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Assessment of the Malaria Vaccine Candidate SumayaVac-1 in Healthy Adults Aged 18-45 Years Living in a Malaria Endemic Country (SUM-101)

Primary Purpose

Malaria

Status
Recruiting
Phase
Phase 1
Locations
Tanzania
Study Type
Interventional
Intervention
SumayaVac-1(SUM-101)
Verorab
CHMI
Sponsored by
Swiss Tropical & Public Health Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Malaria focused on measuring Plasmodium falciparum, Controlled Human Malaria Infection, Tanzania, Phase Ib, Vaccine

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Written informed consent obtained before any study procedure. Literate participants aged 18-45 years of African origin. Female and male participants practicing contraception from 4 weeks before 1st immunization and up to 12 weeks after the last immunization or CHMI. Available to participate in follow-up for the duration of the study. Contactable by phone during the whole study period. At least two years residence in the Bagamoyo district or nearby districts in Coastal and Dar-es-Salaam regions and planning to reside there for at least 9 more months. Agreement to provide personal contact information and contact information of another household member or close friend. Female participants must be willing to avoid pregnancy if selected for participation in the trial and to undergo multiple serum pregnancy testing. Confirmation of understanding of design, procedures, risk and benefits of the study in a test with maximum of two attempts. General good health based on assessment of medical history and clinical examination. Exclusion Criteria: Previous participation in any malaria vaccine trial in the last 3 years. Participation in any other clinical trial involving investigational medicinal products within 30 days prior to the screening assessment. Previous history of drug or alcohol abuse interfering with normal social function within one year prior to enrolment. Previous vaccination with a rabies vaccine. Intake of chronic medication, especially immunosuppressive agents (steroids, immunomodulating drugs) during the 13 weeks preceding the screening visit or during the study period. Known hypersensitivity to any of the vaccine components (adjuvant or protein) or anti-malarial treatments. Body mass index (BMI) of <18 or >30 Kg/m2. Participants unable to be closely followed for social, geographic or psychological reasons. Any vaccination from 4 weeks prior to the 1st vaccination and (none planned) up to 6 weeks after the 3rd vaccination or CHMI. Symptoms, physical signs or laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the trial results or compromise the health of the participants. 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 (atrio-ventricular) heart block. Any clinically significant laboratory values at screening outside of normal ranges for study participants. Malaria positivity at screening (microscopy or qPCR positive). Positive HIV, HBV or HCV tests. For females: Positive pregnancy test or actively breast feeding.

Sites / Locations

  • Ifakara Health InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

SumayaVac-1(SUM-101)

Verorab

Arm Description

Candidate malaria Vaccine (Investigational Medicinal Product (IMP)). 20 participants will be randomised to receive three monthly inoculations of the IMP

Comparator used as a control. 20 participants will be randomised to receive three monthly inoculations of the comparator.

Outcomes

Primary Outcome Measures

Local and systemic adverse events (AEs) at least possibly related to the IMP after vaccination
Local and systemic solicited adverse events (AEs) at least possibly related to the investigational medicinal product (IMP) recorded after each vaccination (done on Day 0, Day 28 and Day 56 up to 7 days later to evaluate safety and reactogenicity of SumayaVac-1 (SUM-101)
Local and systemic unsolicited reactogenicity after vaccination
Local and systemic unsolicited reactogenicity recorded after each vaccination (done on Day 0, Day 28 and Day 56 up to 28 days later to evaluate the safety and reactogenicity of SumayaVac-1 (SUM-101)
Any serious adverse events (SAE) occurring after the 1st vaccination until the participant's last visit
Any serious adverse events (SAE) occurring after the 1st vaccination until the participant's last visit to evaluate the safety and reactogenicity of SumayaVac-1 (SUM-101)
Changes in laboratory safety parameters between baseline and 28 days after vaccination
Changes in laboratory safety parameters as defined in the protocol for every participant between baseline (Day 0 before 1st vaccination) to 28 days after each of the vaccinations to evaluate the safety and reactogenicity of SumayaVac-1 (SUM-101)
Changes in laboratory safety parameter prior to vaccination to 28 days after that vaccination
Changes in laboratory safety parameters as defined in the protocol for every participant between values recorded just prior to each vaccination (on Day 0, Day 28 and Day 56) and values found 28 days after proceeding with vaccination to evaluate the safety and reactogenicity of SumayaVac-1 (SUM-101)
Longevity of antibody responses to SumayaVac-1 (SUM-101) by ELISA
Longevity of antibody responses to SumayaVac-1 (SUM-101) by ELISA for all participants at Day 0 pre-vaccination, Day 28 (Week 4), Day 56 (Week 8), Day 84 (Week 12), Day 112 (Week 16), Day 140 (Week 20), and additionally at Day 168 (Week 24) and Day 252 (Week 36) for participants that undergo homologous CHMI, to evaluate the humoral immunogenicity
Fold change of antibody responses to SumayaVac-1 (SUM-101) in comparison to baseline
Fold change of antibody responses to SumayaVac-1 (SUM-101) in comparison to baseline (Day 0 pre-vaccination) for all participants to Day 28 (Week 4), Day 56 (Week 8), Day 84 (Week 12), Day 112 (Week 16), Day 140 (Week 20), and additionally at Day 168 (Week 24) and Day 252 (Week 36) for participants that undergo homologous CHMI, to evaluate the humoral immunogenicity

