A Challenge Study to Assess the Blood-stage Efficacy of Full-length SUM-101 Malaria Vaccine Candidate

NCT07124156 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: EVI-CT-002
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of the study is to test the efficacy using a homologous CHMI of this vaccine candidate early in the development path in a population living in malaria-endemic areas. In the previous Phase Ia and Ib trials, no efficacy endpoints were defined, and therefore there is currently no data on the SUM-101 vaccine efficacy. The proposed clinical trial will enrol malaria pre-exposed healthy adults and will be the second trial where the IMP will be administered to healthy adult participants in Tanzania with some pre-existing immunity against malaria. The vaccination part of this study will be performed in a randomised, double-blinded, controlled design to evaluate the safety, reactogenicity and immunogenicity of the candidate malaria vaccine SUM-101 (MSP1 with GLA-SE as adjuvant). Given that SUM-101 is a malaria vaccine with an important blood-stage component, we propose to use CHMI with the 3D7 P. falciparum strain-infected red blood cells to establish initial vaccine efficacy data after the third vaccination in a malaria-exposed population.

Conditions

Malaria Fever

Keywords

SUM-01; CHMI; Malaria

Outcome Measures

Primary Outcomes (6)

• Efficacy- Time to diagnosis

  Blood-stage efficacy of the SUM-101 vaccine against 3D7 clone parasites in a CHMI model in healthy malaria-exposed adult volunteers, measured as time to diagnosis in the vaccine arm compared to controls. Time to diagnosis is defined as the number of days from challenge to treatment

  From Day 84 to Day 168

• Frequency of local and systemic solicited adverse events

  Safety of SUM-101 vaccine in healthy malaria-exposed adults as assessed by the frequency of local and systemic solicited adverse events (AEs)

  After each vaccination (done on Day 0, Day 28 and Day 56) up to 7 days post-vaccination

• Frequency of local and systemic unsolicited adverse events

  Safety of SUM-101 vaccine in healthy malaria-exposed adults as assessed by the frequency of local and systemic unsolicited adverse events

  After each vaccination (done on Day 0, Day 28 and Day 56) up to 28 days post-vaccination

• Frequency of any serious adverse events (SAE)

  Safety of SUM-101 vaccine in healthy malaria-exposed adults as assessed by any serious adverse events (SAE)

  Baseline (Day 0 before 1st vaccination) to end of the follow up (Day 168)

• Number of participants with treatment-related adverse events as assessed by safety laboratory measures of haematology and biochemistry.

  Number of participants with treatment-related adverse events as assessed by safety laboratory measures of haematology and biochemistry. Changes in laboratory safety parameters as summarised as absolute values of: Haematology: Haemoglobin, WBC (differentiation of eosinophils and neutrophils), platelets and haematocrit. Biochemistry: parameters at screening will include: ALT, AST, total bilirubin, creatinine and glucose (random). Troponin sample will be collected before 1st vaccination (at baseline) and stored to be run retrospectively if needed in case of a cardiac event. The sample collected at the time of the cardiac event will be compared with the sample collected at baseline. Urinalysis performed by dipstick. Proteinuria, glucose and blood.

  Baseline (Day 0 before 1st vaccination) to end of the follow up (Day 168)

• MSP1-specific IgG antibody levels assessed by ELISA

  Humoral immunogenicity of SUM-101 in malaria-exposed adults assessed as MSP1-specific IgG antibody levels measured by serum ELISA in sera collected at Day 0 (pre-vaccination) and Day 84 (Pre-CHMI).

  Day 0 (pre-vaccination) and Day 84 (Pre-CHMI).

Secondary Outcomes (4)

• Immunogenicity to MSP1-specific IgM antibody levels measured by ELISA

  Day 0 (pre-vaccination) and Day 84 (Pre-CHMI).

• Immunogenicity assessed as antibody-mediated complement fixation activity.

  Day 0 (pre-vaccination) and Day 84 (Pre-CHMI)

• Antibody-mediated complement fixation activity

  Day 0 (pre-vaccination) and Day 84 (Pre-CHMI)

• Antibody-dependent respiratory burst (ADRB) activity

  Day 0 (pre-vaccination) and Day 84 (Pre-CHMI)

Other Outcomes (1)

• Comparison of P. falciparum in vivo parasite growth rates

  Day 84 to Day 168

Study Arms (2)

Three dose SUM-101

EXPERIMENTAL

Twelve participants will receive three monthly inoculations (on D0, D28 and D56) with the IMP, SUM-101.

