NCT02704533

Brief 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 (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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
45

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Aug 2016

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 1, 2016

Completed
9 days until next milestone

First Posted

Study publicly available on registry

March 10, 2016

Completed
6 months until next milestone

Study Start

First participant enrolled

August 29, 2016

Completed
2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 19, 2018

Completed
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2018

Completed
Last Updated

February 1, 2019

Status Verified

January 1, 2019

Enrollment Period

2.1 years

First QC Date

March 1, 2016

Last Update Submit

January 31, 2019

Conditions

Malaria

Keywords

Plasmodium falciparumPfSPZ VaccinePfSPZ Challenge (NF54)PfSPZ Challenge (7G8)CHMI

Outcome Measures

Primary Outcomes (2)

  • 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.

    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.

    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

    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

    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.

    About 28 days (from day of first CHMI till 28 days)

Study Arms (13)

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)

Biological: PfSPZ VaccineBiological: 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).

Biological: PfSPZ VaccineBiological: 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).

Biological: PfSPZ VaccineBiological: 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.

Biological: PfSPZ VaccineBiological: 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.

Biological: PfSPZ VaccineBiological: 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.

Biological: PfSPZ VaccineBiological: 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.

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.

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.

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.

Biological: PfSPZ VaccineBiological: 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.

Biological: PfSPZ VaccineBiological: 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.

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.

Biological: PfSPZ Challenge (NF54)Biological: PfSPZ Challenge (7G8)Other: Normal saline

Interventions

PfSPZ VaccineBIOLOGICAL

Aseptic, purified, vialed, cryopreserved, radiation-attenuated, Plasmodium falciparum sporozoites, strain NF54

Optimization Phase - Group AOptimization Phase - Group B1Optimization Phase - Group B2Optimization Phase - Group C1Optimization Phase - Group C2Optimization Phase - Group C3Verification Phase - Group V1Verification Phase - Group V2
PfSPZ Challenge (NF54)BIOLOGICAL

Live, infectious, aseptic, purified, vialed, cryopreserved, Plasmodium falciparum sporozoites, strain NF54

Optimization Phase - Group AOptimization Phase - Group B1Optimization Phase - Group B2Optimization Phase - Group C1Optimization Phase - Group C2Optimization Phase - Group C3Verification Phase - Group P1Verification Phase - Group P2Verification Phase - Group V1Verification Phase - Group V2
PfSPZ Challenge (7G8)BIOLOGICAL

Live, infectious, aseptic, purified, vialed, cryopreserved, Plasmodium falciparum sporozoites, strain 7G8

PfSPZ Challenge (7G8) dose finding - Group D1PfSPZ Challenge (7G8) dose finding - Group D2PfSPZ Challenge (7G8) dose finding - Group D3Verification Phase - Group P1Verification Phase - Group P2Verification Phase - Group V1Verification Phase - Group V2
Normal salineOTHER

0.9% sodium chloride

Verification Phase - Group P1Verification Phase - Group P2

Eligibility Criteria

Age18 Years - 45 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • 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)
  • 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

You may not qualify if:

  • 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
  • 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
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Institute of Tropical Medicine, University of Tuebingen, Wilhelmstr. 27

Tübingen, D-72074, Germany

Location

Related Publications (2)

  • 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.

    PMID: 37384799DERIVED

  • Mordmuller 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.

    PMID: 35999221DERIVED

MeSH Terms

Conditions

MalariaMalaria, Falciparum

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Protozoan InfectionsParasitic DiseasesInfectionsMosquito-Borne DiseasesVector Borne Diseases

Intervention Hierarchy (Ancestors)

Crystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical Preparations

Study Officials

  • Benjamin Mordmüller, MD

    Institute of Tropical Medicine, University of Tuebingen, Wilhelmstr. 27, Germany

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 1, 2016

First Posted

March 10, 2016

Study Start

August 29, 2016

Primary Completion

October 19, 2018

Study Completion

December 1, 2018

Last Updated

February 1, 2019

Record last verified: 2019-01

Locations

DE(1)