Safety and Immunogenicity of SUM-101 Malaria Vaccine in Children and Infants Living in Burkina Faso

A Phase 1b, Randomised, Controlled Age De-escalation, Dose-finding Study to Evaluate the Safety, Reactogenicity and Immunogenicity of Full-length MSP1/GLA-SE (SUM-101) Malaria Vaccine in Healthy Young Children, and Infants in Burkina Faso.

This clinical trial aims to learn about the safety and immunogenicity of the blood-stage malaria vaccine candidate SUM-101 in infants and children, paving the way for its incorporation into a multi-stage malaria vaccine. This will be the first time SUM-101 will be evaluated for safety and immunogenicity in infants and children. The main questions it aims to answer are:

• Are the 3 doses of full-length MSP1/GLA-SE (SUM-101) in young children and infants safe?
• Do the 3 doses of full-length MSP1/GLA-SE (SUM-101) in young children and infants produce any reactogenicity?
• How is the immunogenicity in young children and infants generated by the 3 doses of full-length MSP1/GLA-SE (SUM-101)?
• What is the optimal dose of the full-length MSP1/GLA-SE (SUM-101) in young children and infants? The study will be divided into two arms with 5 groups conducted at a single centre. In total, 69 healthy malaria-pre-exposed infants and children aged 5 months to 5 years will be enrolled in this study.

Participants will be included in one of the following groups:

• Arm 1_Group 1 (open-label design): This will be the first cohort enrolled to assess safety in children (18 months - 5 years) before the vaccination of infants commences. Therefore, all participants in Arm 1 will receive three doses of SUM-101 vaccine (25µg MSP1 + 5µg GLA-SE) on D0, D28 and D56.
• Arm 2_Group 2-5 (randomised, controlled, double-blind design): This will be the second cohort enrolled to assess safety in the target population (infants aged 5-17 months). Infants will be assigned to Groups 2-5 to enable evaluation of two doses of MSP1 (25µg and 10µg) and two doses of GLA-SE (5µg and 2.5µg). The infants in each group will be randomised into A) a vaccine arm (12 participants) and B) a control arm (3 participants). All participants in Groups 2-5 will receive three doses of either SUM-101 vaccine or Verorab® (Rabies vaccine) on D0, D28 and D56.

Participants will visit the clinic for screening and once selected for enrolment. No later than 28 days after selection participants will receive the 1st vaccination (Visit Day 0) and 2nd and 3rd Vaccination on Day 28 and Day 56. On Day 1 to 6 days post each vaccination (Day 1-6, Day 29-34 and Day 57-62) each participant will be visited at home daily by a field worker for assessment and recording of any solicited and unsolicited AEs (Reactogenicity visits).

The study will be divided into two arms conducted at a single centre. In total, 69 volunteers will be enrolled in this Phase Ib study to assess the safety, reactogenicity and immunogenicity of SUM-101 in healthy malaria pre-exposed infants and children aged 5 months to 5 years.

Arm 1_Group 1 (open-label design): This will be the first cohort enrolled to assess safety in children (18 months - 5 years) before the vaccination of infants commences. Therefore, all participants in Group 1 (n=9 with n=3 sentinels) will receive three doses of SUM-101 vaccine (25µg MSP1 + 5µg GLA-SE) on D0, D28 and D56 in an open-label design. Female and male participants will be enrolled.

Arm 2_Group 2-5 (randomised, controlled, double-blind design): This will be the second cohort enrolled to assess safety in the target population (infants aged 5-17 months). Infants will be assigned to Groups 2-5 (15 participants in each group with n=4 sentinels) to enable evaluation of two doses of MSP1 (25µg and 10µg) and two doses of GLA-SE (5µg and 2.5µg). To reduce bias, the vaccination of Groups 2-5 will be conducted in a double-blind manner. The infants in each group will be randomised into A) a vaccine arm (12 participants) and B) a control arm (3 participants). Female and male participants will be enrolled. All participants in Groups 2-5 will receive three doses of either SUM-101 vaccine or Verorab® (Rabies vaccine) on D0, D28 and D56.

Sentinel participants: The first 3 participants enrolled in Group 1 will be sentinels who will be vaccinated in an open label manner. To ensure blinding, the first 4 participants enrolled in Groups 2-5 will be sentinels who will be vaccinated with either SUM-101 or control vaccine. The sentinel participants will be vaccinated in the following order; Arm1_Group 1 sentinels: On the first day, the first participant will be enrolled and vaccinated alone and observed on the day following vaccination. If there are no safety concerns, another two participants will be enrolled and vaccinated in a sequential manner at least 48 hours after the first participant and with a minimum interval between participants of 60 min to allow monitoring of any acute events. The remaining participants will be vaccinated at least 72 hours after the third sentinel participant as long as there are no safety concerns.

Arm2_Groups 2-5 sentinels: On the first day, two participants will be enrolled and vaccinated in a sequential manner with a minimum interval between the participants of 60 min to allow monitoring of any acute events. These two vaccinated participants will then be observed on the day following vaccination. If there are no safety concerns, another two participants will be enrolled and vaccinated in a sequential manner at least 48 hours after the first participant and with a minimum interval between participants of 60 min to allow monitoring of any acute events. The remaining participants will be vaccinated at least 72 hours after the fourth sentinel participant as long as there are no safety concerns.

Inclusion Criteria:

• Resident in the study area villages and participant's parent(s)/legal guardian anticipate being available for vaccination and follow-up for following last dose of vaccination.
• Z-score of weight-for-age within ±2SD.

Exclusion Criteria:

• Clinically significant skin disorder (psoriasis, contact dermatitis etc.), immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurological illness, major congenital defects, malnutrition requiring hospital admission and anaemia.
• History of allergic reaction, significant IgE-mediated event, or anaphylaxis to immunisation.
• Clinically significant laboratory abnormality as judged by the study investigator.
• History of blood transfusion.
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.
• Previous vaccination with experimental malaria vaccines.
• Participation in another research study/clinical trial involving receipt of an investigational medicinal product or planned use during the study period.
• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection (no HIV testing); asplenia; recurrent, severe infections and chronic immunosuppressant medication (For corticosteroids, this will mean prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed).
• Any significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant´s ability to participate in the trial.