Clinical Research Directory

A Study to Assess the Experimental Malaria Vaccines R78C and RH5.1 Combined With R21/Matrix-M (a "Multi-stage" Malaria Vaccine)

This is a Phase Ib age de-escalation, dose escalation, open-label study to assess the safety and immunogenicity of the multi-stage malaria vaccine candidate R21 plus RH5.1 and/or R78C in Matrix-M in adults aged 18-35 years and children aged 5-17 months in Burkina Faso.

A Study to Assess the Experimental Malaria Vaccines R78C and RH5.1 With Matrix-M in Combination With R21/Matrix-M

This is a Phase IIb randomised controlled trial of the safety, immunogenicity and efficacy of the malaria vaccine candidates R78C with Matrix-M™, and the combination of RH5.1 and R21 with Matrix-M™, in children aged 5-36 months in Burkina Faso.

Improving Neonatal Health Through Rapid Malaria Testing in Early Pregnancy With High-Sensitivity Diagnostics

The purpose of the INTREPiD study is to compare 1st trimester screening for malaria parasites with a high-sensitivity malaria rapid diagnostic test followed by treatment of test-positive women with artemether-lumefantrine (AL) against usual antenatal care on a composite adverse pregnancy outcome including low birth weight, small for gestational age, preterm, fetal loss, or neonatal death.

Safety and Immunogenicity of SUM-101 Malaria Vaccine in Children and Infants Living in Burkina Faso

This clinical trial aims to learn about the safety and immunogenicity of the blood-stage malaria vaccine candidate SUM-101 in infants and children, paving the way for its incorporation into a multi-stage malaria vaccine. This will be the first time SUM-101 will be evaluated for safety and immunogenicity in infants and children. The main questions it aims to answer are: * Are the 3 doses of full-length MSP1/GLA-SE (SUM-101) in young children and infants safe? * Do the 3 doses of full-length MSP1/GLA-SE (SUM-101) in young children and infants produce any reactogenicity? * How is the immunogenicity in young children and infants generated by the 3 doses of full-length MSP1/GLA-SE (SUM-101)? * What is the optimal dose of the full-length MSP1/GLA-SE (SUM-101) in young children and infants? The study will be divided into two arms with 5 groups conducted at a single centre. In total, 69 healthy malaria-pre-exposed infants and children aged 5 months to 5 years will be enrolled in this study. Participants will be included in one of the following groups: * Arm 1\_Group 1 (open-label design): This will be the first cohort enrolled to assess safety in children (18 months - 5 years) before the vaccination of infants commences. Therefore, all participants in Arm 1 will receive three doses of SUM-101 vaccine (25µg MSP1 + 5µg GLA-SE) on D0, D28 and D56. * Arm 2\_Group 2-5 (randomised, controlled, double-blind design): This will be the second cohort enrolled to assess safety in the target population (infants aged 5-17 months). Infants will be assigned to Groups 2-5 to enable evaluation of two doses of MSP1 (25µg and 10µg) and two doses of GLA-SE (5µg and 2.5µg). The infants in each group will be randomised into A) a vaccine arm (12 participants) and B) a control arm (3 participants). All participants in Groups 2-5 will receive three doses of either SUM-101 vaccine or Verorab® (Rabies vaccine) on D0, D28 and D56. Participants will visit the clinic for screening and once selected for enrolment. No later than 28 days after selection participants will receive the 1st vaccination (Visit Day 0) and 2nd and 3rd Vaccination on Day 28 and Day 56. On Day 1 to 6 days post each vaccination (Day 1-6, Day 29-34 and Day 57-62) each participant will be visited at home daily by a field worker for assessment and recording of any solicited and unsolicited AEs (Reactogenicity visits).

Preventing Malaria in School Children to Protect the Whole Community in Rural Blantyre District, Malawi

This is an individually randomized, controlled, single blind three arm clinical trial of malaria chemoprevention strategies Arm 1: Intermittent preventive treatment with dihydroartemisinin-piperaquine (IPT-DP). Arm 2: Intermittent preventive treatment with sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ) (IPT-SPAQ). Arm 3: Control - students will receive standard of care (no preventive treatment). Outcomes include P. falciparum infection and parasite density, anemia, cognitive function and educational testing, as well as infection prevalence and disease incidence in young children sleeping student's households to assess the impact on transmission.

A Phase 1 Study to Assess an Escalating Dose, Multi-prime Vaccination Schedule of R21/Matrix-M™

This is a phase I clinical study that aims to assess the safety and immunogenicity of a novel, escalating dose regimen of R21/Matrix-M™ in healthy, malaria-naïve adults.