Biological: SUM-101; Other: CHMI

Three dose Verorab

ACTIVE COMPARATOR

12 participants will receive three monthly inoculations (on D0, D28 and D56) with the IMP Verorab®

Other: CHMI; Biological: Verorab®

Interventions

SUM-101 BIOLOGICAL

Once randomised to either the SUM-101 or the rabies control vaccine, the participant will always receive the same dose of the same compound (150 µg MSP1 protein dissolved in 0.9% NaCl with 250 µl (5µg) of adjuvant GLA-SE and there are no dose adjustments foreseen. The three vaccine doses will be applied in 4-week intervals on day 0, day 28 and day 56.

Three dose SUM-101

CHMI OTHER

Experimental intervention: The participants will receive a target dose of 2,800 viable intraerythrocytic P. falciparum 3D7 parasites, in a volume of 2 mL injectable saline. The erythrocytes will be thawed, resuspended and viability will be calculated. The total erythrocyte number will be between \~3.9×106 and \~5.2×108 (average: \~4.55×108) per dose with ≥80% (\~3.64×108) P. falciparum ring-stage parasites and around 34% (\~1.24×108) viability. This number of viable P. falciparum ring-stage parasites will be diluted to establish 2800 per syringe that will be administered. Challenge dose will be administered to all volunteers as an intravenous injection at the clinical site following instructions in an established SOP. The parasites injected in each volunteer will be quantified retrospectively using qPCR analysis. The parasites injected in each volunteer will be quantified retrospectively using qPCR analysis. No dose adjustments are foreseen. As described in the protocol

Three dose SUM-101; Three dose Verorab

Verorab® BIOLOGICAL

Once randomised the participant will receive the or Verorab® and there are no dose adjustments foreseen. The three vaccine doses will be applied in 4-week intervals on day 0, day 28 and day 56.

Three dose Verorab

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Written informed consent obtained before any study procedure.
• Literate participants aged ≥18 - ≤45 years of African origin.
• Female and male participants willing to practice effective contraception from 4 weeks before 1st vaccination (female participants only) and up to 12 weeks after the last vaccination or CHMI (female and male participants)
• Female participants must be willing to undergo multiple serum pregnancy tests.
• Available to participate in follow-up for the duration of the study, including the CHMI in-patient confinement period.
• Contactable by phone during the whole study period.
• At least two years of residence in the Bagamoyo district or nearby districts in the 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.
• Confirmation of understanding of design, procedures, risks and benefits of the study by scoring 10 out of 10 in a structured ten questions with a maximum of two attempts.
• General good health based on assessment of medical history and clinical examination.
• The volunteer agrees to refrain from blood donation for 12 months following CHMI.
• Volunteer agrees to refrain from intensive physical exercise (disproportionate to the volunteer's usual daily activity or exercise routine) during the malaria challenge period.

You may not qualify if:

• 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.
• High anti-schizont antibody level as measured by ELISA at screening.
• 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 are 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 8 weeks after the 3rd vaccination.
• Any history, or evidence at screening, of clinically significant symptoms, physical signs or laboratory values suggestive of systemic disorders, including renal, hepatic, cardiovascular, pulmonary, skin, immunodeficiency, neurological, psychiatric, allergy, endocrine, malignant, haematological, infectious disease, epilepsy 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, Hepatitis B (HBV) or Hepatitis C (HCV) tests. (The testing will only be requested on the discretion of clinician)

Sponsors & Collaborators

• European Vaccine Initiative: lead
• Luxembourg Institute of Health: collaborator
• Ifakara Health Institute: collaborator

MeSH Terms

Conditions

Malaria

Interventions

1-acetyl-1,2,3,3a,8,8a-hexahydro-8a-hydroxy-5-methoxypyrrolo(2,3-b)indole

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Ally Olotu, MD

  Ifakara Health Institute (IHI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Souyet Chang Rodríguez, PhD/MSc

CONTACT

+436705546575; souyet.chang-rodriguez@euvaccine.eu

Irene Nkumama, PhD

CONTACT

+491787823620; Irene.Nkumama@euvaccine.eu

Study Design

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

Study Record Dates

• First Submitted: July 4, 2025
• First Posted: August 15, 2025
• Study Start: March 20, 2026
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: November 21, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share