Secondary Outcome Measures

Evaluation of the opsonic phagocytosis activity of vaccine induced antibodies
In vitro immunological assay to evaluate humoral immune responses by measuring opsonic phagocytosis activity in the sera or blood of all participants, at Day 0 pre-vaccination, Day 28 (Week 4), Day 56 (Week 8), Day 84 (Week 12), Day 112 (Week 16), Day 140 (Week 20), and additionally at Day 168 (Week 24) and Day 252 (Week 36) for participants that undergo homologous CHMI
Evaluation of complement fixation, activation and/or membrane attack complex (MAC) formation of vaccine-induced antibodies
In vitro immunological assay to evaluate humoral immune responses by assessing complement fixation, activation and/or membrane attack complex (MAC) formation in the sera or blood of all participants, at Day 0 pre-vaccination, Day 28 (Week 4), Day 56 (Week 8), Day 84 (Week 12), Day 112 (Week 16), Day 140 (Week 20), and additionally at Day 168 (Week 24) and Day 252 (Week 36) for participants that undergo homologous CHMI
Evaluation of antibody-dependent respiratory burst (ADRB) activity of vaccine-induced antibodies
In vitro lab immunological assay to evaluate immune responses by assessing antibody-dependent respiratory burst (ADRB) activity measured in the sera or blood of all participants, at Day 0 pre-vaccination, Day 28 (Week 4), Day 56 (Week 8), Day 84 (Week 12), Day 112 (Week 16), Day 140 (Week 20), and additionally at Day 168 (Week 24) and Day 252 (Week 36) for participants that undergo homologous CHMI
Evaluation of antibody-dependent cellular cytotoxicity (ADCC-NK cells) activity of vaccine-induced antibodies
In vitro immunological assay to evaluate humoral immune responses by assessing antibody-dependent cellular cytotoxicity (ADCC-NK cells) activity in the sera or blood of all participants, at Day 0 pre-vaccination, Day 28 (Week 4), Day 56 (Week 8), Day 84 (Week 12), Day 112 (Week 16), Day 140 (Week 20), and additionally at Day 168 (Week 24) and Day 252 (Week 36) for participants that undergo homologous CHMI
Evaluation of immune-mediated growth inhibition activity on Plasmodium falciparum asexual blood stage cell lines
In vitro functional assay to evaluate immune-mediated growth inhibition activity on a panel of Plasmodium falciparum asexual blood stage cell lines measured in the sera or blood of all participants, at Day 0 pre-vaccination, Day 28 (Week 4), Day 56 (Week 8), Day 84 (Week 12), Day 112 (Week 16), Day 140 (Week 20), and additionally at Day 168 (Week 24) and Day 252 (Week 36) for participants that undergo homologous CHMI
Development of P.falciparum asexual blood stage parasitemia (pre-patent period, parasite multiplication rate (PMR) and percentage of parasite negative participants in SumayaVac-1 (SUM-101) versus Verorab® arm) measured by thick blood smear (TBS)
Development of P. falciparum asexual blood stage parasitemia (pre-patent period, parasite multiplication rate (PMR) and percentage of parasite negative participants in SumayaVac-1 (SUM-101) versus Verorab® arm) measured by thick blood smear (TBS) in venous blood of all participants that undergo homologous CHMI
Development of P. falciparum asexual blood parasitemia (pre-patent period, PMR and percentage of parasite negative participants in SumayaVac-1 (SUM-101) versus Verorab® arm) by qPCR
Development of P. falciparum parasitemia (pre-patent period, parasite multiplication rate (PMR) and percentage of parasite negative participants in SumayaVac-1 (SUM-101) versus Verorab® arm) measured by qPCR in the venous blood for all participants that undergo homologous CHMI
Cellular immune responses to SumayaVac-1 (SUM-101)
Immune assays to assess changes in immune cell populations in response to SumayaVac-1 (SUM-101) by (i) CD4+ and CD8+ ELISpot assays, (ii) SumayaVac-1 (SUM-101) specific cells characterised by flow cytometry-based immunophenotyping using intracellular cytokine staining (ICS), (iii) functional gene expression analysis, and/or other assays to be defined measured in all participants
Comparison of MSP-1 IgG antibody concentrations by ELISA
Comparison of MSP-1 IgG antibody concentrations by ELISA between malaria pre-exposed participants in the current study and historical data obtained from malaria naïve participants of previous Phase Ia study conducted in Heidelberg that are assessed among SumayaVac-1 (SUM-101) participants only

Full Information

First Posted
October 27, 2022
Last Updated
August 30, 2023
Sponsor
Swiss Tropical & Public Health Institute
Collaborators
Ifakara Health Institute, Sumaya Biotech GmbH & Co. KG
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1. Study Identification

