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

Not Applicable

Not yet recruiting

• Conditions: Prevention of Malaria Transmission and Clinical Malaria
• Interventions: Biological: 10µg of R21 with 50µg Matrix-M1; Biological: RABIVAX-S; Biological: 6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation; Biological: Conjugated Pfs230D1 Vaccine (Pfs230D1-CRM197) For Bedside Mixing; Biological: R21 Malaria Vaccine (Recombinant) For Bedside Mixing; Biological: MATRIX-M1 (Adjuvant) For Bedside Mixing

• Registration Number: NCT07147400
• Lead Sponsor: Serum Institute of India Pvt. Ltd.

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.

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

Study Timeline

• Status Verified: 2025-08
• Study Start: 2025-08-01
• Study First Submitted: 2025-08-12
• Study First Submitted QC: 2025-08-28
• Last Update Submitted: 2025-08-28
• Study First Posted: 2025-08-29
• Last Update Posted: 2025-08-29
• Primary Completion: 2027-11
• Study Completion: 2027-11-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 1200

Inclusion Criteria

1. Age:>/= 9 years old and </= 50 years old.

2. Provides written informed consent if >/=18 years of age.

3. Provides written informed consent of parent/guardian if <18 years of age, with additional participant written assent obtained from children > 12 years of age.

4. Known resident or long-term resident (more than 1 year) of trial site or surrounding villages.

5. Available for the duration of the trial.

6. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.

7. In good general health and without clinically significant medical history in the opinion of the investigator.

8. 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.

9. 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.

EXCLUSION CRITERIA:

1. 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

2. 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).

   NOTE: If a female less than 12 years of age starts menarche while on study it will not be exclusionary for them to continue participation, but will undergo pregnancy testing prior to each vaccination.

3. 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.

4. 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.

5. Current or planned participation in an investigational product study until the time period of the last required study visit under this protocol.

6. Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.

7. History of a severe allergic reaction or anaphylaxis.

8. 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.
   • Hypersensitivity reaction to rabies vaccine in the past.

9. Receipt of:

   • Live vaccine within 4 weeks prior to enrollment or a killed vaccine within 2 weeks prior to enrollment.
   • Immunoglobulins and/or blood products within the past 3 months.
   • Any malaria vaccine in the past.
   • Any investigational product in the last 6 months

10. Any other condition that in the opinion of the investigator might jeopardize the safety or rights of a participant participating in the trial, interfere with the evaluation of the study objectives, or might render the participant unable to comply with the protocol.

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1a (n=180), 9-17 years of age, Immunobridging cohort	10µg of R21 with 50µg Matrix-M1	10µg of R21 with 50µg Matrix-M1
Arm 1b (n=120), 9-17 years of age, main cohort	10µg of R21 with 50µg Matrix-M1	10µg of R21 with 50µg Matrix-M1
Arm 1c (n=100), 18-50 years of age, main cohort	10µg of R21 with 50µg Matrix-M1	10µg of R21 with 50µg Matrix-M1
Arm 2c (n=100), 18-50 years of age, main cohort	RABIVAX-S	Control vaccine (rabies vaccine)
Arm 2a (n=180), 9-17 years of age, Immunobridging cohort	RABIVAX-S	Control vaccine (rabies vaccine)
Arm 3a (n=90), 9-17 years of age, Immunobridging cohort	6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation	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	Conjugated Pfs230D1 Vaccine (Pfs230D1-CRM197) For Bedside Mixing	6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 bedside mix
Arm 4a (n=90), 9-17 years of age, Immunobridging cohort	R21 Malaria Vaccine (Recombinant) For Bedside Mixing	6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 bedside mix
Arm 4a (n=90), 9-17 years of age, Immunobridging cohort	MATRIX-M1 (Adjuvant) For Bedside Mixing	6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 bedside mix
Arm 2b (n=120), 9-17 years of age, main cohort	RABIVAX-S	Control vaccine (rabies vaccine)
Arm 3b (n=120), 9-17 years of age, main cohort	6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation	6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation
Arm 3c (n=100), 18-50 years of age, main cohort	6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation	6µg of Pfs230D1-CRM197 + 10µg of R21 with 50µg Matrix-M1 single vial coformulation

Primary Outcome Measures

Name	Time	Method
Number of Participants with solicited local adverse events in reactogenicity group	Up to 7 days following each dose	Occurrence of solicited local adverse events
Number of Participants with Serious adverse events in all participants	Through the whole study duration, 24 months post dose 3 or 12 months post dose 4	Occurrence of serious adverse events
Anti-Pfs230D1 IgG antibodies	at 4 weeks post dose 3	Antibody responses to Pfs230D1 IgG antibodies
Number of Participants with Solicited systemic adverse events in reactogenicity group	Up to 7 days following each dose	Occurrence of solicited systemic adverse events
Number of Participants with Abnormal Laboratory Values post-vaccination in laboratory safety group	at 7 days following each vaccination	Laboratory adverse events
Anti-NANP IgG antibodies	at 4 weeks post dose 3	Antibody responses to NANP IgG antibodies
Number of Participants with Immediate adverse events in all participants	Up to 30-minutes following each dose	Occurrence of immediate adverse events
Number of Participants with Unsolicited adverse events in all participants	Up to 28 days following each vaccination	Occurrence of unsolicited adverse events

Secondary Outcome Measures

Name	Time	Method
humoral immunogenicity time trends and durability	at baseline, 28 days after each dose and through study completion, at an average of 1 month	Antibody responses to NANP
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	Efficacy against clinical malaria as defined by: presence of asexual P. falciparum parasitemia \>0 parasites/µL and/or RDT positive with either an axillary temperature of ≥37.5 °C or one or more of the following symptoms: history of fever within the last 48 hours, headache, myalgia, arthralgia, malaise, nausea, dizziness, or abdominal pain
To assess vaccine functional activity against transmission by DSF	from 2 weeks to 24 weeks after completion of the primary vaccine course +/- booster	Proportion reduction in DSFs with at least one infected mosquito

Trial Locations

Locations (1)

University of Science, Technique and Technology of Bamako (Usttb); 🇲🇱 Bamako, Mali