Phase 2 N=193 Randomized Prevention

Malaria Vaccine Safety and Immunogenicity Study in Healthy Adults

Malaria Vaccine

Bottom Line

View on ClinicalTrials.gov: NCT02992119 ↗

Enrolled (actual)

193

Serious AEs

1.6%

Results posted

Jul 2019

Primary outcome: Primary: Number of Participants Who Experience a Serious Adverse Events (SAEs) 29 Days After the Last Vaccination — 1; 0; 0; 1 Participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: RTS,S/AS01B Fractional dose (Biological); Double RTS,S/AS01E Fractional dose (Biological); RTS,S/AS01E Standard dose (Biological); RTS,S/AS01E + DHA-PIP+PQ Standard dose (Biological); RTS,S/AS01E Fractional dose (Biological); RTS,S/AS01E + DHA-PIP+PQ Fractional dose (Biological); RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose (Biological)
Age: Adult · 18+ yrs
Sex: All
Sponsor: University of Oxford
Primary completion: Feb 2018

Outcome Measures

Outcome	Result	p-value
PRIMARY Number of Participants Who Experience a Serious Adverse Events (SAEs) 29 Days After the Last Vaccination	1; 0; 0; 1; 1; 0	—
PRIMARY Number of Participants Who Experience a Serious Adverse Events (SAEs) During a 6 Month Follow up Period From the Receipt of First Vaccination	1; 0; 0; 1; 1; 0	—
PRIMARY Number of Participants Who Seroconverted One Month After First Dose.	20; 20; 29; 30; 28; 29	—
PRIMARY Number of Participants Who Seroconverted One Month After the Second Dose.	19; 20; 30; 30; 30; 30	—
PRIMARY Number of Participants Who Seroconverted One Month After the Third Dose.	20; 20; 30; 30; 30; 30	—
PRIMARY Number of Participants Who Seroconverted at Month Six After First Dose.	19; 20; 29; 30; 30; 30	—
PRIMARY Number of Participants Who Received RTS,S/AS01E + DHA-PIP+PQ Fractional Two-dose (Group 7) That Seroconverted at Month Two After First Dose.	30	—

Summary

Targeted malaria elimination (TME), which comprises appropriate case management by village health workers, vector control and mass drug administration, is currently being implemented through pilot projects in selected villages in the Greater Mekong Subregion (GMS) and the scale-up of the intervention to the regional level are underway. Based on mathematical modelling, extending the post-TME parasitaemia-free period in the majority of villagers for as short as 200 days will substantially increase the chances of achieving the interruption of malaria transmission. Immunogenicity of RTS,S is greater in older children, and the short term malaria protective effect is stronger than the overall effect assessed over 1-2 years. Addition of mass RTS,S/AS01E vaccination to the TME arsenal could provide this much needed additional protection. Currently there are no safety and immunogenicity data for the use of RTS,S/AS01 in Asian populations. This trial will generate the required data for the use of this vaccine in Asian populations. For integration with the current TME activities, which provide mass drug administrations at months M0, M1, and M2, it would be most efficient and practical to provide the vaccine at the same intervals. To address a two round intervention (M0, M2) where a three round intervention is not feasible, one study arm will look at the immune response generated by only two doses of vaccine and antimalarial medications. Recent evidence suggests that a vaccination schedule which includes a fractional dose of RTS,S/AS01 (1/5th of the standard dose) could be similarly or more protective than a schedule with three standard full doses, while requiring less vaccine and resources. The trial therefore includes study arms which will assess the safety and immunogenicity of fractional dose schedules. Each participant will be randomized into one of the following study arms in a ratio of 20:20:30:30:30:30:30, as follows: * RTS,S/AS01B Fractional dose group (Group 1) * Double RTS,S /AS01E Fractional dose group (Group 2) * RTS,S/AS01E Standard dose group (Group 3) * RTS,S/AS01E + DHA-PIP+PQ Standard dose group (Group 4) * RTS,S/AS01E Fractional dose group (Group 5) * RTS,S/AS01E + DHA-PIP+PQ Fractional dose group (Group 6) * RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose group (Group 7)

Eligibility Criteria

Inclusion Criteria

Participant is a healthy male or non-pregnant female, aged 18 to 55 years (inclusive), of Thai origin.
Participant is willing and able to give informed consent to participate in the trial
Able, in the investigators opinion, and willing to comply with the study requirements and follow-up.

Exclusion Criteria

Female participant who is pregnant, lactating or planning pregnancy during the course of the study.
Presence of any condition which in the judgment of the investigator would place the participant at undue risk or interfere with the results of the study (e.g. serious underlying cardiac, renal, hepatic or neurological disease; severe malnutrition; congenital defects or febrile condition).
Hepatitis B surface antigen (HBsAg) detected in serum.
Screening ECG demonstrates a QTc interval ≥ 450 ms
Seropositive for hepatitis C virus (antibodies to HCV) at screening (unless has taken part in a prior hepatitis C vaccine study with confirmed negative HCV antibodies prior to participation in that study, and negative HCV RNA PCR at screening for this study).
Anaemia (Hb 20 mg/day (for adult subjects), or equivalent. Inhaled and topical steroids are allowed.
Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting seven days before the first dose.
Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
History of splenectomy.
Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection or based on medical history and physical examination.
History of anaphylaxis post-vaccination.
Serious chronic illness.
Any abnormal baseline laboratory screening tests: ALT, AST, creatinine, haemoglobin, platelet count, total WBC, out of normal range as defined in the protocol.
Hepatomegaly, right upper quadrant abdominal pain or tenderness.
Personal history of autoimmune disease.
Administration of immunoglobulins and/or any blood products during the period starting three months before the first dose of study vaccine or planned administration during the study period.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02992119). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.