Unique Protocol Identification Number
NCT05644067
Brief Title
Assessment of the Malaria Vaccine Candidate SumayaVac-1 in Healthy Adults Aged 18-45 Years Living in a Malaria Endemic Country
Acronym
SUM-101
Official Title
A Randomised, Controlled, Double-blind, Parallel Group, Single Center Phase Ib Trial to Assess Safety, Reactogenicity, Immunogenicity and Parasite Growth Rates After Controlled Human Malaria Infection of a Candidate Dual-stage Malaria Vaccine, SumayaVac-1 (MSP-1 With GLA-SE as Adjuvant) in Healthy Malaria Exposed Adults of African Origin Aged 18-45 Years
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
August 25, 2023 (Actual)
Primary Completion Date
July 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Swiss Tropical & Public Health Institute
Collaborators
Ifakara Health Institute, Sumaya Biotech GmbH & Co. KG

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Malaria remains a major infectious disease causing a heavy burden of mortality and morbidity in populations living in tropical and subtropical regions. Large, international research efforts have been invested into the development of anti-malaria vaccination strategies, however, currently there is only one malaria vaccine approved for use in the pediatric population, which provides a moderate and short-lived protection. Therefore, there is a need to develop a malaria vaccine that will be essential to further strengthen malaria control measures in future. A Phase Ia trial with the same IMP (SumayaVac-1 vaccine developed using a full-length recombinant MSP-1 administered along with the adjuvant GLA-SE) in Caucasians in Heidelberg, Germany, proved to be well tolerated and safe. However, a Phase Ib clinical trial on healthy participants residing in a malaria endemic country would be essential to evaluate the safety and reactogenicity in the target population. The project aims to investigate the safety, reactogenicity, immunogenicity of the candidate malaria vaccine, SumayaVac-1 (SUM-101) in 40 healthy participants (men and women) of African origin in Bagamoyo, Tanzania. It will also employ the Controlled Human Malaria Infection model to evaluate the ability of this vaccine candidate to induce immune responses that prevent malaria parasites from getting into the red blood cells thereby preventing development of malaria.
Detailed Description
Objectives: To evaluate in healthy adults of African origin previously exposed to the malaria parasite receiving SumayaVac-1 (SUM-101) versus rabies control (Verorab®) vaccine: Primary Objectives Safety and reactogenicity of SumayaVac-1 (SUM-101). Immunogenicity of SumayaVac-1 (SUM-101). Secondary Objectives • The relationship of SumayaVac-1 (SUM-101) vaccine-induced antibody levels, in vitro effector functions and isotype distribution with asexual blood stage parasite growth rates after homologous controlled human malaria infection (CHMI). Exploratory Objectives Comparison of SumayaVac-1 (SUM-101) induced immunoglobulin isotype distribution and duration between malaria pre-exposed and malaria naïve participants from the previous Phase Ia study in Heidelberg. Fine scale epitope mapping of SumayaVac-1 (SUM-101) specific antibodies, including specific CD4+ and CD8+ T-cell epitopes using peptide arrays, to investigate the association between cellular immune response with humoral seroconversion and investigate the potential association with protection after homologous CHMI. Comparison of SumayaVac-1 (SUM-101) induced cellular immunity between malaria pre-exposed and malaria naïve participants from the previous Phase Ia study in Heidelberg. Investigation of the B- and T-Cell repertoire before and after SumayaVac-1 (SUM-101) vaccination, as well as after homologous CHMI. Integrated transcriptome and immunoglobulin gene repertoire analyses of MSP-1 specific B-cells using single-cell technologies. Glycosylation patterns of MSP-1 specific functional antibodies. Investigate off-target IgG and IgM repertoire after SumayaVac-1 (SUM-101) vaccination using immunoproteomics and their association with protection after homologous CHMI. Investigate the structure of MSP-1 protein bound to functional antibodies by cryo-electron tomography to map conformational epitopes. Mechanisms of malaria specific antibody diversity generation, post-translational modification of antibodies, and B- and T-cell memory generation and maintenance. Human and parasite transcriptome in peripheral blood during early stage asexual blood stage parasitemia after homologous CHMI. The quality and quantity of peripheral blood γδ T-cell responses in participants with or without homologous CHMI (all 40 participants). Liver to blood inoculum size of the CHMI-induced parasites after homologous CHMI (25 participants that undergo homologous CHMI). Study Design: This is a randomised, controlled, double-blind, parallel group, single center Phase Ib trial to assess the safety, reactogenicity, and immunogenicity and parasite growth rates after homologous CHMI of SumayaVac-1 (SUM-101) in healthy, malaria-exposed adults of African origin aged 18-45 years. The study is divided in two parts: Vaccinations (Part 1) In total, 40 participants will be enrolled (male and female). 20 participants will be randomised to receive three monthly inoculations (on D0, D28 and D56) with the investigational product, SumayaVac-1 (SUM-101), and 20 participants will be randomised to receive the registered rabies vaccine, Verorab®, as controls. For operational reasons the participants will be split in two groups of 20 participants. Group 1 will have a sentinel subgroup (2 SumayaVac-1 (SUM-101) & 1 Verorab® rabies vaccine) with a 48 hours safety surveillance period before the remaining 17 participants (8 SumayaVac-1 (SUM-101) & 9 Verorab® rabies vaccine) of the group 1 receive their 1st vaccination. Group 2 will be composed of 20 participants (10 SumayaVac-1 (SUM-101) & 10 Verorab® rabies vaccine). All visits in group 2 will be shifted by 3 weeks compared to group 1 to create minimal overlap of study-related activities. After each vaccination (done on D0, D28 and D56), the participants will remain at the facility for 2 hours prior to their discharge for home. The participant will be called daily by phone (or home visits if required) until 6 days post vaccination for follow-up. For all participants, vaccination follow-up visits at the site will occur at 7, 14 and 28 days after each vaccination. CHMI (Part 2) In total, 25 participants (15 SumayaVac-1 (SUM-101) & 10 Verorab® vaccinated, selected randomly from the overall 40 participants) will undergo homologous CHMI with attenuated sporozoites 4 weeks after the 3rd vaccination. For operational reasons, the participants will remain in the two separate groups defined in the vaccination part. After the CHMI, the participant will