MalariaPhase 1NCT02704533
Sequential Optimization of Dose and Schedule of PfSPZ Vaccine
A Phase 1 study testing PfSPZ Vaccine, PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8) in people with Malaria, run by Sanaria Inc. at 1 site in Germany.
Trial summary
MAVACHE is a sequential dose and schedule optimization trial of intravenous immunization with PfSPZ Vaccine in 18 to 54 malaria-naïve, healthy adult volunteers receiving 9x10^5, 1.35x10^6, or 2.7x10^6 PfSPZ per dose and a total dose between 2.7x10^6 and 8.1x10^6 PfSPZ followed by CHMI with 3,200 fully infectious PfSPZ… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- PfSPZ Vaccine, PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteGermany
- Study dates
- 29 Aug 2016to Dec 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adults aged 18 to 45 years
- 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 ('Hausarzt' in German) if required
- Residence in Tübingen or surroundings for the period of the trial
- Women only: Must agree to practice continuous effective contraception for the duration of the study (a method which results in a failure rate less than 1% per year)
- 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 (currently there is a four year restriction in Germany)
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- Written informed consent to receive PfSPZ products:
- Optimization phase: PfSPZ Vaccine for immunization and PfSPZ Challenge (NF54) for CHMI
- PfSPZ Challenge (7G8) dose finding: PfSPZ Challenge (7G8) for CHMI
- Verification phase: PfSPZ Vaccine for immunization, PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8) for CHMI
- Reachable (24/7) by mobile phone during the immunization and CHMI period
- Willingness to take 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
Who cannot join
- History of P. falciparum malaria
- Planned travel to malaria endemic areas before end of CHMI (28 days after CHMI)
- Use of systemic antibiotics with known antimalarial activity within 30 days of study enrollment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones, or azithromycin)
- Receipt of an investigational product in the 30 days preceding enrollment, or planned receipt during the study period
- Prior receipt of a malaria vaccine
- Immunization with more than three other vaccines within the past four weeks
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- HIV infection
- Any confirmed or suspected immunosuppressive or immunodeficient state, asplenia, recurrent, severe infections and 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 enrolment
- Known or suspected hemolytic disease or presence of hemoglobinopathies
- Pregnancy, lactation or intention to become pregnant during the study
- Contraindications to the use of the following antimalarial medications: atovaquoneproguanil, artemether-lumefantrine or mefloquine
- History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
- History of serious psychiatric condition that may affect participation in the study (including but not restricted to organic, including symptomatic, mental disorders [ICD-10 code: F00-F09], schizophrenia, schizotypal and delusional disorders [F20-F29], mood (affective) disorders [F30-F39], mental retardation [F70-F79], Disorders of psychological development [F80-F89] or any other psychiatric condition that required hospitalization or psychiatric treatment over an extended period).
- Any other serious chronic illness requiring hospital specialist supervision
- Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 60 g (men) or 40 g (women) per day or a carbohydrate deficient transferrin (CDT) level ≥2.5%
- Suspected or known injecting drug abuse in the 5 years preceding enrollment
- Positive for hepatitis B surface antigen (HBs-antigen)
- Seropositive for hepatitis C virus (antibodies to HCV)
- Falling in moderate risk or higher categories for fatal or non-fatal cardiovascular event within 5 years (>10%) determined by non-invasive criteria for cardiac risk
- Abnormal electrocardiogram on screening: pathologic Q wave and significant ST-T wave changes, left ventricular hypertrophy, clinically significant arrhythmias, left bundle branch block, secondary or tertiary A-V heart block
- A QT/QTcB interval >450 ms
- Volunteers unable to be closely followed for social, geographic or psychological reasons
- Any clinically significant abnormal finding on biochemistry or hematology blood tests, urine analysis or clinical examination
- History of seizure (except isolated and uncomplicated febrile convulsion at childhood)
- Any other significant disease, disorder or finding which, in the opinion of the investigator, may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data
Trial locations and contacts
1 site in 1 country.
Germany1 site
Institute of Tropical Medicine, University of Tuebingen, Wilhelmstr. 27
Tübingen, D-72074
About this study
Official title: Sequential Optimization of Dose and Schedule of PfSPZ Vaccine, Verified by Randomized, Controlled, Double-blind Immunization and Controlled Human Malaria Infection in Malaria-naïve, Healthy Adult Volunteers in Germany
MAVACHE is a sequential dose and schedule optimization trial of intravenous immunization with PfSPZ Vaccine in 18 to 54 malaria-naïve, healthy adult volunteers receiving 9x10^5, 1.35x10^6, or 2.7x10^6 PfSPZ per dose and a total dose between 2.7x10^6 and 8.1x10^6 PfSPZ followed by CHMI with 3,200 fully infectious PfSPZ (PfSPZ Challenge).
