Safety and Immunogenicity of the Malaria Vaccine, R21/MatrixM, in Healthy Thai Adults

NCT05252845 | Completed Phase 2 Results DMC

• 2 other identifiers: MAL22001MR/T006161/1
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

Brief Summary

Malaria remains one of the leading causes of morbidity and mortality worldwide. Plasmodium falciparum is a complex pathogen with numerous immune evasion mechanisms which has added layers of complexity to the development of safe and protective vaccines. There remains an urgent need to identify and develop more protective and more affordable vaccine candidates that could achieve the World Health Organization (WHO) goal of 75% efficacy against clinical malaria. R21 is a novel pre-erythrocytic candidate malaria vaccine. R21 includes Hepatitis B surface antigen (HBsAg) fused to the C-terminus and central repeats of the circumsporozoite protein of P. falciparum (CSP), which self-assemble into virus-like particles in yeast. R21 lacks the excess HBsAg found and comprises only fusion protein moieties. R21/MatrixM (MM) had a favourable safety profile and was well tolerated. The majority of adverse events were mild, with the most common event being fever. None of the serious adverse events were attributed to the vaccine. At one year, vaccine efficacy remained high, at 77%. Participants vaccinated with R21/MM showed high titres of malaria-specific anti- Asn-Ala-Asn-Pro (NANP) antibodies 28 days after the third vaccination, which were almost doubled with the higher adjuvant dose. Titres waned but were boosted to levels similar to peak titres after the primary series of vaccinations after a fourth dose administered one year later. Currently, there are no safety and immunogenicity data for the use of R21/MatrixM in Asian populations. This trial will generate the required data for the use of this vaccine in Asia. For integration with the current targeted malaria elimination (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. In summary: The investigators propose to conduct a safety and immunogenicity trial of R21/MatrixM in Thai adults. The major aims of this study are to 1) assess the safety and immunogenicity of R21/MatrixM in Thai adults 2) confirm that the co-administration of antimalarial drugs with the malaria vaccine R21/MatrixM does not reduce the immunogenicity of the vaccine and 3) assess the absorption and pharmacokinetics of antimalarial drugs piperaquine, and a single low dose of primaquine (SLDPQ) when co-administered with R21/MatrixM. This is a randomized, open label, single centre, Phase 2 study. 120 healthy non-pregnant Thai adults, aged 18-55 years, inclusive, will be recruited. Each participant will be randomized into one of the following study arms in a ratio of 5:5:2, as follows:

1. 1.R21/MatrixM + Dihydroartimisinin (DHA)-Piperaquine (PIP)+ primaquine (PQ) (Group 1, n=50) will receive R21/MatrixM + 3 doses DHA-PIP+PQ at Month 0, Month 1 and Month 2
2. 2.R21/MatrixM only (Group 2, n=50) will receive R21/MatrixM standard dose at Month 0, Month 1 and Month 2
3. 3.DHA-PIP+PQ only (Group 3, n=20) will receive 3 doses DHA-PIP+PQ at Month 0, Month 1 and Month 2

Conditions

Malaria,Falciparum

Keywords

Malaria vaccine; Immunogenicity of the malaria vaccine; Immunologic response to malaria vaccine

Outcome Measures

Primary Outcomes (3)

• Occurrence of Unsolicited Adverse Events (AEs), According to the Medical Dictionary for Regulatory Activities (MedRA) Classification.

  From the date of the first vaccination to 28 days after the last vaccination (up to approximately 1 month)

• Occurrence of Serious Adverse Events (SAEs), According to the MedRA Classification.

  During the whole study period, i.e. during a 6-month follow-up period from the receipt of first vaccination

• Occurrence of Solicited Adverse Event Within 7 Days of Each Vaccination

  Within 7 days of each vaccination.