stay for 2 hours at the facility before being discharged. The participant will be called daily by phone (or home visits if required) until 4 days post CHMI for follow-up. 5 days after CHMI, participants will return to the site and be admitted to the ward for closer observation during the period when parasitemia could possibly be detected. The participant will remain in confinement at the site until he/she is considered positive for malaria or reaches 28 days post CHMI. All participants will then receive anti-malarial treatment (for 3 days) and be discharged after being confirmed to be malaria negative. CHMI follow-up visits at the site will take place at 3 months (D168) and 6 months (D252) post CHMI. Measurements and Procedures: Written informed consent will be taken prior to any study procedure. Healthy participants will be screened and randomised before administration of the study IMP. Vaccinations (Part 1) On the day of the 1st vaccination, the health status of the participant is re-checked and eligibility confirmed. Samples for safety, humoral, cellular and exploratory measurements are taken (baseline). Vaccination is administered and the participant remains at site for 2 hours before being discharged. Telephone follow-ups (or home visits if required) will be performed daily until 6 days after each vaccination. On 7, 14 and 28 days after each vaccination (done on D0, D28 and D56), the participant will be invited to come back to the facility and health status is checked. Further participant follow-up visits will take place at D112 (W16) and D140 (W20) post 1st vaccination. Sampling for humoral and cellular responses will be performed at D112 (W16) and D140 (W20). Additionally, sampling for exploratory measurements will be performed at D112 (W16) (Vac1 + 4 month follow-up site visit). CHMI (Part 2) 4 weeks after the 3rd vaccination, a randomly selected subset of participants (n=25; 15 SumayaVac-1 (SUM-101) & 10 Verorab® vaccinated) are invited to participate in the CHMI part of the study. On the day of the CHMI, the health status of the participant is checked and eligibility confirmed. Samples for safety, cellular, humoral and exploratory measurements are taken. CHMI is performed and the participants remain at site for 2 hours before being discharged. Telephone follow-ups (or home visits if required) will be performed daily until 4 days post CHMI to check participant's health status. 5 days post CHMI, participants will return to the site to check the health status and for admission to the ward for closer observation. During this confinement period at the site, clinical assessments and blood withdrawals will be performed until the participant is considered malaria positive (count of >500 parasites/µl in the qPCR or malaria symptoms with a positive rapid diagnostic test (RDT)) or reaches 28 days post CHMI. Blood samples will be stored for qPCR based assessment of asexual blood stage parasitemia and PMR. Once considered positive for malaria or at 28 days post CHMI (if still malaria negative), samples for exploratory measurements will be taken followed by anti-malarial treatment for 3 days. At the end of the anti-malarial treatment, the health status will be checked and blood samples will be collected to confirm asexual blood stage negativity. When there is no medical contraindication, the participant will be discharged. CHMI follow-up visits will take place at 3 months (D168) and 6 months (D252) post CHMI and will include health checks and sampling for humoral responses. Number of Participants with Rationale: Vaccination: 40 adult participants Overall: 20 SumayaVac-1 (SUM-101) and 20 Verorab® control Group 1 Sentinel sub-group 2 SumayaVac-1 (SUM-101) 1 Verorab® control Follower Group 8 SumayaVac-1 (SUM-101) 9 Verorab® control Group 2 10 SumayaVac-1 (SUM-101) 10 Verorab® control CHMI: 25 from 40 adult participants who received vaccination Overall: 15 SumayaVac-1 (SUM-101) and 10 Verorab® control Group 1 12 (7 having received SumayaVac-1 (SUM-101) & 5 having received Verorab® control) Group 2 13 (8 having received SumayaVac-1 (SUM-101) & 5 having received Verorab® control) As this is a Phase I trial, no formal sample size calculation has been done. The sample size is considered sufficient to examine the safety and reactogenicity of SumayaVac-1 (SUM-101), and humoral and cellular immunogenicity. Study Product / Intervention: Vaccination: Intra-muscular injection of SumayaVac-1 (SUM-101) composed of 150 µg MSP-1 + 5 μg GLA-SE CHMI: Direct venous inoculation of 3.2 x 103 purified, infectious P. falciparum sporozoites (PfSPZ Challenge (NF54 strain), Sanaria®) Control Intervention: Vaccination control: Intra-muscular injection of rabies vaccine (Verorab®) Study Duration: The total study duration including screening will be approximately 40 weeks including the screening period. The study duration for each participant involved in the vaccinations (Part 1) and the CHMI (Part 2) (n=25) is 36 weeks. For participants not undergoing CHMI (n=15) the study duration will be 20 weeks. Study Centre: Bagamoyo Research and Training Center of the Ifakara Health Institute Statistical Analysis incl. Power Analysis: See above for sample size justification. To evaluate the safety and reactogenicity primary endpoints, AEs and SAEs will be presented according to the endpoint definitions above. AE reporting will include verbatim term, preferred term (PT), system organ class (SOC), treatment, severity, relationship to the interventional products, and seriousness, reporting numbers of participants experiencing each event and total numbers of each event. Laboratory safety parameters will be summarized as absolute values and changes at 28 days after each vaccination compared to baseline (before 1st vaccination) and compared to values just prior to each vaccination. To evaluate the immunogenicity primary endpoints as defined above, SumayaVac-1 (SUM-101) vaccine induced humoral immunogenicity will be summarized as antibody responses to SumayaVac-1 (SUM-101) by ELISA over time, and fold changes of antibody responses relative to baseline. For all analyses, data will be listed for each participant. Descriptive analyses will be performed (number of observations, arithmetic or geometric mean, standard deviation, minimum, maximum, median, interquartile range, as appropriate, for continuous data, and counts and percentages for categorical data). Results will be presented by vaccination received, overall and separately for participants who were/were not in the CHMI part. Further details will be elaborated in a Statistical Analysis Plan (SAP), including for the secondary and exploratory objectives.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
Keywords
Plasmodium falciparum, Controlled Human Malaria Infection, Tanzania, Phase Ib, Vaccine

