Pvs230D1-EPA/Matrix-M Vaccine for Malaria

Overseen By Joel A Goldberg, M.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Immunosuppressants, others

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 23

Duration: 2 months

105 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on chronic systemic immunosuppressive medications, you may need to stop them at least 6 months before starting the study.

What data supports the effectiveness of the Pvs230D1-EPA/Matrix-M treatment for malaria?

The research highlights the development of malaria vaccines using protein-based approaches, similar to the Pvs230D1-EPA/Matrix-M treatment, which involves protein antigens and adjuvants (substances that enhance the body's immune response to an antigen). These approaches have shown promise in inducing immune responses against various stages of the malaria parasite's lifecycle, suggesting potential effectiveness for the Pvs230D1-EPA/Matrix-M treatment. ^{1 2 3 4 5}

How is the Pvs230D1-EPA/Matrix-M treatment for malaria different from other treatments?

The Pvs230D1-EPA/Matrix-M treatment is unique because it targets the sexual stage of the malaria parasite in mosquitoes, aiming to block transmission rather than just treating the infection in humans. This approach uses a protein-based vaccine with an adjuvant to enhance immune response, which is different from traditional malaria treatments that focus on killing the parasite in the human host. ^{2 6 7 8 9}

What is the purpose of this trial?

Background: Malaria is a disease carried by mosquitoes in tropical countries around the world. It can cause symptoms like fever, body aches, and weakness. More than half a million people worldwide died of malaria in 2021, mostly children. Researchers want to find ways to prevent the spread of this disease. Objective: To test the effects of a new malaria vaccine. (Volunteers will not be exposed to malaria.) Eligibility: Healthy adults aged 18 to 50 years. Design: Volunteers will be screened. They will have a physical exam with blood and urine tests. They will take a short quiz to make sure they understand the study. Volunteers will have 3 visits to receive the vaccine. These visits will be about 1 month apart. The vaccine will be injected into the muscle of the upper arm. Volunteers will have 12 additional clinic visits. These will start after the first vaccine visit and continue for 8 months. The visits may include a physical exam and blood tests. There will also be 7 follow-up phone calls. These will occur the day after each vaccine visit and then continue for another 12 months. Participants will be asked how they are doing and whether they have had any changes in their health.

Research Team

Joel A Goldberg, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

Healthy adults aged 18-50 who can consent to the study, understand it well, and have reliable access to NIHCC for visits. They must agree to use contraception and not donate blood during the trial. Excluded are pregnant or breastfeeding individuals, those with certain medical conditions or treatments that affect immune function, and anyone planning travel to malaria-endemic areas.

Inclusion Criteria

Individuals of childbearing potential must agree to use an acceptable method of contraception from 1 month prior to enrollment to 1 month after the final vaccination (i.e., from study day -28 until study day 84)

Willing to refrain from donating blood throughout the study until 1 month after the last study visit

Individuals capable of fathering children must agree to use an acceptable method of contraception from 1 month prior to enrollment to 1 month after the final vaccination (i.e., from study day -28 until study day 84)

Exclusion Criteria

Currently pregnant as determined by history or a positive human choriogonadotropin (Beta-hCG) test

I haven't taken strong immune system suppressing drugs for more than 2 weeks in the last 6 months.

Any other finding that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a subject s ability to give informed consent, or increase the risk of having an adverse outcome from participating in the study

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive three doses of the vaccine at 1-month intervals

2 months

3 visits (in-person)

Monitoring

Participants have 12 additional clinic visits for monitoring, including physical exams and blood tests

8 months

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment with follow-up phone calls

12 months

7 follow-up phone calls

Treatment Details

Interventions

• Pvs230D1-EPA/Matrix-M

Trial Overview The trial is testing a new vaccine called Pvs230D1-EPA/Matrix-M designed to prevent the spread of malaria. Participants will receive three injections over several months and attend multiple clinic visits for health checks without being exposed to malaria.

Participant Groups

Group I: Group 3 Experimental Treatment 1 Intervention

50 (micro)g Pvs230D1-EPA/50 (micro)g MM

Group II: Group 2 Experimental Treatment 1 Intervention

25 (micro)g Pvs230D1-EPA/50 (micro)g MM

Group III: Group 1 Experimental Treatment 1 Intervention

5 (micro)g Pvs230D1-EPA/50 (micro)g MM

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

References

1. England pubmed.ncbi.nlm.nih.gov

Vaccines against malaria-still a long way to go. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Recent advances in recombinant protein-based malaria vaccines. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

A phase IIA extension study evaluating the effect of booster vaccination with a fractional dose of RTS,S/AS01E in a controlled human malaria infection challenge. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Vaccination with chemically attenuated Plasmodium falciparum asexual blood-stage parasites induces parasite-specific cellular immune responses in malaria-naïve volunteers: a pilot study. [2019]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Malaria Vaccines: Progress to Date. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Malaria transmission-blocking conjugate vaccine in ALFQ adjuvant induces durable functional immune responses in rhesus macaques. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Preclinical evaluations of Pfs25-EPA and Pfs230D1-EPA in AS01 for a vaccine to reduce malaria transmission. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

A randomised, double-blind, controlled vaccine efficacy trial of DNA/MVA ME-TRAP against malaria infection in Gambian adults. [2018]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Low dose recombinant full-length circumsporozoite protein-based Plasmodium falciparum vaccine is well-tolerated and highly immunogenic in phase 1 first-in-human clinical testing. [2022]