Pfs230D1 + R21 in Matrix-M1 in African School Children and Adults

NCT07147400 | Recruiting Phase 2 DMC

• 1 other identifier: VIMT 002
• Study Type: interventional
• Target: 1,200
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 2, randomized, double-blind, controlled study designed to evaluate the safety, tolerability, immunogenicity, vaccine efficacy, and functional activity of Pfs230D1-CRM197 conjugate vaccine with R21 nanoparticle vaccine formulated on Matrix-M1. Participants (9-50 years of age) will be drawn from Bancoumana, Mali and the surrounding areas.

Conditions

Prevention of Malaria Transmission and Clinical Malaria

Outcome Measures

Primary Outcomes (8)

• Number of Participants with Immediate adverse events in all participants

  Occurrence of immediate adverse events

  Up to 30-minutes following each dose

• Number of Participants with solicited local adverse events in reactogenicity group

  Occurrence of solicited local adverse events

  Up to 7 days following each dose

• Number of Participants with Solicited systemic adverse events in reactogenicity group

  Occurrence of solicited systemic adverse events

  Up to 7 days following each dose

• Number of Participants with Unsolicited adverse events in all participants

  Occurrence of unsolicited adverse events

  Up to 28 days following each vaccination

• Number of Participants with Serious adverse events in all participants

  Occurrence of serious adverse events

  Through the whole study duration, 24 months post dose 3 or 12 months post dose 4

• Number of Participants with Abnormal Laboratory Values post-vaccination in laboratory safety group

  Laboratory adverse events

  at 7 days following each vaccination

• Anti-NANP IgG antibodies

  Antibody responses to NANP IgG antibodies

  at 4 weeks post dose 3

• Anti-Pfs230D1 IgG antibodies

  Antibody responses to Pfs230D1 IgG antibodies

  at 4 weeks post dose 3

Secondary Outcomes (5)

• To assess vaccine functional activity against transmission by DSF

  from 2 weeks to 24 weeks after completion of the primary vaccine course +/- booster

• To assess vaccine functional activity against transmission by DSF

  from 2 weeks to 24 weeks after completion of the primary vaccine course +/- booster

• humoral immunogenicity time trends and durability

  at baseline, 28 days after each dose and through study completion, at an average of 1 month

• humoral immunogenicity time trends and durability

  at baseline, 28 days after each dose and through study completion, at an average of 1 month

• To assess the protective efficacy against clinical malaria caused by Pf

  At 24 and 52 weeks after completion of the primary and booster vaccine course

Study Arms (10)

Arm 1a (n=180), 9-17 years of age, Immunobridging cohort

EXPERIMENTAL

10µg of R21 with 50µg Matrix-M1

Biological: 10µg of R21 with 50µg Matrix-M1

Arm 2a (n=180), 9-17 years of age, Immunobridging cohort

EXPERIMENTAL

Control vaccine (rabies vaccine)

Biological: RABIVAX-S

Arm 3a (n=90), 9-17 years of age, Immunobridging cohort

EXPERIMENTAL

6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation

Biological: 6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation

Arm 4a (n=90), 9-17 years of age, Immunobridging cohort

EXPERIMENTAL

6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 bedside mix

Biological: Conjugated Pfs230D1 Vaccine (Pfs230D1-CRM197) For Bedside Mixing; Biological: R21 Malaria Vaccine (Recombinant) For Bedside Mixing; Biological: MATRIX-M1 (Adjuvant) For Bedside Mixing

Arm 1b (n=120), 9-17 years of age, main cohort

EXPERIMENTAL

10µg of R21 with 50µg Matrix-M1

Biological: 10µg of R21 with 50µg Matrix-M1

Arm 2b (n=120), 9-17 years of age, main cohort

EXPERIMENTAL

Control vaccine (rabies vaccine)

Biological: RABIVAX-S

Arm 3b (n=120), 9-17 years of age, main cohort

EXPERIMENTAL

6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation

Biological: 6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation

Arm 1c (n=100), 18-50 years of age, main cohort

EXPERIMENTAL

10µg of R21 with 50µg Matrix-M1

Biological: 10µg of R21 with 50µg Matrix-M1

Arm 2c (n=100), 18-50 years of age, main cohort

EXPERIMENTAL

Control vaccine (rabies vaccine)

Biological: RABIVAX-S

Arm 3c (n=100), 18-50 years of age, main cohort

EXPERIMENTAL

6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation

Biological: 6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation

Interventions

10µg of R21 with 50µg Matrix-M1 BIOLOGICAL

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. Matrix-M1 (Adjuvanted) is cGMP manufactured by Serum Institute of India, PVD, LTD (SIIPL), Pune.