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
A randomised, controlled, double-blind, parallel group, single center Phase Ib trial to assess safety, reactogenicity, immunogenicity of a candidate dual-stage malaria vaccine, SumayaVac-1 (MSP-1 with GLA-SE as adjuvant) in healthy participants aged 18-45 years. The study will also employ the Controlled Human Malaria Infection model to evaluate the ability of the vaccine candidate to induce immune responses that prevent malaria parasites from getting into the red blood cells thereby preventing development of malaria.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
This trial will be conducted in a double-blinded manner. Namely, the participants, site staff, sponsor staff, the study monitor(s) and the trial statistician will be blinded to the treatment allocation. The independent statistician and the pharmacist are not blind throughout the study.
Allocation
Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SumayaVac-1(SUM-101)
Arm Type
Experimental
Arm Description
Candidate malaria Vaccine (Investigational Medicinal Product (IMP)). 20 participants will be randomised to receive three monthly inoculations of the IMP
Arm Title
Verorab
Arm Type
Placebo Comparator
Arm Description
Comparator used as a control. 20 participants will be randomised to receive three monthly inoculations of the comparator.
Intervention Type
Biological
Intervention Name(s)
SumayaVac-1(SUM-101)
Intervention Description
One immunization every 4 weeks for 3 months (total 3 immunizations)
Intervention Type
Biological
Intervention Name(s)
Verorab
Intervention Description
One immunization every 4 weeks for 3 months (total 3 immunizations)
Intervention Type
Biological
Intervention Name(s)
CHMI
Other Intervention Name(s)
PfSPZ
Intervention Description
Controlled Human Malaria Infection (CHMI)- challenge with Plasmodium falciparum sporozoites in a sub-group of participants who received SumayaVac-1(SUM-101) or Verorab
Primary Outcome Measure Information:
Title
Local and systemic adverse events (AEs) at least possibly related to the IMP after vaccination
Description
Local and systemic solicited adverse events (AEs) at least possibly related to the investigational medicinal product (IMP) recorded after each vaccination (done on Day 0, Day 28 and Day 56 up to 7 days later to evaluate safety and reactogenicity of SumayaVac-1 (SUM-101)
Time Frame
Recorded up to 7 days after each vaccination
Title
Local and systemic unsolicited reactogenicity after vaccination
Description
Local and systemic unsolicited reactogenicity recorded after each vaccination (done on Day 0, Day 28 and Day 56 up to 28 days later to evaluate the safety and reactogenicity of SumayaVac-1 (SUM-101)
Time Frame
Recorded up to 28 days after each vaccination
Title
Any serious adverse events (SAE) occurring after the 1st vaccination until the participant's last visit
Description
Any serious adverse events (SAE) occurring after the 1st vaccination until the participant's last visit to evaluate the safety and reactogenicity of SumayaVac-1 (SUM-101)
Time Frame
Recorded from after 1st vaccination (Day 0 post-vaccination) until the participant's last visit (Day 252)
Title
Changes in laboratory safety parameters between baseline and 28 days after vaccination
Description
Changes in laboratory safety parameters as defined in the protocol for every participant between baseline (Day 0 before 1st vaccination) to 28 days after each of the vaccinations to evaluate the safety and reactogenicity of SumayaVac-1 (SUM-101)
Time Frame
Changes recorded between baseline (Day 0 before 1st vaccination) to 28 days after each vaccination
Title
Changes in laboratory safety parameter prior to vaccination to 28 days after that vaccination
Description
Changes in laboratory safety parameters as defined in the protocol for every participant between values recorded just prior to each vaccination (on Day 0, Day 28 and Day 56) and values found 28 days after proceeding with vaccination to evaluate the safety and reactogenicity of SumayaVac-1 (SUM-101)
Time Frame
Changes prior to each vaccination to 28 days after proceeding with vaccination
Title
Longevity of antibody responses to SumayaVac-1 (SUM-101) by ELISA
Description
Longevity of antibody responses to SumayaVac-1 (SUM-101) by ELISA for all participants at Day 0 pre-vaccination, Day 28 (Week 4), Day 56 (Week 8), Day 84 (Week 12), Day 112 (Week 16), Day 140 (Week 20), and additionally at Day 168 (Week 24) and Day 252 (Week 36) for participants that undergo homologous CHMI, to evaluate the humoral immunogenicity
Time Frame
Titres assessed between Day 0 (pre-vaccination) up to Day 252 (last follow up visit)
Title
Fold change of antibody responses to SumayaVac-1 (SUM-101) in comparison to baseline
Description
Fold change of antibody responses to SumayaVac-1 (SUM-101) in comparison to baseline (Day 0 pre-vaccination) for all participants to Day 28 (Week 4), Day 56 (Week 8), Day 84 (Week 12), Day 112 (Week 16), Day 140 (Week 20), and additionally at Day 168 (Week 24) and Day 252 (Week 36) for participants that undergo homologous CHMI, to evaluate the humoral immunogenicity
Time Frame
Fold changes assessed between Day 0 (pre-vaccination) up to Day 252 (last follow up visit)
Secondary Outcome Measure Information:
Title
Evaluation of the opsonic phagocytosis activity of vaccine induced antibodies
Description
In vitro immunological assay to evaluate humoral immune responses by measuring opsonic phagocytosis activity in the sera or blood of all participants, at Day 0 pre-vaccination, Day 28 (Week 4), Day 56 (Week 8), Day 84 (Week 12), Day 112 (Week 16), Day 140 (Week 20), and additionally at Day 168 (Week 24) and Day 252 (Week 36) for participants that undergo homologous CHMI
Time Frame
Changes assessed between Day 0 (pre-vaccination) up to Day 252 (last follow up visit)
Title
Evaluation of complement fixation, activation and/or membrane attack complex (MAC) formation of vaccine-induced antibodies
Description
In vitro immunological assay to evaluate humoral immune responses by assessing complement fixation, activation and/or membrane attack complex (MAC) formation in the sera or blood of all participants, at Day 0 pre-vaccination, Day 28 (Week 4), Day 56 (Week 8), Day 84 (Week 12), Day 112 (Week 16), Day 140 (Week 20), and additionally at Day 168 (Week 24) and Day 252 (Week 36) for participants that undergo homologous CHMI
Time Frame
Changes assessed between Day 0 (pre-vaccination) up to Day 252 (last follow up visit)
Title
Evaluation of antibody-dependent respiratory burst (ADRB) activity of vaccine-induced antibodies
Description
In vitro lab immunological assay to evaluate immune responses by assessing antibody-dependent respiratory burst (ADRB) activity measured in the sera or blood of all participants, at Day 0 pre-vaccination, Day 28 (Week 4), Day 56 (Week 8), Day 84 (Week 12), Day 112 (Week 16), Day 140 (Week 20), and additionally at Day 168 (Week 24) and Day 252 (Week 36) for participants that undergo homologous CHMI
Time Frame
Changes assessed between Day 0 (pre-vaccination) up to Day 252 (last follow up visit)
Title
Evaluation of antibody-dependent cellular cytotoxicity (ADCC-NK cells) activity of vaccine-induced antibodies
Description
In vitro immunological assay to evaluate humoral immune responses by assessing antibody-dependent cellular cytotoxicity (ADCC-NK cells) activity in the sera or blood of all participants, at Day 0 pre-vaccination, Day 28 (Week 4), Day 56 (Week 8), Day 84 (Week 12), Day 112 (Week 16), Day 140 (Week 20), and additionally at Day 168 (Week 24) and Day 252 (Week 36) for participants that undergo homologous CHMI
Time Frame
Changes assessed between Day 0 (pre-vaccination) up to Day 252 (last follow up visit)
Title
Evaluation of immune-mediated growth inhibition activity on Plasmodium falciparum asexual blood stage cell lines
Description
In vitro functional assay to evaluate immune-mediated growth inhibition activity on a panel of Plasmodium falciparum asexual blood stage cell lines measured in the sera or blood of all participants, at Day 0 pre-vaccination, Day 28 (Week 4), Day 56 (Week 8), Day 84 (Week 12), Day 112 (Week 16), Day 140 (Week 20), and additionally at Day 168 (Week 24) and Day 252 (Week 36) for participants that undergo homologous CHMI
Time Frame
Changes assessed between Day 0 (pre-vaccination) up to Day 252 (last follow up visit)
Title
Development of P.falciparum asexual blood stage parasitemia (pre-patent period, parasite multiplication rate (PMR) and percentage of parasite negative participants in SumayaVac-1 (SUM-101) versus Verorab® arm) measured by thick blood smear (TBS)
Description
Development of P. falciparum asexual blood stage parasitemia (pre-patent period, parasite multiplication rate (PMR) and percentage of parasite negative participants in SumayaVac-1 (SUM-101) versus Verorab® arm) measured by thick blood smear (TBS) in venous blood of all participants that undergo homologous CHMI
Time Frame
Changes between Day 84-Day 112
Title
Development of P. falciparum asexual blood parasitemia (pre-patent period, PMR and percentage of parasite negative participants in SumayaVac-1 (SUM-101) versus Verorab® arm) by qPCR
Description
Development of P. falciparum parasitemia (pre-patent period, parasite multiplication rate (PMR) and percentage of parasite negative participants in SumayaVac-1 (SUM-101) versus Verorab® arm) measured by qPCR in the venous blood for all participants that undergo homologous CHMI
Time Frame
Between Day 84-Day 112
Title
Cellular immune responses to SumayaVac-1 (SUM-101)
Description
Immune assays to assess changes in immune cell populations in response to SumayaVac-1 (SUM-101) by (i) CD4+ and CD8+ ELISpot assays, (ii) SumayaVac-1 (SUM-101) specific cells characterised by flow cytometry-based immunophenotyping using intracellular cytokine staining (ICS), (iii) functional gene expression analysis, and/or other assays to be defined measured in all participants
Time Frame
Changes assessed between Day 0 (pre-vaccination) up to Day 140
Title
Comparison of MSP-1 IgG antibody concentrations by ELISA
Description
Comparison of MSP-1 IgG antibody concentrations by ELISA between malaria pre-exposed participants in the current study and historical data obtained from malaria naïve participants of previous Phase Ia study conducted in Heidelberg that are assessed among SumayaVac-1 (SUM-101) participants only
Time Frame
Antibody concentrations compared between Day 0 (pre-vaccination) up to Day 84
Other Pre-specified Outcome Measures:
Title