PfSPZ Challenge (7G8) to assess vaccine efficacy, safety, tolerability and infectivity of ascending PfSPZ doses will be assessed in healthy, malaria-naïve volunteers.
Read the detailed description
The study is to take place at Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen Germany.
The study has two phases: 1) dose optimization, and 2) regimen verification. In the first phase groups A, B1, B2, C1, C2 and C3 will be vaccinated sequentially in a pre-specified order, followed by homologous CHMI with 3,200 PfSPZ Challenge (NF54) three weeks after last vaccine injection.
Dose optimization phase A: 9x10^5 PfSPZ on Days 0, 7 and 28 (n = 6) B1: 1.35x10^6 PfSPZ on Days 0 and 7 (n = 6) B2: 1.35x10^6 PfSPZ on Days 0, 7, and 28 (n = 6) C1: 2.7x10^6 PfSPZ on Day 0 (n = 6) C2: 2.7x10^6 PfSPZ on Day 0 and 7 (n = 6) C3: 2.7x10^6 PfSPZ on Days 0, 7 and 28 (n = 6)
In parallel to CHMI with PfSPZ Challenge (NF54) during the optimization phase, a total of nine volunteers will receive either 800, 1,600 or 3,200 PfSPZ Challenge (7G8) (PfSPZ Challenge (7G8) dose finding) to assess safety, tolerability and infectivity of PfSPZ Challenge (7G8) in malaria-naïve healthy adult volunteers.
PfSPZ Challenge (7G8) dose finding/infection D1: 800 PfSPZ (n = 3) D2: 1,600 PfSPZ (n = 3) D3: 3,200 PfSPZ (n = 3)
Subsequently, the shortest efficacious regimen (V1) and a three-dose regimen (Day 0, 7 and 28) of the highest safe dose (V2) will be selected and verified against placebo (normal saline (NS)). Groups V1 and V2 will be vaccinated at approximately the same time and undergo repeat CHMI three and eight weeks after the last immunization. Volunteers will either receive PfSPZ Vaccine or NS as placebo. Allocation will be random and double blind. Repeat CHMI will be done with PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8), given in a randomized sequence. All immunizations are given by direct venous inoculation (DVI).
Regimen verification phase V1: Shortest efficacious regimen (n = 12) against placebo (n = 6) V2: Maximum regimen (n = 12) against placebo (n = 6) P1: Placebo for V1 group (n=6) P2 Placebo for V2 group (n=6)
- Conditions
- Malaria
- Being tested
- PfSPZ Vaccine, PfSPZ Challenge (NF54), PfSPZ Challenge (7G8), Normal saline
- Keywords
- Plasmodium falciparum, PfSPZ Vaccine, PfSPZ Challenge (NF54), PfSPZ Challenge (7G8), CHMI
- Medical subject headings
- Malaria, Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PfSPZ VaccineBiological
Aseptic, purified, vialed, cryopreserved, radiation-attenuated, Plasmodium falciparum sporozoites, strain NF54
PfSPZ Challenge (NF54)Biological
Live, infectious, aseptic, purified, vialed, cryopreserved, Plasmodium falciparum sporozoites, strain NF54
PfSPZ Challenge (7G8)Biological
Live, infectious, aseptic, purified, vialed, cryopreserved, Plasmodium falciparum sporozoites, strain 7G8
Normal salineOther
0.9% sodium chloride
| Study group | Role | What they receive |
|---|---|---|
| Optimization Phase - Group A | Experimental | n=6; three times 9x10^5 PfSPZ Vaccine on Days 0, 7 and 28 by DVI. Group A will undergo homologous CHMI with 3,200 PfSPZ Challenge (NF54), 3 weeks after the last dose of vaccine.
If >75% efficacious, the treatment will be simplified to two times 1.35x10^6 PfSPZ Vaccine on Days 0 and 7 (Group B1).
If <75% efficacious, the treatment will be increased to three times 1.35x10^6 PfSPZ Vaccine on Days 0, 7 and 28 (Group B2) Receives: Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (NF54) |
| Optimization Phase - Group B1 | Experimental | n=6; two times 1.35x10^6 PfSPZ Vaccine on Days 0 and 7 by DVI. Group B1 will undergo homologous CHMI with 3,200 PfSPZ Challenge (NF54), 3 weeks after the last dose of vaccine.
If >75% efficacious, the treatment will be simplified to one injection 2.7x10^6 PfSPZ Vaccine (Group C1).
If <75% efficacious, the treatment will be increased to two times 2.7x10^6 PfSPZ Vaccine on Days 0 and 7 (Group C2). Receives: Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (NF54) |
| Optimization Phase - Group B2 | Experimental | n=6; three times 1.35x10^6 PfSPZ Vaccine on Days 0, 7 and 28 by DVI. Group B2 will undergo homologous CHMI with 3,200 PfSPZ Challenge (NF54), 3 weeks after the last dose of vaccine.
