Statens Serum Institut Initiates Phase2 Efficacy Trial for Standalone Multi-stage Malaria Vaccine Candidate 

Statens Serum Institut (SSI), today announced the initiation of a Phase 2 Clinical trial for its investigational malaria vaccine, which contains SSI’s ProC6C antigen and Novavax’s Matrix-M™ adjuvant. Developed and manufactured by SSI, under the support of the European & Developing Countries Clinical Trials Partnership (EDCTP2), this vaccine candidate was previously evaluated for safety and immunogenicity in healthy human adult volunteers in Burkina Faso and Mali. SSI will now measure the efficacy of the ability of ProC6C/Matrix-M vaccine to prevent infection through a Phase 2 challenge study conducted in adults aged 18-50 years.

• ProC6C is a multi-stage malaria vaccine designed to reduce parasite transmission and prevent human infection.
• Two Phase 1 trials of ProC6C administered with Matrix-M adjuvant demonstrated favorable safety and tolerability at all dose levels in healthy adults, as well as transmission-reducing activity
•  A Phase 2 controlled human malaria infection (CHMI) study has now been initiated to determine efficacy of preventing infection and thereby clinical malaria.

ProC6C/Matrix-M is a first-in-class multi-stage malaria vaccine aimed at eliciting both transmission reducing activity and direct personal protection, with the goal of extending both community and individual benefits. The antigen is a novel single recombinant protein targeting three malaria antigens: Pfs230, Pfs48/45 and the Circumsporozoite Protein (CSP).

The results of the first Phase 1 study conducted in Burkina Faso and recently published in the Journal of Clinical Investigation, was the first human trial evaluating a malaria vaccine comprised of the Pfs48/45 antigen. In the Burkina Faso study, ProC6C/Matrix-M became the first malaria vaccine to demonstrate functional transmission-reducing activity in humans from the Pfs48/45 antigen - where 13/20 (65%) volunteers immunized with 100 μg ProC6C-AlOH with Matrix-M, showed greater than 80% transmission reducing activity (TRA). Interim analysis of the second Phase 1 clinical trial conducted in Mali demonstrated similar findings. ProC6C/Matrix-M has also demonstrated the ability to induced high antibodies against the Circumsporozoite Protein (CSP), the leading malaria vaccine target to prevent parasite infection, in those same human volunteers. The ability of these CSP antibodies to prevent infection will now be assessed in this Phase 2 study.

“We’ve long known from preclinical data that Pfs48/45 would be a good transmission-blocking vaccine candidate,” said Professor Michael Theisen, SSI, who has led malaria vaccine development at SSI for decades: “Having confirmed that transmission objective in the Phase 1 studies, we are now excited to evaluate the ability of our short CSP sequence in that same immunogen to prevent infection.”

“The past years have taught us that having multiple interventions are critical to controlling disease, and the advancement of ProC6C/Matrix-M into efficacy trials is an exciting opportunity to offer another possible control measure through novel vaccine designs and collaborative approaches,” said Jordan Plieskatt, CSO, Praestans BioSciences, and Product Development lead for the project. “The PfTBV consortium founded in 2019 through funding by the European Union And Developing Countries Clinical Trials Partnership (EDCTP2) demonstrates the capabilities of the European-African partnerships to accelerate new candidates and strengthen capacities together.”

The Phase 1 data supported the robust enhancement of immune responses by the inclusion of the Matrix-M Adjuvant with ProC6C – and the ProC6C/Matrix-M combination was selected for further evaluation in this Phase 2 trial.

Phase 2 clinical trial

The randomized, double-blind Phase 2 clinical trial, termed “TBVax3” will be led by Dr. Issaka Sagara and conducted at the Malaria Research and Training Center (MRTC) together with the University of Sciences, Techniques and Technologies of Bamako (USTTB) in Sotuba, Mali, through the PfTBV consortium established in 2019.

“The PfTBV consortium was established to rapidly evaluate malaria vaccines from our US and European Partners, and our well-established centers in Mali have allowed just that,” said Dr. Issaka Sagara, coordinator of the EDCTP project and Principal Investigator of the Phase 2 study of ProC6C/Matrix-M: “We are well pleased to see new vaccines advance and the valuable contributions that our communities make to this endeavor.”

Healthy adults (18-50 years old) will receive three immunizations of ProC6C together with the Matrix-M adjuvant. Following the last vaccine dose, individuals will be “challenged” by direct infection with the P. falciparum malaria parasite and followed daily to determine the time to patent parasitemia (presence of parasite in the blood). The primary objectives of the study are to assess safety, tolerability, and the protective efficacy of ProC6C/Matrix-M against P. falciparum infection. Controlled Human Malaria Infection (CHMI) models are an established methodology for evaluating the efficacy of pre-erythrocytic and asexual blood-stage malaria vaccine candidates and drugs, both in malaria-naïve volunteers and in prior-exposed adults in malaria-endemic regions. Initial results are expected in late 2024 and the data will inform the advancement of ProC6C/Matrix-M as a standalone malaria vaccine.