Comparison of SumayaVac-1 (SUM-101) induced immunoglobulin isotype distribution and duration
Description
Comparison of SumayaVac-1 (SUM-101) induced immunoglobulin isotype distribution and duration in the current study and historical data obtained from malaria naïve participants of previous Phase Ia study conducted in Heidelberg that are assessed among SumayaVac-1 (SUM-101) participants only
Time Frame
Changes observed between Day 0 (pre-vaccination) up to Day 84
Title
Fine scale epitope mapping of SumayaVac-1 (SUM-101) specific antibodies
Description
Fine scale epitope mapping of SumayaVac-1 (SUM-101) specific antibodies using peptide arrays to investigate the association between humoral immunity and potential association with protection after homologous CHMI
Time Frame
Responses measured between Day 0 (pre-vaccination) up to Day 84
Title
Comparison of SumayaVac-1 (SUM-101) induced cellular immunity between malaria pre-exposed and malaria naïve participants from the previous Phase Ia study in Heidelberg
Description
Changes in immune cell populations between SumayaVac-1 (SUM-101) vaccinated malaria pre-exposed participants in the current trial and historical data from malaria naïve participants from the previous Phase Ia study conducted in Heidelberg
Time Frame
Changes measured between Day 0 (pre-vaccination) and Day 84
Title
Investigation of the B- and T-Cell repertoire
Description
Investigation of the B- and T-Cell repertoire (immune cell populations) before and after SumayaVac-1 (SUM-101) vaccination, as well as after homologous CHMI
Time Frame
Changes observed between Day 0 (pre-vaccination) up to Day 140
Title
Integrated transcriptome and immunoglobulin gene repertoire analyses
Description
Integrated transcriptome and immunoglobulin gene repertoire analyses of MSP-1 specific B-cells using single-cell technologies before and after SumayaVac-1 (SUM-101) vaccination, as well as after homologous CHMI
Time Frame
Changes observed between Day 0 (pre-vaccination) up to Day 140
Title
Glycosylation patterns of MSP-1 specific functional antibodies
Description
Lab based assays to assess the glycosylation patterns of MSP-1 specific functional antibodies
Time Frame
Changes observed between Day 0 (pre-vaccination) up to Day 84
Title
Investigate off-target IgG and IgM repertoire after SumayaVac-1 (SUM-101) vaccination
Description
Investigate off-target IgG and IgM repertoire after SumayaVac-1 (SUM-101) vaccination using immunoproteomics and their association with protection after homologous CHMI
Time Frame
Changes observed between Day 0 (pre-vaccination) up to Day 140
Title
Investigate the structure of recombinant MSP-1 protein bound to functional antibodies
Description
Investigate the structure of MSP-1 protein bound to functional antibodies by cryo-electron tomography to map conformational epitopes
Time Frame
Through study completion, an average of 1 year
Title
Measurement of asexual blood stage pre-patent period
Description
Measurement of asexual blood stage pre-patent period in participants having received SumayaVac-1 (SUM-101) versus Verorab® rabies vaccine after homologous CHMI
Time Frame
Changes observed between Day 84 - Day 112
Title
Ex vivo assessment of asexual blood stage parasite transcriptome
Description
Ex vivo assessment of asexual blood stage parasite transcriptome during homologous CHMI in participants having received SumayaVac-1 (SUM-101) versus Verorab® rabies control vaccine
Time Frame
Changes observed between Day 84- Day 112
Title
Ex vivo assessment of changes in human peripheral blood transcriptome
Description
Ex vivo assessment of changes in human peripheral blood transcriptome before, during and after homologous CHMI in participants having received SumayaVac-1 (SUM-101) versus Verorab® rabies vaccine
Time Frame
Changes observed between Day 0 (pre-vaccination) and Day 168
Title
Description of ɣδ T-cell receptor repertoire, transcriptome, functional activity and phenotypes
Description
Description of ɣδ T-cell receptor repertoire, transcriptome, functional activity and phenotypes before, during and after homologous CHMI in participants having received SumayaVac-1 (SUM-101) versus Verorab® rabies vaccine
Time Frame
Changes observed between Day 0 (pre-vaccination) and Day 168
Title
Investigate the impact of the presence of intestinal helminth infections on vaccine-induced humoral immune response
Description
Investigate the impact of the presence of intestinal helminth infections on vaccine-induced humoral immune response by comparing the quality and quantity of SumayaVac-1 (SUM-101) specific antibody isotypes between helminth infected and non-infected participants at baseline
Time Frame
Changes observed between Day 0 (pre-vaccination) and Day 84
Title
Investigate the impact of the presence of intestinal helminth infections on SumayaVac-1 (SUM-101) vaccine-induced cellular immune responses
Description
Investigate the impact of the presence of intestinal helminth infections on SumayaVac-1 (SUM-101) vaccine-induced cellular immune responses by comparing the quality and quantity of SumayaVac-1 (SUM-101) specific cytokine production and ICS results between helminth infected and non-infected participants at baseline
Time Frame
Changes observed between Day 0 (pre-vaccination) and Day 84