If >75% efficacious, the treatment will be simplified to two times 2.7x10^6 PfSPZ Vaccine on Days 0 and 7 (Group C2).
If <75% efficacious, the treatment will be increased to three times 2.7x10^6 PfSPZ Vaccine on Days 0, 7 and 28 (Group C3). Receives: Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (NF54) |
| Optimization Phase - Group C1 | Experimental | n=6; one time 2.7x10^6 PfSPZ Vaccine by DVI. Group C1 will undergo homologous CHMI with 3,200 PfSPZ Challenge (NF54), 3 weeks after vaccination.
If Group C1 gets vaccinated, study will proceed to verification phase after completion. Receives: Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (NF54) |
| Optimization Phase - Group C2 | Experimental | n=6; two times 2.7x10^6 PfSPZ Vaccine by DVI. Group C2 will undergo homologous CHMI with 3,200 PfSPZ Challenge (NF54), 3 weeks after vaccination.
If Group C2 gets vaccinated, study will proceed to verification phase after completion. Receives: Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (NF54) |
| Optimization Phase - Group C3 | Experimental | n=6; three times 2.7x10^6 PfSPZ Vaccine by DVI. Group C3 will undergo homologous CHMI with 3,200 PfSPZ Challenge (NF54), 3 weeks after vaccination.
In case C3 shows <75% efficacy, verification phase will not be done. Receives: Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (NF54) |
| PfSPZ Challenge (7G8) dose finding - Group D1 | Experimental | n=3, one dose of 800 PfSPZ Challenge (7G8) by DVI.
This is a dose finding study to assess safety, tolerability and infectivity of PfSPZ Challenge (7G8) administered DVI. CHMI with PfSPZ Challenge (7G8) will be done approximately at the same time as homologous CHMI to assess efficacy of immunization with PfSPZ Vaccine in the dose optimization phase. All volunteers receiving CHMI will be monitored by thick blood smear microscopy and qPCR until Day 28 or antimalarial treatment. Receives: Biological: PfSPZ Challenge (7G8) |
| PfSPZ Challenge (7G8) dose finding - Group D2 | Experimental | n=3, one dose of 1,600 PfSPZ Challenge (7G8) by DVI.
This is a dose finding study to assess safety, tolerability and infectivity of PfSPZ Challenge (7G8) administered DVI. CHMI with PfSPZ Challenge (7G8) will be done approximately at the same time as homologous CHMI to assess efficacy of immunization with PfSPZ Vaccine in the dose optimization phase. All volunteers receiving CHMI will be monitored by thick blood smear microscopy and qPCR until Day 28 or antimalarial treatment. Receives: Biological: PfSPZ Challenge (7G8) |
| PfSPZ Challenge (7G8) dose finding - Group D3 | Experimental | n=3, one dose of 3,200 PfSPZ Challenge (7G8) by DVI.
This is a dose finding study to assess safety, tolerability and infectivity of PfSPZ Challenge (7G8) administered DVI. CHMI with PfSPZ Challenge (7G8) will be done approximately at the same time as homologous CHMI to assess efficacy of immunization with PfSPZ Vaccine in the dose optimization phase. All volunteers receiving CHMI will be monitored by thick blood smear microscopy and qPCR until Day 28 or antimalarial treatment. Receives: Biological: PfSPZ Challenge (7G8) |
| Verification Phase - Group V1 | Experimental | n=12; optimal regimen from phase 1 - shortest, well tolerated safe schedule that provides >75% protection (5/6) against homologous CHMI (V1).
Optimal \& maximum regimens will be compared in this phase. The maximum regimen is a 3-dose regimen (Day 0, 7, 28) with highest well-tolerated PfSPZ Vaccine dose/injection (V2).
Efficacy will be determined by repeat CHMI 3 and 8 weeks after last immunization. Inoculation of 2 CHMIs will be done about 35 days (5 weeks) apart.
CHMI with PfSPZ Challenge (NF54) and CHMI with PfSPZ Challenge (7G8) will be administered in one of 2 sequences (NF54-7G8 or 7G8-NF54). Allocation to the 2 sequences will be double blind, random, at a 1:1 ratio and nested within the intervention groups (V1 and V2 PfSPZ Vaccine and placebo (P1 and P2)). CHMI will be done at a dose of 3,200 PfSPZ unless the dose escalation study of PfSPZ Challenge (7G8) indicates that a different dose would be preferable for 7G8. Receives: Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (NF54); Biological: PfSPZ Challenge (7G8) |
| Verification Phase - Group V2 | Experimental | n=12; maximum regimen from the phase 1 - 3-dose regimen (Day 0, 7 and 28) with highest well-tolerated PfSPZ Vaccine dose per injection (V2).
Optimal \& maximum regimens will be compared in this phase. The optimal regimen (shortest, well tolerated and safe schedule) that provides >75% protection (5/6) against homologous CHMI (V1).
