Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Malaria Vaccine Safety and Immunogenicity Study in Healthy Adults (RTSS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02992119
Recruitment Status : Completed
First Posted : December 14, 2016
Results First Posted : July 29, 2019
Last Update Posted : July 29, 2019
Sponsor:
Information provided by (Responsible Party):
University of Oxford

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)

Condition or disease Intervention/treatment Phase
Malaria Vaccine Biological: 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 Phase 2

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 193 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized 7 groups
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Safety and Immunogenicity Evaluation of the Malaria Vaccine, RTS,S/AS01, in Healthy Thai Adults
Actual Study Start Date : June 4, 2017
Actual Primary Completion Date : February 20, 2018
Actual Study Completion Date : February 20, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: Group 1
RTS,S/AS01B Fractional dose
Biological: RTS,S/AS01B Fractional dose
RTS,S/AS01B standard dose at Month 0 and Month 1 + RTS,S/AS01B fractional dose (1/5th dose) at Month 2.

Experimental: Group 2
Double RTS,S/AS01E Fractional dose
Biological: Double RTS,S/AS01E Fractional dose
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.

Experimental: Group 3
RTS,S/AS01E Standard dose
Biological: RTS,S/AS01E Standard dose
RTS,S/AS01E standard dose at Month 0, Month 1 and Month 2.

Experimental: Group 4
RTS,S/AS01E + DHA-PIP+PQ Standard dose
Biological: RTS,S/AS01E + DHA-PIP+PQ Standard dose
RTS,S/AS01E standard dose + DHA-PIP+PQ at Month 0, Month 1 and Month 2

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

Experimental: Group 6
RTS,S/AS01E + DHA-PIP+PQ Fractional dose
Biological: RTS,S/AS01E + DHA-PIP+PQ Fractional dose
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.

Experimental: Group 7
RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose
Biological: RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose
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




Primary Outcome Measures :
  1. Number of Participants Who Experience a Serious Adverse Events (SAEs) 29 Days After the Last Vaccination [ Time Frame: 29 days after 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.

  2. Number of Participants Who Experience a Serious Adverse Events (SAEs) During a 6 Month Follow up Period From the Receipt of First Vaccination [ Time Frame: 6 months ]
    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.

  3. Number of Participants Who Seroconverted One Month After First Dose. [ Time Frame: 1 months ]
    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).

  4. Number of Participants Who Seroconverted One Month After the Second Dose. [ Time Frame: 2 months ]
    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).

  5. Number of Participants Who Seroconverted One Month After the Third Dose. [ Time Frame: 3 months ]
    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. Number of Participants Who Seroconverted at Month Six After First Dose. [ Time Frame: 6 months ]
    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).

  7. Number of Participants Who Received RTS,S/AS01E + DHA-PIP+PQ Fractional Two-dose (Group 7) That Seroconverted at Month Two After First Dose. [ Time Frame: 2 months ]
    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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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 < 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.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02992119


Locations
Layout table for location information
Thailand
Hospital of Tropical Diseases, Faculty of Tropical Medicine, Mahidol University
Bangkok, Thailand, 10400
Sponsors and Collaborators
University of Oxford
Investigators
Layout table for investigator information
Principal Investigator: Lorenz von Seidlein, MD Mahidol Oxford Tropical Medicine Research Unit
  Study Documents (Full-Text)

Documents provided by University of Oxford:
Study Protocol  [PDF] November 2, 2017
Statistical Analysis Plan  [PDF] February 28, 2018

Layout table for additonal information
Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT02992119    
Other Study ID Numbers: BAKMAL1605
First Posted: December 14, 2016    Key Record Dates
Results First Posted: July 29, 2019
Last Update Posted: July 29, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Oxford:
safety
immunogenicity
Additional relevant MeSH terms:
Layout table for MeSH terms
Malaria
Protozoan Infections
Parasitic Diseases
Infections
Vector Borne Diseases