NCT07147400

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

Phase 2 Randomized, Double-blind, Controlled Study of Pfs230D1-CRM197 With R21 in Matrix-M1 in Healthy African School Children and Adults

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 1,200 (estimated)
• Sponsor: Serum Institute of India Pvt. Ltd. · Industry
• Sex: All
• Age: 9 Years – 50 Years
• Healthy volunteers: Accepted

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.

Detailed description

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 alone in 50μg of Matrix-M1, 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 who are aged 9-17 years will be randomized to one of the study arms (1:1:1) to receive 10μg R21 alone 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. Enrollment of participants aged 9-17 years in the main cohort will be done after DSMB reviews the 7-day safety data post dose 1 from the immunobridging cohort. Participants in the main cohort who are aged 18 - 50 years will be randomized to one of the study arms (1:1:1) to receive either 10μg R21 alone in 50μg of Matrix-M1, control vaccine (RABIVAX-S), or 6μg Pfs230D1-CRM197 with 10μg R21 in 50μg of Matrix-M1 single-vial coformulation. Enrollment of adult participants aged 18 -50 years in the main cohort (n=300) will be done from the start of the study and will be independent of enrollment into of the pediatric cohort (9-17 years). All vaccines will be administered as an intramuscular (IM) injection on a 0, 28, 56 day schedule with an option for additional follow-up for a subsequent malaria transmission season with or without a fourth dose approximately 52 weeks after the third vaccine dose (based on year 1 results). Initial enrollment will be staggered over time for safety, but all participants will be analyzed together for primary, secondary, and exploratory endpoints. A total 1200 participants will be randomized into the study as below: Immunobridging cohort (Participants 9-17 years of age, n = 540) (2:2:1:1 randomization) * Arm 1a (n = 180): 10µg of R21 with 50µg Matrix-M1 on study day 0, 28, 56 +/- 392 * Arm 2a (n = 180): Control vaccine (rabies vaccine) on study day 0, 28, 56 +/- 392 * Arm 3a (n = 90): 6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation on study day 0, 28, 56 +/- 392 * Arm 4a (n = 90): 6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 bedside mix on study day 0, 28, 56 +/- 392 Main cohort: Participants 9-17 years of age (n = 360) (1:1:1 randomization): * Arm 1b (n=120): 10µg of R21 with 50µg Matrix-M1 on study day 0, 28, 56 +/- 392 * Arm 2b (n = 120): Control vaccine (rabies vaccine) on study day 0, 28, 56 +/- 392 * Arm 3b (n = 120): 6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation on study day 0, 28, 56 +/- 392 Participants 18-50 years of age (n = 300) (1:1:1 randomization): * Arm 1c (n=100): 10µg of R21 with 50µg Matrix-M1 on study day 0, 28, 56 +/- 392 * Arm 2c (n = 100): Control vaccine (rabies vaccine) on study day 0, 28, 56 +/- 392 * Arm 3c (n = 100): 6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation on study day 0, 28, 56 +/- 392

Conditions

• Prevention of Malaria Transmission and Clinical Malaria

Interventions

Type	Name	Description
BIOLOGICAL	10µg of R21 with 50µg Matrix-M1	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.
BIOLOGICAL	6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation	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.
BIOLOGICAL	RABIVAX-S	Sterile, purified inactivated rabies vaccine prepared on vero cells, indicated for the prevention of rabies in children and adults.
BIOLOGICAL	Conjugated Pfs230D1 Vaccine (Pfs230D1-CRM197) For Bedside Mixing	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.
BIOLOGICAL	R21 Malaria Vaccine (Recombinant) For Bedside Mixing	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.
BIOLOGICAL	MATRIX-M1 (Adjuvant) For Bedside Mixing	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.

Timeline

• Start date: 2025-08-22
• Primary completion: 2027-11-01
• Completion: 2027-11-01
• First posted: 2025-08-29
• Last updated: 2025-11-19

Locations

1 site across 1 country: Mali