An Observational Study to Assess Effectiveness and Safety of The R21/Matrix-M Malaria Vaccine

This is an observational case-control study to assess the effectiveness of the R21/Matrix-M vaccine against severe malaria, clinical malaria (in high transmission perennial areas), and to assess if the R21 vaccine recipients are at an increased risk of deaths (all-cause). Clinical malaria, severe malaria and death (all-cause) cases will be enrolled in study. For each case (severe or death) 4 controls matched for age and neighborhood will be enrolled whereas for clinical malaria case, 1 matched control will be enrolled. 1. Proportion of vaccinated and unvaccinated children amongst Severe Malaria Cases caused by P. falciparum. 2. Proportion of vaccinated and unvaccinated children amongst Clinical Malaria Cases in high-transmission perennial areas caused by P. falciparum. 3. Proportion of vaccinated and unvaccinated children in cases of death (all cause) 4. Exploratory effectiveness endpoint: Proportion of vaccinated and unvaccinated children in the hospitalized clinical and severe malaria cases.

A Study to Test Experimental Blood Stage Malaria Vaccine in Burkina Faso.

This is a Phase IIb randomised controlled trial of the safety, immunogenicity and efficacy of the blood-stage malaria vaccine candidates RH5.1 in Matrix-MTM and RH5.2-VLP in Matrix-MTM in infants aged 5-17 months in Burkina Faso

Pharmacokinetics of Antimalarials in Breastfeeding Ugandan Mother-infant Pairs

Lactating women requiring treatment for uncomplicated malaria will be identified and invited for sampling. The decision to treat them with first-line treatment will have been made by the clinician, not by a member of the study team. The study team will not make any adjustments to the prescribed treatment. Artemether-lumefantrine comprises six doses of medication, with the initial two doses given 8 hours apart on Day 1, and dosing 12-hourly on Day 2 and Day 3. Intensive pharmacokinetic sampling will be undertaken after Dose 5, as indicated in the schema under Section 5: plasma and breastmilk samples will be obtained pre-dose and at 2, 4, 6, 8 hours after dose. In addition, sparse sampling will be undertaken on either of these occasions; at pre-dose and between 1 to 6 hours after the first dose; a trough (pre-dose) sample after the Dose 3 or Dose 4 and lastly at 5, 7, and up to 14-days after the first dose. A heelprick sample will also be obtained from the breastfed infants at maternal trough (prior to maternal dose) and at a random timepoint (once per infant) over the 8-hour pharmacokinetic sampling visit to characterize concentrations of these drugs over an 8-hour dosing interval. In addition, a single heelprick sample will be obtained from the infant whenever the mother returns after treatment for the late sampling time points (5, 7, and 14 days post the first dose). Due to the long half-life of lumefantrine of approximately 6 days plasma sampling will be performed up to day 14 to characterise the terminal elimination of the drug. Concentrations of total plasma and breastmilk lumefantrine and desbutyl-lumefantrine will be determined.

Durability of Protection After Single Immunisation With GA2 Sporozoites (CoGA-Rechallenge)

This study will assess the durability of protection of a single immunisation with the Genetically Attenuated Parasite 2 (GA2) against controlled human malaria infection by rechallenging previously immunised and protected participants from the CoGA study (NCT05468606)

A Study to Assess the Safety and Effectiveness of Two Experimental Malaria Vaccines

Malaria is a major public health problem. There were around 240 million cases of malaria and 627,000 deaths worldwide in 2020. There is a great need for a safe, effective malaria vaccine and the team at University of Oxford is trying to make vaccine(s) which can prevent serious illness and death. This study is being done to assess an experimental malaria vaccine for its ability to prevent malaria illness. This is done using a 'blood-stage challenge model'. This is when volunteers are infected with malaria parasites using malaria-infected red blood cells. The vaccine we are testing in this part of the study is called "RH5.2-VLP". It is given with an adjuvant called "Matrix-M". This is a substance to improve the body's response to a vaccination. RH5.2-VLP is being tested for the first time in humans in this trial. The Matrix-M adjuvant has been given to tens of thousands of people, with no major concerns, such as illness. The aim is to use this vaccine and adjuvant to help the body make an immune response against parts of the malaria parasite. This study will assess: 1. The safety of the vaccine in healthy participants. 2. The response of the human immune system to the vaccine. 3. The ability of the vaccine to prevent malaria illness (Group 2 only). We will do this by giving healthy adult participants (aged 18-45) three of the vaccines and/or expose participants to malaria infection at the Centre for Clinical Vaccinology and Tropical Medicine (CCVTM), Churchill Hospital in Oxford. We will then do blood tests and collect information about any symptoms that occur after vaccination. There will be 19 to 54 visits, lasting between 3 months to 2 years and 2 months.

