Comparing Safety and Protective Efficacy of Vaccine Candidate PfSPZ-CVac and MVA ME-TRAP/ ChAd63 ME-TRAP in Adults
1 other identifier
interventional
30
0 countries
N/A
Brief Summary
This is a single centre, randomized, placebo-controlled phase 1/2 study comparing two malaria vaccine candidates. The first vaccine candidate PfSPZ-CVac (Plasmodium falciparum sporozoites (PfSPZ) challenge administered with a chemoprophylactic antimalarial) will be chemoattenuated in vivo with the antimalarial Pyramax. The second vaccine candidate is prime- target vaccination with viral vectored vaccine candidate regime MVA ME-TRAP (Modified Vaccinia Ankara (MVA) multiple epitope thrombosponin-related adhesion protein (ME-TRAP)) and ChAd63 ME-TRAP (Chimpanzee adenovirus 63 (ChAd63). The safety and protective efficacy of both vaccine candidates will be to assessed by controlled human malaria infection with PfSPZ Challenge strain NF54 administered intravenously by syringe.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
Started Jun 2025
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 21, 2022
CompletedFirst Posted
Study publicly available on registry
July 1, 2022
CompletedStudy Start
First participant enrolled
June 1, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2026
December 6, 2024
December 1, 2024
1.1 years
June 21, 2022
December 3, 2024
Conditions
Outcome Measures
Primary Outcomes (1)
Assessment of safety and tolerability of PfSPZ-CVac/Pyramax and MVA ME-TRAP/ChAd63 ME-TRAP
Assessment of all adverse events and serious adverse events that might be related to the administration of PfSPZ-CVac/Pyramax and MVA ME-TRAP/ChAd63 ME-TRAP
From the first administration until the last follow-up visit (Group 1: day 136, Group 2: day 82)
Secondary Outcomes (1)
Assessment of protective efficacy of PfSPZ-CVac/Pyramax and of MVA ME-TRAP /ChAd63 ME-TRAP in healthy, malaria-naïve adults against homologous CHMI with PfSPZ Challenge (NF54) by DVI
From administration of CHMI (Group 1:day 113, Group 2: 59) until the last follow-up visit (Group 1: day 136, Group 2: day 82)
Other Outcomes (2)
Assessment of Pyramax as a drug for in vivo chemoattenuation of PfSPZ Challenge (NF54) for the PfSPZ-CVac approach
From the first administration (day 1) until the last follow-up visit (Group 1: day 136)
Assessment of the immunogenicity of each of the malaria vaccine candidates
From the first administration until the last follow-up visit (Group 1: day 136, Group 2: day 82)
Study Arms (3)
PfSPZ-CVac/Pyramax
EXPERIMENTAL200.000 PfSPZ of PfSPZ Challenge NF54 will be administered by DVI along with one weight-adjusted oral dose of Pyramax each on day 1, day 6, and day 29
MVA ME-TRAP/ChAd63 ME-TRAP
EXPERIMENTALMVA ME-TRAP 1.5 x 10\^8 pfu will be administered intramuscularly on day 1 for priming. ChAd63 ME-TRAP 5 x 10\^10 vp will subsequently administered by DVI on day 29.
Saline/placebo pill
PLACEBO COMPARATORAs placebo comparator to PfSPZ-CVac/Pyramax, saline will be administered intravenously along with an oral placebo pill on day 1, day 6, and day 29. As placebo comparator to MVA ME-TRAP/ChAd63 ME-TRAP, saline will be administered intramuscularly on day 1 and intravenously on day 29. No placebo pill will be used to compare to the arm MVA ME-TRAP/ChAd63 ME-TRAP.
Interventions
Combination drug for treatment of uncomplicated malaria
cryopreserved Plasmodium falciparum sporozoites injected by intravenous inoculation
virally vectored subunit vaccine candidates where ME-TRAP is expressed by the non-replicating viral vector Modified Vaccinia Ankara (MVA)
virally vectored subunit vaccine candidates where ME-TRAP is expressed by the non-replicating viral vector Chimpanzee Adenovirus 63 (ChAd63)
0.9% NaCl solution for injection
Eligibility Criteria
You may qualify if:
- Able and willing (in the Investigator's opinion) to comply with all study requirements.
