Pfs230D1 plus R21 malaria vaccines with Matrix-M1 in children and adults in Mali

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

This study will test whether adding the Pfs230D1 transmission-blocking vaccine to the R21/Matrix-M1 malaria vaccine is safe and improves immune protection in 9–50-year-olds living near Bancoumana, Mali.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 1200 (estimated)
• Ages: 9 Years to 50 Years
• Sex: All
• Sponsor: Serum Institute of India Pvt. Ltd. (Industry-sponsored)
• Drugs / interventions: prednisone
• Locations: 1 site (Bamako)
• Trial ID: NCT07147400 on ClinicalTrials.gov

What this trial studies

This Phase 2, randomized, double-blind, controlled trial compares R21/Matrix-M1 alone, a control vaccine (RABIVAX-S), and a single-vial coformulation of Pfs230D1-CRM197 with R21/Matrix-M1 in participants aged 9–50 from Bancoumana, Mali. Enrollment includes an immunobridging pediatric cohort (9–17 years) and a main cohort (9–17 and 18–50 years) with randomization to study arms and three intramuscular doses given at days 0, 28, and 56, plus an optional booster around 52 weeks. The protocol collects safety and tolerability data, measures antibody levels and functional transmission-blocking activity, and monitors clinical malaria and transmission-related endpoints. A Data and Safety Monitoring Board will review early pediatric safety data before expanding enrollment and samples are stored for longer-term analyses.

Who should consider this trial

Good fit: Ideal candidates are healthy 9–50-year-old long-term residents of the Bancoumana area who can provide required consent/assent and commit to scheduled clinic visits.

Not a fit: People outside the 9–50 age range, those with significant medical conditions or contraindications to vaccination, and those unwilling to complete follow-up are unlikely to receive benefit from participation.

Why it matters

Potential benefit: If successful, the combination could both protect vaccinated individuals from clinical malaria and reduce onward transmission by inducing transmission-blocking antibodies.

How similar studies have performed: R21 formulated with Matrix-M has shown promising protective efficacy in earlier trials and Pfs230D1 has demonstrated immunogenicity, but the combined single-vial coformulation approach is novel and not yet proven.

Eligibility criteria

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.

Where this trial is running

Bamako

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

Study contacts

• Study coordinator: Prasad S Kulkarni, MD

Conditions Prevention of Malaria Transmission and Clinical Malaria