Arm 1a (n=180), 9-17 years of age, Immunobridging cohort; Arm 1b (n=120), 9-17 years of age, main cohort; Arm 1c (n=100), 18-50 years of age, main cohort

6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation BIOLOGICAL

R21 Malaria antigen is expressed in a recombinant high expressing Hansenula polymorpha production strain. The R21 Malaria drug substance lots/batches were cGMP manufactured at SIIPL, India. Recombinant CRM197 is a recombinant protein, and its drug substance lots/batches cGMP manufactured using Pseudomonas fluorescens production strain at SIIPL, India. Recombinant Pfs230D1M drug substance lots/batches of cGMP were manufactured using Hansenula Polymorpha and manufactured at the SIIPL. A single vial coformulation containing 10µg R21 and 6µg Pfs230D1-CRM197 conjugate mixed with 50µg Matrix-M1 has been developed and is manufactured by SIIPL.

Arm 3a (n=90), 9-17 years of age, Immunobridging cohort; Arm 3b (n=120), 9-17 years of age, main cohort; Arm 3c (n=100), 18-50 years of age, main cohort

RABIVAX-S BIOLOGICAL

Sterile, purified inactivated rabies vaccine prepared on vero cells, indicated for the prevention of rabies in children and adults.

Arm 2a (n=180), 9-17 years of age, Immunobridging cohort; Arm 2b (n=120), 9-17 years of age, main cohort; Arm 2c (n=100), 18-50 years of age, main cohort

Conjugated Pfs230D1 Vaccine (Pfs230D1-CRM197) For Bedside Mixing BIOLOGICAL

Recombinant Pfs230D1M drug substance lots/batches cGMP manufactured using Pichia pastoris manufactured at the Pilot Bioproduction Facility, Walter Reed Army Institute of Research (Silver Spring, Maryland), and at SIIPL respectively. Recombinant CRM197 is a recombinant protein and its drug substance lots/batches cGMP manufactured using Pseudomonas fluorescens production strain at SIIPL, India.

Arm 4a (n=90), 9-17 years of age, Immunobridging cohort

R21 Malaria Vaccine (Recombinant) For Bedside Mixing BIOLOGICAL

R21 is a fusion protein of hepatitis B surface antigen (HBsAg) to the C-terminus and central repeats of the circumsporozoite (CS) protein of Plasmodium falciparum. R21 VLP, recombinant HBsAg spontaneously self-assembled \& formed a virus-like particle, wherein circumsporozoite protein (CSP) from Plasmodium falciparum is presented on the VLP of recombinant HBsAg particles. R21 Malaria antigen expressed in recombinant high expressing Hansenula polymorpha production strain. The R21 Malaria drug substance lots/batches were cGMP manufactured at SIIPL, India.

Arm 4a (n=90), 9-17 years of age, Immunobridging cohort

MATRIX-M1 (Adjuvant) For Bedside Mixing BIOLOGICAL

active ingredient in Matrix-M1 are saponin-based fractions. Matrix-M1 has a ratio of Matrix-A and Matrix-C of 85:15 (by weight). Both Matrix-A and Matrix-C are individual fractions (separated by chromatography) derived from extracts from the Quillaja saponaria tree. Matrix-M1 (Adjuvanted) is cGMP manufactured by Serum Institute of India, PVD, LTD (SIIPL), Pune.