- Willing to allow the investigators to discuss the volunteer's medical history with their general practitioner if required.
- Residence in Tübingen or surroundings for the period of the trial.
- Women only: Must agree to practice continuous highly effective contraception for the duration of the study and until the end of relevant systemic exposure (a method which results in a low failure rate; i.e. less than 1% per year). Additionally, women will only be exposed to the PfSPZ-CVac/ME-TRAP products following a negative highly sensitive pregnancy test the day before immunization/CHMI.
- Agreement to refrain from blood donation during the course of the study and after the end of their involvement in the study according to the local and national blood banking eligibility criteria (which is a permanent refrain from blood donations after a malaria parasite infection).
- Provision of written informed consent to receive PfSPZ Challenge products or ME-TRAP products for immunization and subsequently for CHMI.
- Accept to be contacted (24/7) by mobile phone during the immunization and CHMI period.
- Willingness to take Pyramax during immunization (PfSPZ-CVac group) and a curative antimalarial regimen following CHMI.
- Agreement to stay overnight for observation during the period of intensive follow-up post-challenge if required.
- Answer all questions on the informed consent quiz correctly.
- A body mass index \<35
You may not qualify if:
- History of P. falciparum malaria within the last 5 years.
- Prior receipt of malaria vaccine.
- Planned travel to malaria endemic areas during the study period.
- Use of drugs with known antimalarial activity within 30 days of study enrollment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones, or azithromycin).
- Participation in other clinical trials or the intake of an investigational medicinal product within the last 90 days or planned receipt during the duration of this study
- Human Immunodeficiency Virus (HIV) infection.
- Any confirmed or suspected immunosuppressive or immunodeficient state (e.g. repeated and/or unusual infections), history of infection caused by opportunistic organisms any infection or combination of infections that suggest underlying immunodeficiency, history of meningitis, encephalitis, septic shock, life-threatening soft tissue infection, more than one pneumonia, asplenia and/or chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)).
- Use of immunoglobulins or blood products within 3 months prior to enrollment.
- Known (or signs consistent with) sickle cell anaemia, sickle cell trait, thalassemia or thalassemia trait, glucose-6-phosphate dehydrogenase deficiency.
- Pregnancy, lactation or intention to become pregnant during the study.
- Contraindications to the use of the following antimalarial medications: Atovaquone-proguanil, artemether-lumefantrine, artesunate, pyronaridine-artesunate, i.e.:
- Known hypersensitivity to any of these drugs
- intake of the following drugs: rifampicine, rifabutin, metoclopramide, warfarin, cumarine-derivatives, etoposide, antiretroviral drugs, imipramine, amytriptilin, clomipramin, carbamazepine, phenytoin, St. Johns wort, metoprolol, flecainide, propafenone, digoxin, dabigatran; drugs inducing QTc prolongation, drugs metabolized by CYP2D6, drugs inducing CAP3A4.
- History of allergic disease or reactions likely to be exacerbated by any component of the vaccine (e.g. egg products, Kathon).
- History of clinically significant contact dermatitis.
- +16 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University Hospital Tuebingenlead
- Sanaria Inc.collaborator
- University of Oxfordcollaborator
Related Publications (1)
Sulyok Z, Fendel R, Eder B, Lorenz FR, Kc N, Karnahl M, Lalremruata A, Nguyen TT, Held J, Adjadi FAC, Klockenbring T, Flugge J, Woldearegai TG, Lamsfus Calle C, Ibanez J, Rodi M, Egger-Adam D, Kreidenweiss A, Kohler C, Esen M, Sulyok M, Manoj A, Richie TL, Sim BKL, Hoffman SL, Mordmuller B, Kremsner PG. Heterologous protection against malaria by a simple chemoattenuated PfSPZ vaccine regimen in a randomized trial. Nat Commun. 2021 May 4;12(1):2518. doi: 10.1038/s41467-021-22740-w.
PMID: 33947856BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Sabine Bélard, Dr.
University Hospital Tuebingen
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- FACTORIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 21, 2022
First Posted
July 1, 2022
Study Start
June 1, 2025
Primary Completion (Estimated)
June 30, 2026
Study Completion (Estimated)
June 30, 2026
Last Updated
December 6, 2024
Record last verified: 2024-12