In case that shortest efficacious regimen during phase 1 is C3, 12 volunteers will be vaccinated and 6 volunteers will receive NS during this phase. In this case optimal regimen equals maximum regimen (3 x 2.7x10^6 PfSPZ). Group V2/P2 will not be immunized.
Efficacy will be determined by repeat CHMI 3 and 8 weeks after last immunization. Inoculation of 2 CHMIs will be done about 35 days (5 weeks) apart.
CHMI with PfSPZ Challenge (NF54) and CHMI with PfSPZ Challenge (7G8) will be administered as described in Group V1. Receives: Biological: PfSPZ Vaccine; Biological: PfSPZ Challenge (NF54); Biological: PfSPZ Challenge (7G8) |
| Verification Phase - Group P1 | Placebo comparator | n=6; normal saline as placebo. This group will follow the regimen selected for Group V1.
Efficacy of the vaccination regimen will be determined by CHMI which will be done by repeat CHMI three and eight weeks after the last immunization. Inoculation of the two CHMIs will be done approximately 35 days (5 weeks) apart.
CHMI with PfSPZ Challenge (NF54) and CHMI with PfSPZ Challenge (7G8) will be administered as described in Group V1. Receives: Biological: PfSPZ Challenge (NF54); Biological: PfSPZ Challenge (7G8); Other: Normal saline |
| Verification Phase - Group P2 | Placebo comparator | n=6; NS as placebo. This group will follow the regimen selected for Group V2.
In case that shortest efficacious regimen during phase 1 is C3, 12 volunteers will be vaccinated and 6 volunteers will receive NS during this phase. In this case optimal regimen equals maximum regimen (3 x 2.7x10^6 PfSPZ). Group V2/P2 will not be immunized.
Efficacy will be determined by repeat CHMI 3 and 8 weeks after the last immunization. Inoculation of the 2 CHMIs will be done about 35 days (5 weeks) apart.
CHMI with PfSPZ Challenge (NF54) and CHMI with PfSPZ Challenge (7G8) will be administered as described in Group V1. Receives: Biological: PfSPZ Challenge (NF54); Biological: PfSPZ Challenge (7G8); Other: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number or occurrence of at least possibly related Grade 3 AEs and serious adverse events (SAEs) for PfSPZ Vaccine
Number or occurrence of at least possibly related Grade 3 AEs and SAEs from time of first administration of PfSPZ Vaccine to the end of the follow-up period.
Measured: Around 14 months (from day of first immunization through study completion)
PfSPZ Challenge (7G8) dose finding - Number or occurrence of at least possibly related Grade 3 AEs and SAEs
Number or occurrence of at least possibly related Grade 3 AEs and SAEs from time of first administration of PfSPZ Challenge (7G8) to the end of the follow-up period.
Measured: Around 140 days (from day of first PfSPZ Challenge (7G8) CHMI through end of follow-up)
Secondary outcomes (3)
Number of adverse events following immunization (AEFI) for PfSPZ Vaccine
Number of adverse events following immunization (AEFI) from time of first administration of PfSPZ Vaccine to first administration of PfSPZ Challenge for CHMI consistent with a causal relationship.
Measured: About 7 weeks (from day of first vaccination until 3 weeks after last vaccination)
Proportion of volunteers who become parasitemic will be recorded, detected by thick blood film microscopy or qPCR
Thick blood film microscopy and quantitative polymerase chain reaction (qPCR) assays will be performed during CHMI follow-up. The proportion of volunteers who become parasitemic will be recorded, detected by thick blood film microscopy or qPCR, within 28 days following CHMI with 3,200 PfSPZ, given either as a single dose of 3,200 PfSPZ Challenge (NF54) (optimization phase) or as two subsequent injections of 3,200 PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8), respectively in the verification phase.
Measured: Up to 4 weeks (from day of CHMI until 28 days)
Proportion of volunteers who do not become parasitemic (protected) against homologous (NF54) and heterologous (7G8) CHMI, respectively.
This endpoint can only be assessed during the verification phase of the trial.
Measured: About 28 days (from day of first CHMI till 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2016 (estimated)
- Study start29 Aug 2016
- Primary completion19 Oct 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanaria Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Institute of Tropical Medicine, University of Tuebingen, German Federal Ministry of Education and Research, German Center for Infection Research
- Responsible party
- Sponsor
- Investigators
- Benjamin Mordmüller, MD, Principal investigator, Institute of Tropical Medicine, University of Tuebingen, Wilhelmstr. 27, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02704533
- Sponsor's protocol ID
- MAVACHE
- Other IDs
- 2015-005123-11, 2015
- Status last verified
- Jan 2019
- First submitted
- 1 Mar 2016
- Last updated
- 1 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Wichers-Misterek JS, Krumkamp R, Held J, von Thien H, Wittmann I, Hoppner YD, Ruge JM, Moser K, Dara A, Strauss J, Esen M, Fendel R, Sulyok Z, Jeninga MD, Kremsner PG, Sim BKL, Hoffman SL, Duffy MF, Otto TD, Gilberger TW, Silva JC, Mordmuller B, Petter M, Bachmann A. The exception that proves the rule: Virulence gene expression at the onset of Plasmodium falciparum blood stage infections. PLoS Pathog. 2023 Jun 29;19(6):e1011468. doi: 10.1371/journal.ppat.1011468. eCollection 2023 Jun.
