Health TrialsbyHealthPanel

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

ConditionPrevention of Malaria Transmission and Clinical Malaria
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age9-50
SponsorSerum Institute of India Pvt. Ltd.

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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.

Disqualifiers

Pregnant and breastfeeding females. Pregnant, as determined by a positive urine or serum beta human choriogonadotropin (βhCG) test.

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • 10µg of R21 with 50µg Matrix-M1

    Biological/Vaccine

    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.

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

    Biological/Vaccine

    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.

  • RABIVAX-S

    Biological/Vaccine

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

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

    Biological/Vaccine

    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.

  • R21 Malaria Vaccine (Recombinant) For Bedside Mixing

    Biological/Vaccine

    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.

  • MATRIX-M1 (Adjuvant) For Bedside Mixing

    Biological/Vaccine

    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.

Treatment groups

1,200 Participants
are divided into 10 treatment groups

10

Treatment groups

See each treatment group below.

Group A: Arm 1a (n=180), 9-17 years of age, Immunobridging cohortExperimental treatment 1 intervention
Group B: Arm 2a (n=180), 9-17 years of age, Immunobridging cohortExperimental treatment 1 intervention
Group C: Arm 3a (n=90), 9-17 years of age, Immunobridging cohortExperimental treatment 1 intervention
Group D: Arm 4a (n=90), 9-17 years of age, Immunobridging cohortExperimental treatment 3 interventions
Group E: Arm 1b (n=120), 9-17 years of age, main cohortExperimental treatment 1 intervention
Group F: Arm 2b (n=120), 9-17 years of age, main cohortExperimental treatment 1 intervention
Group G: Arm 3b (n=120), 9-17 years of age, main cohortExperimental treatment 1 intervention
Group H: Arm 1c (n=100), 18-50 years of age, main cohortExperimental treatment 1 intervention
Group I: Arm 2c (n=100), 18-50 years of age, main cohortExperimental treatment 1 intervention
Group J: Arm 3c (n=100), 18-50 years of age, main cohortExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Number of Participants with Immediate adverse events in all participants

Occurrence of immediate adverse events

Time frame
Up to 30-minutes following each dose
2

Number of Participants with solicited local adverse events in reactogenicity group

Occurrence of solicited local adverse events

Time frame
Up to 7 days following each dose
3

Number of Participants with Solicited systemic adverse events in reactogenicity group

Occurrence of solicited systemic adverse events

Time frame
Up to 7 days following each dose
4

Number of Participants with Unsolicited adverse events in all participants

Occurrence of unsolicited adverse events

Time frame
Up to 28 days following each vaccination

Secondary outcomes

1

To assess vaccine functional activity against transmission by DSF

Proportion reduction in proportion of infected mosquitoes (among those dissected)

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

To assess vaccine functional activity against transmission by DSF

Proportion reduction in DSFs with at least one infected mosquito

Time frame
from 2 weeks to 24 weeks after completion of the primary vaccine course +/- booster
3

humoral immunogenicity time trends and durability

Antibody responses to Pfs230D1

Time frame
at baseline, 28 days after each dose and through study completion, at an average of 1 month
4

humoral immunogenicity time trends and durability

Antibody responses to NANP

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Serum Institute of India Pvt. Ltd.

Lead sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Source ClinicalTrials.gov
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