A Study of the Plasmodium Falciparum Malaria Vaccine Candidate Pfs48/45 in Matrix-M Adjuvant in the UK

NCT05400746 | Terminated Early Phase 1 Results DMC

• 1 other identifier: VAC085
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, single-site, first-in-human, dose-escalation Phase Ia study to assess safety and immunogenicity of the Plasmodium falciparum malaria vaccine candidate Pfs48/45 in Matrix-M adjuvant in healthy adults living in the UK

Conditions

Malaria; Plasmodium Falciparum

Keywords

Pfs48/45; Matrix-M

Outcome Measures

Primary Outcomes (6)

• Safety and Tolerability of the Pfs48/45 With Matrix-M Vaccine at Various Doses in Healthy Adult Volunteers by Assessing the Occurrence of Solicited Local Reactogenicity Signs and Symptoms for 7 Days Following Each Vaccination

  Occurrence of solicited local reactogenicity signs and symptoms for 7 days following each vaccination using e-diaries, clinical review, clinical examination (including observations) and laboratory results

  7 days following each vaccination

• Safety and Tolerability of the Pfs48/45 With Matrix-M Vaccine at Various Doses in Healthy Adult Volunteers by Assessing the Occurrence of Solicited Systemic Reactogenicity Signs and Symptoms for 7 Days Following Each Vaccination

  Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following each vaccination using e-diaries, clinical review, clinical examination (including observations) and laboratory results.

  7 days following each vaccination

• Safety and Tolerability of the Pfs48/45 With Matrix-M Vaccine at Various Doses in Healthy Adult Volunteers by Assessing the Occurrence of Unsolicited Adverse Events (AEs) for 28 Days Following the Vaccination

  Number of unsolicited adverse events (AEs) for 28 days following the vaccination using e-diaries, clinical review, clinical examination (including observations) and laboratory results

  28 days following the vaccination

• Safety and Tolerability of the Pfs48/45 With Matrix-M Vaccine at Various Doses in Healthy Adult Volunteers. Assessed Through the Number of Participants With Abnormal Laboratory Test Results

  Occurrence of change from baseline laboratory tests

  28 days following vaccination

• Safety and Tolerability of the Pfs48/45 With Matrix-M Vaccine at Various Doses in Healthy Adult Volunteers Assessed Through the Number of Participants With Serious Adverse Events

  Occurrence of serious adverse events will be presented according to local grading scales

  Whole duration of the study (8 months following initial trial vaccination)

• Safety and Tolerability of the Pfs48/45 With Matrix-M Vaccine at Various Doses in Healthy Adult Volunteers.

  Occurrence of AEs of special interest will be presented according to local grading scales and will be described in detail

  Whole duration of the study (8 months following initial trial vaccination)

Secondary Outcomes (4)

• Humoral Immunogenicity of the Pfs48/45 With Matrix-M Vaccine, When Administered to Healthy Adult Volunteers as Assessed by Humoral Responses to the Pfs48/45 Protein

  Days 1, 29, 57, 140 and 240

• Cellular Immunogenicity of the Pfs48/45 With Matrix-M Vaccine, When Administered to Healthy Adult Volunteers as Assessed by Cellular Responses to the Pfs48/45 Protein

  Days 1, 29, 57, 140 and 240

• Ex Vivo Efficacy of the Pfs48/45 With Matrix-M Vaccine, When Administered to Healthy Adult Volunteers Using Direct Membrane Feeding Assays as Assessed by Transmission-reducing Activity

  Days 1, 29, 57, 140 and 240

• Ex Vivo Efficacy of the Pfs48/45 With Matrix-M Vaccine, When Administered to Healthy Adult Volunteers Using Direct Membrane Feeding Assays as Assessed by Transmission-blocking Activity

  Days 1, 29, 57, 140 and 240

Study Arms (3)

Group 1 - low dose

EXPERIMENTAL

8-10 volunteers receiving three doses of 10 µg Pfs48/45 in 50 µg Matrix-M on days 0, 28 and 56 via intramuscular injection (IM) in the deltoid region of the arm

Biological: Pfs48/45 in Matrix-M

Group 2 - standard dose

EXPERIMENTAL

8-10 volunteers receiving three doses of 50 µg Pfs48/45 in 50 µg Matrix-M on days 0, 28 and 56 via intramuscular injection (IM) in the deltoid region of the arm

Biological: Pfs48/45 in Matrix-M

Group 3 - fractional dose

EXPERIMENTAL

8-10 volunteers receiving two doses of 50 µg Pfs48/45 in 50 µg Matrix-M on days 0 and 28, followed by one dose of 10 µg Pfs48/45 in 50 µg Matrix-M on day 56 via intramuscular injection (IM) in the deltoid region of the arm

Biological: Pfs48/45 in Matrix-M

Interventions

Pfs48/45 in Matrix-M BIOLOGICAL

Three doses of Pfs48/45 in Matrix-M at different doses

Group 1 - low dose; Group 2 - standard dose; Group 3 - fractional dose

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult aged 18 to 45 years.
• Able and willing (in the Investigator's opinion) to comply with all study requirements.
• Willing to allow the Investigators to discuss the volunteer's medical history with their GP.
• Volunteers with the potential to become pregnant only: must practice continuous effective contraception for the duration of the study (see section 10.10).
• Agreement to refrain from blood donation for the duration of the study.
• Able and willing to provide written informed consent to participate in the trial

You may not qualify if:

• History of clinical malaria (any species).
• Travel to a clearly malaria endemic locality during the study period or within the preceding six months.
• Use of immunoglobulins or blood products (e.g., blood transfusion) in the last three months.
• Receipt of any vaccine in the 30 days preceding enrolment, or planned receipt of any other vaccine within 30 days following each study vaccination, with the exception of COVID-19 vaccines, which should not be received between 14 days before to 7 days after any study vaccination.
• Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period.
• Concurrent involvement in another clinical trial or planned involvement during the study period.
• Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data, as assessed by the Investigator.
• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed).
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Any history of anaphylaxis in reaction to vaccinations.
• Pregnancy, lactation or intention to become pregnant during the study.
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
• History of serious psychiatric condition that may affect participation in the study.
• Any other serious chronic illness requiring hospital specialist supervision.
• Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 25 standard UK units every week.

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

CCVTM, Churchill Hospital, University of Oxford

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Interventions

Matrix-M

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Angela M Minassian
• Organization: University of Oxford

angela.minassian@bioch.ox.ac.uk

01865611424

Study Officials

• Angela M Minassian, DPhil FRCP

  Center for Clinical Vaccinology and Tropical Medicine, University of Oxford

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2022
• First Posted: June 2, 2022
• Study Start: November 2, 2022
• Primary Completion: October 19, 2023
• Study Completion: October 19, 2023
• Last Updated: March 28, 2025
• Results First Posted: March 28, 2025

Record last verified: 2023-05

Locations

GB (1)