PubMed 37384799Mordmuller B, Sulyok Z, Sulyok M, Molnar Z, Lalremruata A, Calle CL, Bayon PG, Esen M, Gmeiner M, Held J, Heimann HL, Woldearegai TG, Ibanez J, Flugge J, Fendel R, Kreidenweiss A, Kc N, Murshedkar T, Chakravarty S, Riyahi P, Billingsley PF, Church LWP, Richie TL, Sim BKL, Hoffman SL, Kremsner PG. A PfSPZ vaccine immunization regimen equally protective against homologous and heterologous controlled human malaria infection. NPJ Vaccines. 2022 Aug 23;7(1):100. doi: 10.1038/s41541-022-00510-z.
PubMed 35999221
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sequential Optimization of Dose and Schedule of PfSPZ Vaccine, Verified by Randomized, Controlled, Double-blind Immunization and Controlled Human Malaria Infection in Malaria-naïve, Healthy Adult Volunteers in Germany
- ClinicalTrials.gov ID
- NCT02704533
- Acronym / sponsor ID
- MAVACHE
- Conditions
- Malaria
- Keywords
- Plasmodium falciparum, PfSPZ Vaccine, PfSPZ Challenge (NF54), PfSPZ Challenge (7G8), CHMI
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Sanaria Inc.Industry (pharma, biotech, devices)
- Collaborators
- Institute of Tropical Medicine, University of Tuebingen, German Federal Ministry of Education and Research, German Center for Infection Research
- Study start
- 29 Aug 2016 (actual)
- Primary completion
- 19 Oct 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 10 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
MAVACHE is a sequential dose and schedule optimization trial of intravenous immunization with PfSPZ Vaccine in 18 to 54 malaria-naïve, healthy adult volunteers receiving 9x10^5, 1.35x10^6, or 2.7x10^6 PfSPZ per dose and a total dose between 2.7x10^6 and 8.1x10^6 PfSPZ followed by CHMI with 3,200 fully infectious PfSPZ (PfSPZ Challenge).
PfSPZ Challenge (7G8) to assess vaccine efficacy, safety, tolerability and infectivity of ascending PfSPZ doses will be assessed in healthy, malaria-naïve volunteers.
Detailed description
The study is to take place at Institut für Tropenmedizin, Eberhard Karls Universität Tübingen, Tübingen Germany.
The study has two phases: 1) dose optimization, and 2) regimen verification. In the first phase groups A, B1, B2, C1, C2 and C3 will be vaccinated sequentially in a pre-specified order, followed by homologous CHMI with 3,200 PfSPZ Challenge (NF54) three weeks after last vaccine injection.
Dose optimization phase A: 9x10^5 PfSPZ on Days 0, 7 and 28 (n = 6) B1: 1.35x10^6 PfSPZ on Days 0 and 7 (n = 6) B2: 1.35x10^6 PfSPZ on Days 0, 7, and 28 (n = 6) C1: 2.7x10^6 PfSPZ on Day 0 (n = 6) C2: 2.7x10^6 PfSPZ on Day 0 and 7 (n = 6) C3: 2.7x10^6 PfSPZ on Days 0, 7 and 28 (n = 6)
In parallel to CHMI with PfSPZ Challenge (NF54) during the optimization phase, a total of nine volunteers will receive either 800, 1,600 or 3,200 PfSPZ Challenge (7G8) (PfSPZ Challenge (7G8) dose finding) to assess safety, tolerability and infectivity of PfSPZ Challenge (7G8) in malaria-naïve healthy adult volunteers.
PfSPZ Challenge (7G8) dose finding/infection D1: 800 PfSPZ (n = 3) D2: 1,600 PfSPZ (n = 3) D3: 3,200 PfSPZ (n = 3)
Subsequently, the shortest efficacious regimen (V1) and a three-dose regimen (Day 0, 7 and 28) of the highest safe dose (V2) will be selected and verified against placebo (normal saline (NS)). Groups V1 and V2 will be vaccinated at approximately the same time and undergo repeat CHMI three and eight weeks after the last immunization. Volunteers will either receive PfSPZ Vaccine or NS as placebo. Allocation will be random and double blind. Repeat CHMI will be done with PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8), given in a randomized sequence. All immunizations are given by direct venous inoculation (DVI).