Arm 4a (n=90), 9-17 years of age, Immunobridging cohort

Eligibility Criteria

• Age: 9 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age:\>/= 9 years old and \</= 50 years old.
• Provides written informed consent if \>/=18 years of age.
• Provides written informed consent of parent/guardian if \<18 years of age, with additional participant written assent obtained from children \> 12 years of age.
• Known resident or long-term resident (more than 1 year) of trial site or surrounding villages.
• Available for the duration of the trial.
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
• In good general health and without clinically significant medical history in the opinion of the investigator.
• Permission for long term storage of blood samples.
• Note: If a participant withdraws consent or at the time of study completion or end of participation wishes to withdraw permission for long term storage of blood samples, this can be requested, and sample destruction will be documented.
• Females of reproductive potential aged 12 years and above who have attained menarche and are sexually active must be willing to use reliable contraception from 21 days prior to Study Day 1 and 21 days prior to Study Day 392 (booster dose) and until 1 month after the last vaccination in primary series and after booster dose.
• A reliable method of birth control includes one of the following:
• Confirmed pharmacologic contraceptives (parenteral) delivery.
• Intrauterine or implantable device.
• Barrier methods.

You may not qualify if:

• Pregnant and breastfeeding females. Pregnant, as determined by a positive urine or serum beta human choriogonadotropin (βhCG) test.
• NOTE: Pregnancy is also a criterion for discontinuation of any further vaccine dosing
• Menstruating females less than 12 years of age. (In order to avoid cultural implications of further assessing pregnancy potential i.e. sexual activity in this age group).
• Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and comply with the study protocol at a level appropriate for the participant's age.
• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, oncologic, or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
• Current or planned participation in an investigational product study until the time period of the last required study visit under this protocol.
• Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
• History of a severe allergic reaction or anaphylaxis.
• Known:
• Severe asthma, defined as asthma that is unstable or required emergent care, urgent care, hospitalization, or intubation during the past 2 years, or that has required the use of oral or parenteral corticosteroids at any time during the past 2 years.
• Autoimmune or antibody-mediated disease including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, or autoimmune thrombocytopenia.
• Immunodeficiency.
• Seizure disorder (exception: history of simple febrile seizures).
• Asplenia or functional asplenia.
• Use of chronic (≥14 days) oral or intravenous (IV) corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e., prednisone \>10 mg/day) or immunosuppressive drugs within 30 days of enrollment.

Sponsors & Collaborators

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

Study Sites (1)

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

Bamako, Mali

RECRUITING

MeSH Terms

Interventions

Matrix-M; Adjuvants, Pharmaceutic

Intervention Hierarchy (Ancestors)

Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Central Study Contacts

Prasad S Kulkarni, MD

CONTACT

+91-20-71946820; drpsk@seruminstitute.com

Sandesh M Bharati, MD

CONTACT

+91-20-71946825; sandesh.bharati@seruminstitute.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study will be conducted with a double blind. Because there is some variation in vaccine volumes, the unblinded pharmacy team will cover all syringes (after vaccine preparation) with opaque tape to maintain blinding. The participants, the clinical staff, laboratory staff and the study team involved in study endpoint assessments will be blinded to study treatment allocation. An additional layer to be implemented to promote blinding is that designated clinical staff who administer the vaccinations will only participate in study product administration and will remain separate from the team of blinded investigators who conduct all subsequent follow-up study assessments. The pharmacy team at the study site where vaccine preparation and administration is taking place will be unblinded, and they are responsible for maintaining security of study treatment assignments.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 1200 Healthy male and non-pregnant female participants of age 9-50 years will be enrolled in VIMT002 study in Bancoumana, Mali and surrounding villages. Participants aged 9 - 17 years in the immunobridging cohort (n=540) will be randomized to one of the study arms (2:2:1:1) to receive 10µg R21 in 50µg of Matrix-M1 single vial formulation, control vaccine (RABIVAX-S), or 6µg Pfs230D1-CRM197 with 10µg R21 in 50µg of Matrix-M1 as either a bedside mixture or a single-vial coformulation. Participants in the main cohort will be randomized to one of the study arms (1:1:1) to receive 10µg R21 in 50µg of Matrix-M1, control vaccine (RABIVAX-S), or 6µg Pfs230D1-CRM197 with 10 µg R21 in 50µg of Matrix-M1 single-vial coformulation.

Study Record Dates

• First Submitted: August 12, 2025
• First Posted: August 29, 2025
• Study Start: August 22, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

MA (1)