NCT07124156

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

A Randomised Phase Ib Trial to Assess the Blood-stage Efficacy of SUM-101 Malaria Vaccine in Adults Residing in Malaria-endemic Settings, After Controlled Human Malaria Infection Using 3D7 P. Falciparum Blood-stage Malaria Infection

• Status: Not Yet Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Sponsor: European Vaccine Initiative · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Full-length MSP1/GLA-SE (SUM-101) malaria vaccine (formerly SumayaVac-1) has been developed by Sumaya Biotech, a spin-off from Heidelberg University, Germany. SUM-101 is a vaccine based on the 3D7 strain (D-form) of full-length merozoite surface protein 1 (full-length MSP1). The full-length MSP1 is expressed as a recombinant heterodimeric protein in E. coli and lyophilised at 150 μg/vial. The lyophilised MSP1 protein is stored at 2 - 8°C. The adjuvant, GLA-SE, was developed by Access to Advanced Health Institute (AAHI), a Washington non-profit corporation with offices at 1616 Eastlake Ave. E, Suite 400, Seattle, WA 98102, USA. It is a stable oil-in-water emulsion containing a synthetic analogue of bacterial glucopyranosyl lipid A and functions as a toll-like receptor 4 agonist. A vial of the adjuvant contains 20μg of GLA-SE in a 400μl emulsion. GLA-SE adjuvant and emulsion formulations should be stored at 2 - 8°C. The vaccine (SUM-101) is prepared before administration by reconstituting the lyophilised protein in saline (aqueous 0.9% NaCl) and then combining it with the GLA-SE adjuvant. The formulated vaccine is stable at room temperature for up to 60 minutes and administered intramuscularly. A Phase I first-in-human, double-blinded, randomised trial (PMC6994672) was conducted to assess the safety and immunogenicity of SUM-101 in healthy malaria-naïve adult volunteers in Heidelberg, Germany. The trial demonstrated that SUM-101 is safe, with no serious adverse events (SAE) reported. Vaccination with SUM-101 induced MSP1 specific IgG and IgM antibodies that activated Fc-mediated effector mechanisms and were equally reactive against the vaccine variant (MSP1D/3D7) and a heterologous variant of MSP1 (MSP1F/FCB1). In addition, a Phase Ib trial was conducted in Bagamoyo, Tanzania (NCT05644067, data not yet published) where 20 healthy Tanzanian adults were vaccinated with SUM-101. Preliminary results indicate that SUM-101 is safe and well-tolerated in healthy African adults living in malaria-endemic areas, with ongoing assessments of antibody responses. Concurrently with this trial, a Phase Ib, randomised, controlled age de-escalation, dose-finding study to evaluate the safety, reactogenicity and immunogenicity of full-length MSP1/GLA-SE (SUM-101) malaria vaccine in healthy young children, and infants (NCT06618885) will be conducted in Burkina Faso. The protocol has been submitted for ethical and regulatory approval in Burkina Faso.

Conditions

• Malaria Fever

Interventions

Type	Name	Description
BIOLOGICAL	SUM-101	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.
OTHER	CHMI	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
BIOLOGICAL	Verorab®	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.

Timeline

• Start date: 2026-03-20
• Primary completion: 2026-07-31
• Completion: 2026-12-31
• First posted: 2025-08-15
• Last updated: 2025-11-21