Regimen verification phase V1: Shortest efficacious regimen (n = 12) against placebo (n = 6) V2: Maximum regimen (n = 12) against placebo (n = 6) P1: Placebo for V1 group (n=6) P2 Placebo for V2 group (n=6)
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 13
| Arm | Type | Receives |
|---|---|---|
| Optimization Phase - Group A | Experimental | Biological: PfSPZ Vaccine, Biological: PfSPZ Challenge (NF54)n=6; three times 9x10^5 PfSPZ Vaccine on Days 0, 7 and 28 by DVI. Group A will undergo homologous CHMI with 3,200 PfSPZ Challenge (NF54), 3 weeks after the last dose of vaccine. If >75% efficacious, the treatment will be simplified to two times 1.35x10^6 PfSPZ Vaccine on Days 0 and 7 (Group B1). If <75% efficacious, the treatment will be increased to three times 1.35x10^6 PfSPZ Vaccine on Days 0, 7 and 28 (Group B2) |
| Optimization Phase - Group B1 | Experimental | Biological: PfSPZ Vaccine, Biological: PfSPZ Challenge (NF54)n=6; two times 1.35x10^6 PfSPZ Vaccine on Days 0 and 7 by DVI. Group B1 will undergo homologous CHMI with 3,200 PfSPZ Challenge (NF54), 3 weeks after the last dose of vaccine. If >75% efficacious, the treatment will be simplified to one injection 2.7x10^6 PfSPZ Vaccine (Group C1). If <75% efficacious, the treatment will be increased to two times 2.7x10^6 PfSPZ Vaccine on Days 0 and 7 (Group C2). |
| Optimization Phase - Group B2 | Experimental | Biological: PfSPZ Vaccine, Biological: PfSPZ Challenge (NF54)n=6; three times 1.35x10^6 PfSPZ Vaccine on Days 0, 7 and 28 by DVI. Group B2 will undergo homologous CHMI with 3,200 PfSPZ Challenge (NF54), 3 weeks after the last dose of vaccine. If >75% efficacious, the treatment will be simplified to two times 2.7x10^6 PfSPZ Vaccine on Days 0 and 7 (Group C2). If <75% efficacious, the treatment will be increased to three times 2.7x10^6 PfSPZ Vaccine on Days 0, 7 and 28 (Group C3). |
| Optimization Phase - Group C1 | Experimental | Biological: PfSPZ Vaccine, Biological: PfSPZ Challenge (NF54)n=6; one time 2.7x10^6 PfSPZ Vaccine by DVI. Group C1 will undergo homologous CHMI with 3,200 PfSPZ Challenge (NF54), 3 weeks after vaccination. If Group C1 gets vaccinated, study will proceed to verification phase after completion. |
| Optimization Phase - Group C2 | Experimental | Biological: PfSPZ Vaccine, Biological: PfSPZ Challenge (NF54)n=6; two times 2.7x10^6 PfSPZ Vaccine by DVI. Group C2 will undergo homologous CHMI with 3,200 PfSPZ Challenge (NF54), 3 weeks after vaccination. If Group C2 gets vaccinated, study will proceed to verification phase after completion. |
| Optimization Phase - Group C3 | Experimental | Biological: PfSPZ Vaccine, Biological: PfSPZ Challenge (NF54)n=6; three times 2.7x10^6 PfSPZ Vaccine by DVI. Group C3 will undergo homologous CHMI with 3,200 PfSPZ Challenge (NF54), 3 weeks after vaccination. In case C3 shows <75% efficacy, verification phase will not be done. |
| PfSPZ Challenge (7G8) dose finding - Group D1 | Experimental | Biological: PfSPZ Challenge (7G8)n=3, one dose of 800 PfSPZ Challenge (7G8) by DVI. This is a dose finding study to assess safety, tolerability and infectivity of PfSPZ Challenge (7G8) administered DVI. CHMI with PfSPZ Challenge (7G8) will be done approximately at the same time as homologous CHMI to assess efficacy of immunization with PfSPZ Vaccine in the dose optimization phase. All volunteers receiving CHMI will be monitored by thick blood smear microscopy and qPCR until Day 28 or antimalarial treatment. |
| PfSPZ Challenge (7G8) dose finding - Group D2 | Experimental | Biological: PfSPZ Challenge (7G8)n=3, one dose of 1,600 PfSPZ Challenge (7G8) by DVI. This is a dose finding study to assess safety, tolerability and infectivity of PfSPZ Challenge (7G8) administered DVI. CHMI with PfSPZ Challenge (7G8) will be done approximately at the same time as homologous CHMI to assess efficacy of immunization with PfSPZ Vaccine in the dose optimization phase. All volunteers receiving CHMI will be monitored by thick blood smear microscopy and qPCR until Day 28 or antimalarial treatment. |
| PfSPZ Challenge (7G8) dose finding - Group D3 | Experimental | Biological: PfSPZ Challenge (7G8)n=3, one dose of 3,200 PfSPZ Challenge (7G8) by DVI. This is a dose finding study to assess safety, tolerability and infectivity of PfSPZ Challenge (7G8) administered DVI. CHMI with PfSPZ Challenge (7G8) will be done approximately at the same time as homologous CHMI to assess efficacy of immunization with PfSPZ Vaccine in the dose optimization phase. All volunteers receiving CHMI will be monitored by thick blood smear microscopy and qPCR until Day 28 or antimalarial treatment. |