Secondary Outcomes (22)

• Number of Participants With Seroconversions in C-Term

  at study Month 1

• Number of Participants With Seroconversions in C-Term

  at study Month 2

• Number of Participants With Seroconversions in C-Term

  at study Month 3

• Number of Participants With Seroconversions in C-Term

  at study Month 6

• Number of Participants With Seroconversions in NANP

  at study Month 1

Study Arms (3)

R21/Matrix-M + DHA-PIP+PQ

EXPERIMENTAL

The R21/Matrix-M vaccine (IM injection) + co-formulated Dihydroartemisinin/Piperaquine tablets + one single low dose of Primaquine

Biological: R21/Matrix-M vaccination; Drug: DHA-PIP; Drug: PQ

R21/Matrix-M only

EXPERIMENTAL

The R21/Matrix-M vaccine (IM injection) only

Biological: R21/Matrix-M vaccination

DHA-PIP+PQ only

ACTIVE COMPARATOR

Co-formulated Dihydroartemisinin/Piperaquine tablets + one single low dose of Primaquine

Drug: DHA-PIP; Drug: PQ

Interventions

R21/Matrix-M vaccination BIOLOGICAL

R21/Matrix-M is the standard formulation of the vaccine (Once prepared, a standard dose of R21/Matrix-M contains approximately 5 µg of R21 antigen, in 0.5 mL of liquid adjuvant containing 50 µg MatrixM). The reconstituted vaccine will be administered by slow IM injection on Day 0 at Study Months 0, 1 and 2.

R21/Matrix-M + DHA-PIP+PQ; R21/Matrix-M only

DHA-PIP DRUG

Dihydroartemisinin/piperaquine tablets for adult patients each contain 40 mg dihydroartemisinin and 320 mg piperaquine with a therapeutic dose range between 2-10 mg/kg/day dihydroartemisinin and 16-26 mg/kg/dose piperaquine. Participants will receive three rounds of antimalarial drugs - each round starting on the day of vaccination (Day 0) at Study Months 0, 1 and 2. Each round consists of three daily doses of co-formulated dihydroartemisinin/piperaquine on Day 0, 1, and 2.

DHA-PIP+PQ only; R21/Matrix-M + DHA-PIP+PQ

PQ DRUG

Each participant will receive a single low dose primaquine on the day of vaccination (Day 0) at Month 0, Month 1, and Month 2. One single low dose primaquine of approximately 0.25 mg/kg will be administered.

DHA-PIP+PQ only; R21/Matrix-M + DHA-PIP+PQ

Eligibility Criteria

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

You may qualify if:

• The participant is eligible to enter the study if all of the following apply:
• Participant is a healthy adult, 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 investigator's opinion, and willing to comply with the study requirements and follow-up.
• Women of childbearing potential: must agree to practice continuous, effective contraception for the duration of the trial, and have a negative pregnancy test before each vaccination. (Costs for contraceptives will be reimbursed by the trial.)

You may not qualify if:

• Pregnancy or breastfeeding, or planned pregnancy during the course of the study.
• Presence of any medical condition (physical or mental) which, may place the participant at undue risk or interfere with the results of the study\*. Including: serious cardiac, renal, hepatic or neurological disease, severe malnutrition
• Any confirmed or suspected immunosuppressive or immunodeficient condition. Including: history of splenectomy, human immunodeficiency virus (HIV) infection
• Chronic administration (\>14 days in total) of immunosuppressants or other immune-modifying drugs within six months of enrollment. Including: oral corticosteroids equivalent to prednisone \> 20 mg/day (a)
• History of an autoimmune disease
• Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody(b) detected in serum.
• Screening electrocardiogram (ECG) demonstrating a QTc interval ≥ 450 ms
• Seropositivity for hepatitis C virus (antibodies to HCV) at screening (b)
• Finding on safety laboratory values as defined below:
• AST \> 2 x upper normal limit
• ALT \> 2 x upper normal limit
• Anaemia (Hb \< 10 g/dL),
• Platelets \< 150,000
• Total bilirubin \> 2 x upper normal limit
• Abnormalities of examination or investigations at screening. Including: hepatomegaly, right upper quadrant abdominal pain or tenderness, abnormal blood tests (as defined in the protocol which are not listed above)

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

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

Bangkok, 10400, Thailand

Location

MeSH Terms

Conditions

Malaria, Falciparum

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Results Point of Contact

• Title: Professor Lorenz von Seidlein
• Organization: Mahidol-Oxford Tropical Medicine Research Unit (MORU)

Lorenz@tropmedres.ac

+66-(0)2-3549170

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

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: February 23, 2022
• Study Start: January 4, 2023
• Primary Completion: June 8, 2023
• Study Completion: September 18, 2023
• Last Updated: July 3, 2025
• Results First Posted: July 3, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: After completion of trial activities and reporting

Locations

TH (1)