 3, Month 6.4
Time to First Microscopically Detected Parasitemia After Controlled Human Malaria Infection
Number of days from controlled human malaria infection (CHMI) to the first detection of parasitemia by positive thick blood smear. Unit: Days
Time frame
Days 7 to 28 post-challenge.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Malaria Vaccine and Drug Development Center
Lead sponsor
Johns Hopkins University
Collaborator
Source ClinicalTrials.gov
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