| Verification Phase - Group V1 | Experimental | Biological: PfSPZ Vaccine, Biological: PfSPZ Challenge (NF54), Biological: PfSPZ Challenge (7G8)n=12; optimal regimen from phase 1 - shortest, well tolerated safe schedule that provides >75% protection (5/6) against homologous CHMI (V1). Optimal \& maximum regimens will be compared in this phase. The maximum regimen is a 3-dose regimen (Day 0, 7, 28) with highest well-tolerated PfSPZ Vaccine dose/injection (V2). Efficacy will be determined by repeat CHMI 3 and 8 weeks after last immunization. Inoculation of 2 CHMIs will be done about 35 days (5 weeks) apart. CHMI with PfSPZ Challenge (NF54) and CHMI with PfSPZ Challenge (7G8) will be administered in one of 2 sequences (NF54-7G8 or 7G8-NF54). Allocation to the 2 sequences will be double blind, random, at a 1:1 ratio and nested within the intervention groups (V1 and V2 PfSPZ Vaccine and placebo (P1 and P2)). CHMI will be done at a dose of 3,200 PfSPZ unless the dose escalation study of PfSPZ Challenge (7G8) indicates that a different dose would be preferable for 7G8. |
| Verification Phase - Group V2 | Experimental | Biological: PfSPZ Vaccine, Biological: PfSPZ Challenge (NF54), Biological: PfSPZ Challenge (7G8)n=12; maximum regimen from the phase 1 - 3-dose regimen (Day 0, 7 and 28) with highest well-tolerated PfSPZ Vaccine dose per injection (V2). Optimal \& maximum regimens will be compared in this phase. The optimal regimen (shortest, well tolerated and safe schedule) that provides >75% protection (5/6) against homologous CHMI (V1). In case that shortest efficacious regimen during phase 1 is C3, 12 volunteers will be vaccinated and 6 volunteers will receive NS during this phase. In this case optimal regimen equals maximum regimen (3 x 2.7x10^6 PfSPZ). Group V2/P2 will not be immunized. Efficacy will be determined by repeat CHMI 3 and 8 weeks after last immunization. Inoculation of 2 CHMIs will be done about 35 days (5 weeks) apart. CHMI with PfSPZ Challenge (NF54) and CHMI with PfSPZ Challenge (7G8) will be administered as described in Group V1. |
| Verification Phase - Group P1 | Placebo comparator | Biological: PfSPZ Challenge (NF54), Biological: PfSPZ Challenge (7G8), Other: Normal salinen=6; normal saline as placebo. This group will follow the regimen selected for Group V1. Efficacy of the vaccination regimen will be determined by CHMI which will be done by repeat CHMI three and eight weeks after the last immunization. Inoculation of the two CHMIs will be done approximately 35 days (5 weeks) apart. CHMI with PfSPZ Challenge (NF54) and CHMI with PfSPZ Challenge (7G8) will be administered as described in Group V1. |
| Verification Phase - Group P2 | Placebo comparator | Biological: PfSPZ Challenge (NF54), Biological: PfSPZ Challenge (7G8), Other: Normal salinen=6; NS as placebo. This group will follow the regimen selected for Group V2. In case that shortest efficacious regimen during phase 1 is C3, 12 volunteers will be vaccinated and 6 volunteers will receive NS during this phase. In this case optimal regimen equals maximum regimen (3 x 2.7x10^6 PfSPZ). Group V2/P2 will not be immunized. Efficacy will be determined by repeat CHMI 3 and 8 weeks after the last immunization. Inoculation of the 2 CHMIs will be done about 35 days (5 weeks) apart. CHMI with PfSPZ Challenge (NF54) and CHMI with PfSPZ Challenge (7G8) will be administered as described in Group V1. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- Healthy adults aged 18 to 45 years
- 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 ('Hausarzt' in German) if required
- Residence in Tübingen or surroundings for the period of the trial
- Women only: Must agree to practice continuous effective contraception for the duration of the study (a method which results in a failure rate less than 1% per year)
Key exclusion criteria (26 listed)
- History of P. falciparum malaria
- Planned travel to malaria endemic areas before end of CHMI (28 days after CHMI)
- Use of systemic antibiotics with known antimalarial activity within 30 days of study enrollment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones, or azithromycin)
- Receipt of an investigational product in the 30 days preceding enrollment, or planned receipt during the study period
