Dose-Escalating Study of Pfs230D1 in Combination With R21 in Matrix-M in African Adults

Phase 1 Randomized, Double-blind Dose-Escalating Study of Pfs230D1 in Combination With R21 in Matrix-M in Healthy African Adults

This is a Phase 1, individually randomized, double-blind, dose escalating study designed to evaluate the safety, tolerability, and immunogenicity of Pfs230D1 conjugate vaccines, R21 nanoparticle vaccine, or their combination conjugate vaccines, formulated on Matrix-M in healthy African adults aged 18 to 50 years.

Study Overview

• Status: Completed
• Conditions: Prevention of Malaria Transmission and Clinical Malaria
• Intervention / Treatment: Biological: R21; Biological: Pfs230D1-CRM197; Other: Matrix-M; Biological: Pfs230D1-EPA

Detailed Description

240 healthy adults (18-50 years of age) will be enrolled from Mali, Africa in a staggered manner by increasing Pfs230D1 dosing.

Participants will be randomized by cohorts as (detailed below) to one of the study arms to receive single antigen (Pfs230D1 or R21) or combination (Pfs230D1 + R21) with 50 μg of Matrix-M, all administered as an IM injection on a 1, 29, 57-day schedule. Participants will be followed for safety for 6 months post last dose with continued assessment for clinical malaria cases and immunogenicity up until 12 months post last dose.

Cohort 1 (n=120); 1:1:1:1:1:1

• Arm 1a (n=20): 6μg Pfs230D1-CRM197 + 5μg of R21 in 50μg Matrix-M
• Arm 1b (n=20): 6μg Pfs230D1-CRM197 + 10μg of R21 in 50μg Matrix-M
• Arm 1c (n=20): 12μg Pfs230D1-CRM197 + 5μg of R21 in 50μg Matrix-M
• Arm 1d (n=20): 12μg Pfs230D1-CRM197 + 10μg of R21 in 50μg Matrix-M
• Arm 1e (n=20): 5μg of R21 in 50μg Matrix-M
• Arm 1f (n=20): 10μg of R21 in 50μg Matrix-M

Followed by Cohort 2 (n=80); 1:1:1:1

• Arm 2a (n=20): 20μg Pfs230D1-CRM197 + 5μg of R21 in 50μg Matrix-M
• Arm 2b (n=20): 20μg Pfs230D1-CRM197 + 10μg of R21 in 50μg Matrix-M
• Arm 2c (n=20): 20μg Pfs230D1-CRM197 in 50μg Matrix-M
• Arm 2d (n=20): 20μg Pfs230D1-EPA + 5μg of R21 in 50μg Matrix-M

Followed by Cohort 3 (n=40); 1:1

• Arm 3a (n=20): 40μg Pfs230D1-CRM197 + 5μg of R21 in 50μg Matrix-M
• Arm 3b (n=20): 40μg Pfs230D1-CRM197 + 10μg of R21 in 50μg Matrix-M

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 1

Contacts and Locations

Study Locations

• Mali
  • Bamako, Mali
    • University of Science, Technique and Technology of Bamako (Usttb)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Age: 18 to 50 years old.
2. Provides written informed consent.
3. Able to understand and comply with planned study procedures and be available for the duration of the trial.
4. In good general health and without clinically significant medical history in the opinion of the investigator.
5. Females of childbearing potential must be willing to use reliable contraception from 21 days prior to Study Day 1 and until 1 month after the last vaccination.

Exclusion Criteria:

1. Pregnant and breastfeeding females.
2. Hemoglobin, white blood cell (WBC), absolute neutrophil count, or platelet levels outside the local laboratory-defined reference ranges.
3. Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined upper limit of reference range.
4. Infected with HIV, hepatitis B, hepatitis C.
5. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies.
6. Current or planned participation in an investigational product study until the time period of the last required study visit under this protocol.
7. Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
8. History of a severe allergic reaction or anaphylaxis.
9. Known: Severe asthma, Autoimmune or antibody-mediated disease, Immunodeficiency, Seizure disorder, Asplenia or functional asplenia, Use of chronic oral or intravenous corticosteroids (excluding topical or nasal), Sickle cell disease.
10. Any other condition that in the opinion of the investigator might jeopardize the safety or rights of a subject participating in the trial, interfere with the evaluation of the study objectives, or might render the subject unable to comply with the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1a (n=20); 6μg Pfs230D1-CRM197 + 5μg of R21 in 50μg Matrix-M	Biological: R21; R21 is a portion of Pf circumsporozoite protein fused with hepatitis B surface antigen in the form of non-infectious virus-like particles (VLPs) produced in yeast cells (Hansenula) by recombinant DNA technology.; Biological: Pfs230D1-CRM197; Recombinant Pfs230 domain 1 (Pfs230D1; a subdomain of a surface antigen of gametocytes, gametes, and zygotes, in the mosquito stage of Pf conjugated to CRM197 and adjuvanted with 50μg of Matrix-M.; Other: Matrix-M; Vaccine adjuvant that contains purified saponin (from Quillaja saponaria Molina) and cholesterol and phosphatidyl choline. Matrix-M will be used at a 50μg dose for vaccinations.
Experimental: Arm 1b (n=20); 6μg Pfs230D1-CRM197 + 10μg of R21 in 50μg Matrix-M	Biological: R21; R21 is a portion of Pf circumsporozoite protein fused with hepatitis B surface antigen in the form of non-infectious virus-like particles (VLPs) produced in yeast cells (Hansenula) by recombinant DNA technology.; Biological: Pfs230D1-CRM197; Recombinant Pfs230 domain 1 (Pfs230D1; a subdomain of a surface antigen of gametocytes, gametes, and zygotes, in the mosquito stage of Pf conjugated to CRM197 and adjuvanted with 50μg of Matrix-M.; Other: Matrix-M; Vaccine adjuvant that contains purified saponin (from Quillaja saponaria Molina) and cholesterol and phosphatidyl choline. Matrix-M will be used at a 50μg dose for vaccinations.
Experimental: Arm 1c (n=20); 12μg Pfs230D1-CRM197 + 5μg of R21 in 50μg Matrix-M	Biological: R21; R21 is a portion of Pf circumsporozoite protein fused with hepatitis B surface antigen in the form of non-infectious virus-like particles (VLPs) produced in yeast cells (Hansenula) by recombinant DNA technology.; Biological: Pfs230D1-CRM197; Recombinant Pfs230 domain 1 (Pfs230D1; a subdomain of a surface antigen of gametocytes, gametes, and zygotes, in the mosquito stage of Pf conjugated to CRM197 and adjuvanted with 50μg of Matrix-M.; Other: Matrix-M; Vaccine adjuvant that contains purified saponin (from Quillaja saponaria Molina) and cholesterol and phosphatidyl choline. Matrix-M will be used at a 50μg dose for vaccinations.
Experimental: Arm 1d (n=20); 12μg Pfs230D1-CRM197 + 10μg of R21 in 50μg Matrix-M	Biological: R21; R21 is a portion of Pf circumsporozoite protein fused with hepatitis B surface antigen in the form of non-infectious virus-like particles (VLPs) produced in yeast cells (Hansenula) by recombinant DNA technology.; Biological: Pfs230D1-CRM197; Recombinant Pfs230 domain 1 (Pfs230D1; a subdomain of a surface antigen of gametocytes, gametes, and zygotes, in the mosquito stage of Pf conjugated to CRM197 and adjuvanted with 50μg of Matrix-M.; Other: Matrix-M; Vaccine adjuvant that contains purified saponin (from Quillaja saponaria Molina) and cholesterol and phosphatidyl choline. Matrix-M will be used at a 50μg dose for vaccinations.
Active Comparator: Arm 1e (n=20); 5μg of R21 in 50μg Matrix-M	Biological: R21; R21 is a portion of Pf circumsporozoite protein fused with hepatitis B surface antigen in the form of non-infectious virus-like particles (VLPs) produced in yeast cells (Hansenula) by recombinant DNA technology.; Other: Matrix-M; Vaccine adjuvant that contains purified saponin (from Quillaja saponaria Molina) and cholesterol and phosphatidyl choline. Matrix-M will be used at a 50μg dose for vaccinations.
Active Comparator: Arm 1f (n=20); 10μg of R21 in 50μg Matrix-M	Biological: R21; R21 is a portion of Pf circumsporozoite protein fused with hepatitis B surface antigen in the form of non-infectious virus-like particles (VLPs) produced in yeast cells (Hansenula) by recombinant DNA technology.; Other: Matrix-M; Vaccine adjuvant that contains purified saponin (from Quillaja saponaria Molina) and cholesterol and phosphatidyl choline. Matrix-M will be used at a 50μg dose for vaccinations.
Experimental: Arm 2a (n=20); 20μg Pfs230D1-CRM197 + 5μg of R21 in 50μg Matrix-M	Biological: R21; R21 is a portion of Pf circumsporozoite protein fused with hepatitis B surface antigen in the form of non-infectious virus-like particles (VLPs) produced in yeast cells (Hansenula) by recombinant DNA technology.; Biological: Pfs230D1-CRM197; Recombinant Pfs230 domain 1 (Pfs230D1; a subdomain of a surface antigen of gametocytes, gametes, and zygotes, in the mosquito stage of Pf conjugated to CRM197 and adjuvanted with 50μg of Matrix-M.; Other: Matrix-M; Vaccine adjuvant that contains purified saponin (from Quillaja saponaria Molina) and cholesterol and phosphatidyl choline. Matrix-M will be used at a 50μg dose for vaccinations.