A Study to Compare Two Dosing Regimens for a New Malaria Vaccine

Malaria is a major public health problem. There were around 240 million cases of malaria and 627,000 deaths worldwide in 2020. Most of the deaths are in children under five living in Africa. It is a major problem for those who live in affected areas and for travellers. There is a great need for a safe, effective malaria vaccine. This study is being done to evaluate an experimental malaria vaccine for its safety and also look at the body's immune response to the vaccine. The vaccine tested in this study is called and "RH5.1". This is given with an adjuvant called "Matrix-M". This is a substance to improve the body's response to a vaccination. The aim is to use the vaccines and adjuvant to help the body make an immune response against parts of the malaria parasite. This study will assess: 1. The safety of the vaccines in healthy participants. 2. The response of the human immune system to the vaccines. This will be achieved by giving participants three doses of the RH5.1 vaccines at two different dose levels (10 micrograms and 50 micrograms). One group will have 3 doses of 10 micrograms given at 0, 1 and 6 months whilst the other will receive 2 doses of 50 micrograms (at 1 and 2 months) followed by a 10 microgram dose at 6 months- known as a 'delayed fractional dose'. Blood tests and information about any symptoms will be performed/collected that occur after vaccination. Information from previous studies suggests that a delayed fractional dose improves the immune response to the vaccine, particularly in terms of the antibody response. Current prediction is that this improvement is due to the delay in dosing, rather than the reduction in dose, and this study will help to answer that. Having a vaccine at a single dose is important for efficient production and dosing for vaccines rolled out in national programs so being able to move away from 'delayed fractional dose' regimens to 'delayed final dose' regimens will be important for vaccine development.

Host Immune Dynamics Following Seasonal Malaria Chemoprevention in African Children

The study aims to identify immune features linked to protection against malaria, examining variations by age and sex, and measuring changes in immune responses over time following seasonal malaria chemoprevention (SMC). The primary objectives are: 1. Thorough examination of antibody immune responses in individuals before and after one or more SMC rounds. 2. Thorough examination of both innate and adaptive cellular immune responses in people residing in areas with regular SMC use. Participants will include children aged 3 to 59 months who have received at least two or three SMC rounds, as well as children aged 5 to 15 years with no prior SMC exposure. Upon identifying participants, study details will be provided, and written informed consent obtained. Demographic and clinical information will be collected using standard case record forms, including previous SMC uptake and routine malaria control interventions. Information on SMC use will be obtained from SMC cards/existing medical records, detailing the number of cycles received, adherence, and general health condition, including previous diseases and EPI vaccine uptake. Data Collection: * Face-to-face interviews by trained research assistants. * Clinical assessments, including temperature, weight, and mid-upper arm circumference (MUAC). * Sickle cell status testing at enrolment via samples analyzed at the Molecular Research Laboratory (MOLAB). * Hemoglobin measurement using a HemoCue analyzer. Malaria Diagnosis: * Blood samples collected for malaria diagnosis using rapid diagnostic tests (RDTs) and microscopy. * RDTs, such as Paracheck Pf, will be performed according to manufacturer instructions, with results available within 15 minutes. * Participants testing positive for malaria will receive a full course of antimalarial treatment and counselling to visit the nearest health facility if symptoms worsen. Thick Blood Smears: * New glass slides labelled with participant ID will be used for thick blood smears. * Blood smears will be dried and stored in a cool, dust-free environment before transportation to central laboratories. * Slides will be stained with 2% Giemsa for 30 minutes and evaluated for parasitemia and gametocytes, with densities calculated accordingly. The study will help understand the immune responses to malaria and the efficacy of SMC in different age groups.

The Impact RTS,S/AS01 Vaccine in School Aged Children RTS,S/AS01 Malaria Vaccine in School Aged Children

Across sub-Saharan Africa, school-age children bear an under-appreciated burden of malaria. An estimated 200 million school-age children are at risk of malaria and in many areas prevalence of infection exceeds 50%. The high infection rates in this group serves as a source of onward parasite transmission, undermining elimination and control efforts. Furthermore, malaria illness and malaria-induced anemia in this age group lead to school absenteeism, and impaired cognitive function and classroom attention, ultimately resulting in reduced academic achievement. Although universal malaria interventions, such as insecticide treated nets (ITNs) and access to prompt diagnosis and treatment are available to school-age children, this age group is the least likely to benefit from these interventions. Furthermore, efficacy of these approaches may be compromised by increasing anti-malarial drug and insecticide resistance. A malaria vaccine could help to avert the burden of malaria in this age group. The RTS,S/AS01 malaria vaccine has recently been recommended for vaccination of young children (\< 24 months) by the World health organization (WHO) after a Phase 3 trial and an implementation trial showed that the vaccine had moderate but significant efficacy to prevent clinical and severe malaria in young children. Previous randomized trials suggest that the vaccine is safe for older children. However, efficacy of the vaccine has never been assessed in school age children. Kamuzu University of Health Sciences in partnership with the Malawian Ministry of Health seeks to evaluate the efficacy of the newly introduced RTSS/AS01 malaria vaccine in school aged children. The study hypothesizes that vaccination will decrease the morbidity and transmission of malaria, as well as improve school absenteeism and educational outcomes.

Addressing Asymptomatic Plasmodium Reservoirs to Accelerate Malaria Elimination and Eradication in Rwanda.

The investigators believe that to effectively achieve malaria elimination in Rwanda, it is critical to target the human reservoirs of Plasmodium falciparum using local and readily available Artemisia tea. Asymptomatic infections detectable by PCR are important reservoirs because they often persist for months and harbor gametocytes, the parasite stage infectious to mosquitoes. Lessons learnt from this study will be of critical importance for health decision makers with regard to potential malaria control. MSc and PhD students will be trained and the impact of this research project will be enormous on the socioeconomic transformation of Rwanda.