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RECRUITINGPhase 2INTERVENTIONAL

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

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

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.

Who May Be Eligible (Plain English)

Who May Qualify: 1. Age:\>/= 9 years old and \</= 50 years old. 2. Provides written willing to sign a consent form if \>/=18 years of age. 3. Provides written willing to sign a consent form 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. Who Should NOT Join This Trial: 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). ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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.

Treatments Being Tested

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.

Locations (1)

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