- Prior receipt of a malaria vaccine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PfSPZ VaccineAseptic, purified, vialed, cryopreserved, radiation-attenuated, Plasmodium falciparum sporozoites, strain NF54 | Biological | Optimization Phase - Group A, Optimization Phase - Group B1, Optimization Phase - Group B2, Optimization Phase - Group C1, Optimization Phase - Group C2, Optimization Phase - Group C3, Verification Phase - Group V1, Verification Phase - Group V2 |
| PfSPZ Challenge (NF54)Live, infectious, aseptic, purified, vialed, cryopreserved, Plasmodium falciparum sporozoites, strain NF54 | Biological | Optimization Phase - Group A, Optimization Phase - Group B1, Optimization Phase - Group B2, Optimization Phase - Group C1, Optimization Phase - Group C2, Optimization Phase - Group C3, Verification Phase - Group P1, Verification Phase - Group P2, Verification Phase - Group V1, Verification Phase - Group V2 |
| PfSPZ Challenge (7G8)Live, infectious, aseptic, purified, vialed, cryopreserved, Plasmodium falciparum sporozoites, strain 7G8 | Biological | PfSPZ Challenge (7G8) dose finding - Group D1, PfSPZ Challenge (7G8) dose finding - Group D2, PfSPZ Challenge (7G8) dose finding - Group D3, Verification Phase - Group P1, Verification Phase - Group P2, Verification Phase - Group V1, Verification Phase - Group V2 |
| Normal saline0.9% sodium chloride | Other | Verification Phase - Group P1, Verification Phase - Group P2 |
Primary outcome
Number or occurrence of at least possibly related Grade 3 AEs and serious adverse events (SAEs) for PfSPZ Vaccine
Time frame: Around 14 months (from day of first immunization through study completion)
Number or occurrence of at least possibly related Grade 3 AEs and SAEs from time of first administration of PfSPZ Vaccine to the end of the follow-up period.
PfSPZ Challenge (7G8) dose finding - Number or occurrence of at least possibly related Grade 3 AEs and SAEs
Time frame: Around 140 days (from day of first PfSPZ Challenge (7G8) CHMI through end of follow-up)
Number or occurrence of at least possibly related Grade 3 AEs and SAEs from time of first administration of PfSPZ Challenge (7G8) to the end of the follow-up period.
3 secondary outcomes
Number of adverse events following immunization (AEFI) for PfSPZ Vaccine
Time frame: About 7 weeks (from day of first vaccination until 3 weeks after last vaccination)
Proportion of volunteers who become parasitemic will be recorded, detected by thick blood film microscopy or qPCR
Time frame: Up to 4 weeks (from day of CHMI until 28 days)
Proportion of volunteers who do not become parasitemic (protected) against homologous (NF54) and heterologous (7G8) CHMI, respectively.
Time frame: About 28 days (from day of first CHMI till 28 days)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Feb 2019.
- Derived from this study: PubMed 37384799Wichers-Misterek JS, Krumkamp R, Held J, von Thien H, Wittmann I, Hoppner YD, Ruge JM, Moser K, Dara A, Strauss J, Esen M, Fendel R, Sulyok Z, Jeninga MD, Kremsner PG, Sim BKL, Hoffman SL, Duffy MF, Otto TD, Gilberger TW, Silva JC, Mordmuller B, Petter M, Bachmann A. The exception that proves the rule: Virulence gene expression at the onset of Plasmodium falciparum blood stage infections. PLoS Pathog. 2023 Jun 29;19(6):e1011468. doi: 10.1371/journal.ppat.1011468. eCollection 2023 Jun.
- Derived from this study: PubMed 35999221Mordmuller B, Sulyok Z, Sulyok M, Molnar Z, Lalremruata A, Calle CL, Bayon PG, Esen M, Gmeiner M, Held J, Heimann HL, Woldearegai TG, Ibanez J, Flugge J, Fendel R, Kreidenweiss A, Kc N, Murshedkar T, Chakravarty S, Riyahi P, Billingsley PF, Church LWP, Richie TL, Sim BKL, Hoffman SL, Kremsner PG. A PfSPZ vaccine immunization regimen equally protective against homologous and heterologous controlled human malaria infection. NPJ Vaccines. 2022 Aug 23;7(1):100. doi: 10.1038/s41541-022-00510-z.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benjamin Mordmüller, MD principal investigator
Institute of Tropical Medicine, University of Tuebingen, Wilhelmstr. 27, Germany
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PfSPZ Vaccine, PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8) in people with Malaria, run by Sanaria Inc. at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number or occurrence of at least possibly related Grade 3 AEs and serious adverse events (SAEs) for PfSPZ Vaccine (time frame: Around 14 months (from day of first immunization through study completion)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02704533, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Feb 2019.