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Written informed consent obtained before any study procedure. Literate participants aged 18-45 years of African origin. Female and male participants practicing contraception from 4 weeks before 1st immunization and up to 12 weeks after the last immunization or CHMI. Available to participate in follow-up for the duration of the study. Contactable by phone during the whole study period. At least two years residence in the Bagamoyo district or nearby districts in Coastal and Dar-es-Salaam regions and planning to reside there for at least 9 more months. Agreement to provide personal contact information and contact information of another household member or close friend. Female participants must be willing to avoid pregnancy if selected for participation in the trial and to undergo multiple serum pregnancy testing. Confirmation of understanding of design, procedures, risk and benefits of the study in a test with maximum of two attempts. General good health based on assessment of medical history and clinical examination. Exclusion Criteria: Previous participation in any malaria vaccine trial in the last 3 years. Participation in any other clinical trial involving investigational medicinal products within 30 days prior to the screening assessment. Previous history of drug or alcohol abuse interfering with normal social function within one year prior to enrolment. Previous vaccination with a rabies vaccine. Intake of chronic medication, especially immunosuppressive agents (steroids, immunomodulating drugs) during the 13 weeks preceding the screening visit or during the study period. Known hypersensitivity to any of the vaccine components (adjuvant or protein) or anti-malarial treatments. Body mass index (BMI) of <18 or >30 Kg/m2. Participants unable to be closely followed for social, geographic or psychological reasons. Any vaccination from 4 weeks prior to the 1st vaccination and (none planned) up to 6 weeks after the 3rd vaccination or CHMI. Symptoms, physical signs or laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, psychiatric and other conditions, which could interfere with the interpretation of the trial results or compromise the health of the participants. 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 (atrio-ventricular) heart block. Any clinically significant laboratory values at screening outside of normal ranges for study participants. Malaria positivity at screening (microscopy or qPCR positive). Positive HIV, HBV or HCV tests. For females: Positive pregnancy test or actively breast feeding.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Elisabeth Reus
Phone
+41 61 284 89 66
Email
elisabeth.reus@swisstph.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Suzanne Gajewski
Phone
+41 61 284 89 62
Email
suzanne.gajewski@swisstph.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claudia Daubenberger, PhD
Organizational Affiliation
Swiss Tropical & Public Health Institute
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Ally Olotu, MD
Organizational Affiliation
Ifakara Health Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Ifakara Health Institute
City
Bagamoyo
ZIP/Postal Code
74
Country
Tanzania
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ally Olotu, MD
Phone
+255 718 927 104
Email
aolotu@ihi.or.tz

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32025341
Citation
Blank A, Furle K, Jaschke A, Mikus G, Lehmann M, Husing J, Heiss K, Giese T, Carter D, Bohnlein E, Lanzer M, Haefeli WE, Bujard H. Immunization with full-length Plasmodium falciparum merozoite surface protein 1 is safe and elicits functional cytophilic antibodies in a randomized first-in-human trial. NPJ Vaccines. 2020 Jan 31;5(1):10. doi: 10.1038/s41541-020-0160-2. eCollection 2020.
Results Reference
background
Links:
URL
https://www.nature.com/articles/s41541-020-0160-2
Description
Related Info

Learn more about this trial

Assessment of the Malaria Vaccine Candidate SumayaVac-1 in Healthy Adults Aged 18-45 Years Living in a Malaria Endemic Country

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