Malaria Vaccine Safety and Immunogenicity Study in Healthy Adults

NCT02992119 | Completed Phase 2 Results DMC

• 1 other identifier: BAKMAL1605
• Study Type: interventional
• Target: 193
• Locations: 1 country
• Sites: 1

Brief 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)

Conditions

Malaria Vaccine

Keywords

safety; immunogenicity

Outcome Measures

Primary Outcomes (7)

• Number of Participants Who Experience a Serious Adverse Events (SAEs) 29 Days After the Last Vaccination

  Occurrence of serious adverse events (SAEs) from the date of the first vaccination to 29 days after the last vaccination, according to the MedRA classification.

  29 days after last vaccination

• Number of Participants Who Experience a Serious Adverse Events (SAEs) During a 6 Month Follow up Period From the Receipt of First Vaccination

  Occurrence of SAEs during the whole study period, i.e. during a 6 month follow up period from the receipt of first vaccination, according to the MedRA classification.

  6 months

• Number of Participants Who Seroconverted One Month After First Dose.

  The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).

  1 months

• Number of Participants Who Seroconverted One Month After the Second Dose.

  The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).

  2 months

• Number of Participants Who Seroconverted One Month After the Third Dose.

  The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).

  3 months

• Number of Participants Who Seroconverted at Month Six After First Dose.

  The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).

  6 months

• Number of Participants Who Received RTS,S/AS01E + DHA-PIP+PQ Fractional Two-dose (Group 7) That Seroconverted at Month Two After First Dose.

  The percentage of subjects seroconverting after each immunization based on a value greater than the mean titer at baseline (before immunization # 1) plus 2 standard deviations for all subjects included in the analysis (ITT).(For group 7)

  2 months

Study Arms (7)

Group 1

EXPERIMENTAL

RTS,S/AS01B Fractional dose

Biological: RTS,S/AS01B Fractional dose

Group 2

EXPERIMENTAL

Double RTS,S/AS01E Fractional dose

Biological: Double RTS,S/AS01E Fractional dose

Group 3

EXPERIMENTAL

RTS,S/AS01E Standard dose

Biological: RTS,S/AS01E Standard dose

Group 4

EXPERIMENTAL

RTS,S/AS01E + DHA-PIP+PQ Standard dose

Biological: RTS,S/AS01E + DHA-PIP+PQ Standard dose

Group 5

EXPERIMENTAL

RTS,S/AS01E Fractional dose

Biological: RTS,S/AS01E Fractional dose

Group 6

EXPERIMENTAL

RTS,S/AS01E + DHA-PIP+PQ Fractional dose

Biological: RTS,S/AS01E + DHA-PIP+PQ Fractional dose

Group 7

EXPERIMENTAL

RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose

Biological: RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose

Interventions

RTS,S/AS01B Fractional dose BIOLOGICAL

RTS,S/AS01B standard dose at Month 0 and Month 1 + RTS,S/AS01B fractional dose (1/5th dose) at Month 2.

Group 1

Double RTS,S/AS01E Fractional dose BIOLOGICAL

A double dose of RTS,S/AS01E standard dose at Month 0 and Month 1 + a double dose of RTS,S/AS01E fractional dose (1/5th dose) at Month 2.

Group 2

RTS,S/AS01E Standard dose BIOLOGICAL

RTS,S/AS01E standard dose at Month 0, Month 1 and Month 2.

Group 3

RTS,S/AS01E + DHA-PIP+PQ Standard dose BIOLOGICAL

RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0, Month 1 and Month 2

Group 4

RTS,S/AS01E Fractional dose BIOLOGICAL

RTS,S/AS01E standard dose at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) at Month 2.

Group 5

RTS,S/AS01E + DHA-PIP+PQ Fractional dose BIOLOGICAL

RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 and Month 1 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2.

Group 6

RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose BIOLOGICAL

RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0 + RTS,S/AS01E fractional dose (1/5th dose) + DHA-PIP+PQ at Month 2

Group 7

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 \< 10 g/dL)
• Positive malaria parasitaemia at screening or baseline (Month 0, Day 0).
• Use of any investigational or non-registered product or investigational use of a registered product (drug or vaccine), other than the study vaccines, during the period from the date of screening to the first vaccination, or planned use during the study period.
• Any medical condition that in the judgment of the investigator would make intramuscular (IM) injection unsafe.
• Any medical condition that in the judgment of the investigator would make the administration of the antimalarial treatment unsafe, such as prior allergic reactions to one or more component of the drug regimen: artemisinins, piperaquine or primaquine.
• Contraindications to the use of artemisinins, piperaquine or primaquine or use of medications known to have a potentially clinically significant interaction with these medications.
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone \> 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.

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Hospital of Tropical Diseases, Faculty of Tropical Medicine, Mahidol University

Bangkok, 10400, Thailand

Location

MeSH Terms

Interventions

RTS malaria vaccine

Results Point of Contact

• Title: Lorenz von Seidlein
• Organization: MORU

Lorenz@tropmedres.ac

662036663

Study Officials

• Lorenz von Seidlein, MD

  Mahidol Oxford Tropical Medicine Research Unit

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized 7 groups

Study Record Dates

• First Submitted: November 15, 2016
• First Posted: December 14, 2016
• Study Start: June 4, 2017
• Primary Completion: February 20, 2018
• Study Completion: February 20, 2018
• Last Updated: March 31, 2022
• Results First Posted: July 29, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share

Locations

TH (1)