Experimental: Arm 2b (n=20); 20μg Pfs230D1-CRM197 + 10μg of R21 in 50μg Matrix-M	Biological: R21; R21 is a portion of Pf circumsporozoite protein fused with hepatitis B surface antigen in the form of non-infectious virus-like particles (VLPs) produced in yeast cells (Hansenula) by recombinant DNA technology.; Biological: Pfs230D1-CRM197; Recombinant Pfs230 domain 1 (Pfs230D1; a subdomain of a surface antigen of gametocytes, gametes, and zygotes, in the mosquito stage of Pf conjugated to CRM197 and adjuvanted with 50μg of Matrix-M.; Other: Matrix-M; Vaccine adjuvant that contains purified saponin (from Quillaja saponaria Molina) and cholesterol and phosphatidyl choline. Matrix-M will be used at a 50μg dose for vaccinations.
Experimental: Arm 2c (n=20); 20μg Pfs230D1-CRM197 in 50μg Matrix-M	Biological: Pfs230D1-CRM197; Recombinant Pfs230 domain 1 (Pfs230D1; a subdomain of a surface antigen of gametocytes, gametes, and zygotes, in the mosquito stage of Pf conjugated to CRM197 and adjuvanted with 50μg of Matrix-M.; Other: Matrix-M; Vaccine adjuvant that contains purified saponin (from Quillaja saponaria Molina) and cholesterol and phosphatidyl choline. Matrix-M will be used at a 50μg dose for vaccinations.
Experimental: Arm 2d (n=20); 20μg Pfs230D1-EPA + 5μg of R21 in 50μg Matrix-M	Biological: R21; R21 is a portion of Pf circumsporozoite protein fused with hepatitis B surface antigen in the form of non-infectious virus-like particles (VLPs) produced in yeast cells (Hansenula) by recombinant DNA technology.; Other: Matrix-M; Vaccine adjuvant that contains purified saponin (from Quillaja saponaria Molina) and cholesterol and phosphatidyl choline. Matrix-M will be used at a 50μg dose for vaccinations.; Biological: Pfs230D1-EPA; Recombinant Pfs230D1 conjugated to a recombinant Pseudomonas aeruginosa ExoProtein A (EPA)
Experimental: Arm 3a (n=20); 40μg Pfs230D1-CRM197 + 5μg of R21 in 50μg Matrix-M	Biological: R21; R21 is a portion of Pf circumsporozoite protein fused with hepatitis B surface antigen in the form of non-infectious virus-like particles (VLPs) produced in yeast cells (Hansenula) by recombinant DNA technology.; Biological: Pfs230D1-CRM197; Recombinant Pfs230 domain 1 (Pfs230D1; a subdomain of a surface antigen of gametocytes, gametes, and zygotes, in the mosquito stage of Pf conjugated to CRM197 and adjuvanted with 50μg of Matrix-M.; Other: Matrix-M; Vaccine adjuvant that contains purified saponin (from Quillaja saponaria Molina) and cholesterol and phosphatidyl choline. Matrix-M will be used at a 50μg dose for vaccinations.
Experimental: Arm 3b (n=20); 40μg Pfs230D1-CRM197 + 10μg of R21 in 50μg Matrix-M	Biological: R21; R21 is a portion of Pf circumsporozoite protein fused with hepatitis B surface antigen in the form of non-infectious virus-like particles (VLPs) produced in yeast cells (Hansenula) by recombinant DNA technology.; Biological: Pfs230D1-CRM197; Recombinant Pfs230 domain 1 (Pfs230D1; a subdomain of a surface antigen of gametocytes, gametes, and zygotes, in the mosquito stage of Pf conjugated to CRM197 and adjuvanted with 50μg of Matrix-M.; Other: Matrix-M; Vaccine adjuvant that contains purified saponin (from Quillaja saponaria Molina) and cholesterol and phosphatidyl choline. Matrix-M will be used at a 50μg dose for vaccinations.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Immediate adverse events	Occurrence of immediate adverse events	within 30-minutes following each dose
Number of Participants with Solicited local adverse events	Occurrence of solicited local adverse events	for 7 days following each dose
Number of Participants with Solicited systemic adverse events	Occurrence of solicited systemic adverse events	for 7 days following each dose
Number of Participants with Unsolicited adverse events	Occurrence of all unsolicited adverse events	for 28 days following each dose
Number of Participants with Abnormal Laboratory Values post-vaccination	Any significant change from baseline for laboratory values defined as adverse events	within 7 days following each dose
Number of Participants with Serious adverse events	Occurrence of serious adverse events	Till 6 months post last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-NANP IgG antibodies	Comparison of anti-NANP IgG antibodies	at 2 weeks post dose 3 in all treatment arms
Anti-Pfs230D1 IgG antibodies	Comparison of Anti-Pfs230D1 IgG antibodies	at 2 weeks post dose 3 in all treatment arms

Collaborators and Investigators

• Sponsor: Serum Institute of India Pvt. Ltd.
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)

Study record dates

Study Major Dates

• Study Start (Actual): August 30, 2024
• Primary Completion (Actual): January 24, 2026
• Study Completion (Actual): January 24, 2026

Study Registration Dates

• First Submitted: July 4, 2024
• First Submitted That Met QC Criteria: July 11, 2024
• First Posted (Actual): July 18, 2024

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 6, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Malaria; Matrix-M; R21 monoclonal antibody
• Other Study ID Numbers: VIMT 001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No