NCT04661579

Study of Malaria Vaccine RTS,S/AS01E in Plasmodium Falciparum-infected and Uninfected Adults Pre-treated With Anti-malarial Therapy

A Phase 2b Randomized, Open-label, Controlled, Single Center Study in Plasmodium Falciparum-infected and Uninfected Adults Age 18-55 Years Old in Kenya to Evaluate the Efficacy of the Delayed, Fractional Dose RTS,S/AS01E Malaria Vaccine in Subjects Treated With Artemisinin Combination Therapy Plus Primaquine

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 620 (actual)
• Sponsor: PATH · Academic / Other
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

The main goal of this study is to assess the efficacy of RTS,S/AS01E, a candidate vaccine against malaria caused by Plasmodium falciparum (P. falciparum), in adults positive for P. falciparum at the start of the study, but treated with anti-malarial medications to clear the parasite before receiving multiple doses of the vaccine. The goal is to overcome the reduced vaccine efficacy (hypo-responsiveness to the vaccine) reported in actively or chronically infected adults.

Detailed description

PATH and GlaxoSmithKline (GSK) are committed to developing a malaria vaccine to help reduce the burden of malaria disease in children and contribute to malaria elimination. GSK has developed a candidate vaccine against malaria caused by P. falciparum called RTS,S/AS01E. The vaccine has been shown to be safe in multiple trials and efficacy data in pediatric populations has led to a pilot implementation program in three African countries including Kenya. The RTS,S/AS01E vaccine mechanism of action is presumed to work on the initial sporozoite and liver stages of P. falciparum infection through neutralization of the circumsporozoite (CS) antigen on parasites invading after a mosquito bite in individuals immunized with the RTS,S/AS01E vaccine. In order to inform whether a vaccine such as RTS,S/AS01E may have a future role in malaria elimination, it will be important to establish vaccine efficacy in adults in Sub-Saharan Africa who are reservoirs of parasites and who contribute to ongoing malaria transmission. However, in previous trials, the vaccine has been less effective in adults who have had malaria before. There are probably multiple reasons for this, but one possible reason that is probably very important is that prior infection with malaria or an infection with malaria for long periods, even without symptoms of the disease, can prevent the vaccine from working properly. This study postulates that treatment of infection prior to immunization can reset the immune response leading to an improved vaccine efficacy. To evaluate this hypothesis, the study will recruit 5 groups. Groups 1 and 4 will have asymptomatic infection with P. falciparum as measured by a highly sensitive polymerase chain reaction (PCR) assay and will be treated with antimalarial medications prior to immunization with RTS,S/AS01E or the comparator rabies vaccine, respectively, with the primary objective of evaluating the vaccine efficacy of RTS,S/AS01E relative to the rabies vaccine in this context. Groups 2 and 5 will be negative for asymptomatic infection with P. falciparum as measured by a highly sensitive PCR assay and will be treated with antimalarial medications prior to immunization with RTS,S/AS01E or the comparator rabies vaccine, respectively, with the secondary objective of evaluating the vaccine efficacy of RTS,S/AS01 relative to the rabies vaccine in this context. Group 3 will have asymptomatic infection with P. falciparum as measured by a highly sensitive PCR assay but will not be treated with antimalarial medications prior to immunization with the RTS,S/AS01E vaccine; the immunological profile of this group and groups 1 and 2 will be evaluated as part of secondary and exploratory objectives. Other secondary objectives include safety assessments. The study will include an initial immunization period (vaccine given on 0, 1, and 7 month schedule with the final dose being 1/5 of the dose of the first two immunizations) followed by 6-12 months of follow-up (varying based on the number of events),

Conditions

• Plasmodium Falciparum

Interventions

Type	Name	Description
BIOLOGICAL	Malaria Vaccine RTS,S/AS01E	RTS,S/AS01E vaccine 0.5 mL, containing 25 μg protein comprising circumsporozoite protein (CS) and hepatitis B surface antigen (RTS,S), 25 μg monophosphoryl lipid (AMPL), 25 μg Quillaja saponaria 21 (QS21) in a liposomal formulation) for the first two immunizations. One-fifth dose RTS,S/AS01E vaccine was used for the third immunization.
BIOLOGICAL	Abhayrab rabies vaccine	Abhayrab rabies vaccine, 0.5 mL, contains 2.5 IU rabies antigen.
DRUG	Dihydroartemisinin-piperaquine (DHA/Pip)	Dihydroartemisinin (120 mg or 160 mg based on weight) and piperaquine tetraphosphate (960 mg or 1280 mg based on weight) mg) administered once a day for 3 days. DHA/Pip is a long acting anti-malarial used to clear asexual stage and young gametocyte parasites.
DRUG	Artemether / Lumefantrine	Artemether (80 mg) and lumefantrine (480 mg) administered twice a day for 3 days. Coartem is a short-acting artemisinin combination therapy used to provide clearance of blood stage parasites in order to establish a clean baseline for determination of vaccine efficacy.
DRUG	Primaquine	One dose of 15 mg primaquine. Low dose primaquine (LD PQ) is used to clear mature gametocytes of P. falciparum.

Timeline

• Start date: 2020-11-06
• Primary completion: 2022-06-22
• Completion: 2022-08-17
• First posted: 2020-12-10
• Last updated: 2024-07-19
• Results posted: 2024-07-19

Locations

1 site across 1 country: Kenya