Assessment of Safety and Immunogenicity of R21/Matrix-M™ in African Children Living With HIV

Study Overview
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Brief Summary
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A Phase Ib trial to evaluate the safety and immunogenicity of R21/Matrix-M™ in African children living with HIV

Detailed Description
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This is a Phase Ib, open-label, non-randomised, controlled trial to evaluate the safety and immunogenicity of R21/Matrix-M™ in 5-36 month old African children living with HIV. The study will be conducted in Uganda at the MRC/UVRI and LSHTM Uganda research unit with recruitment taking place in Kampala, Wakiso and Entebbe. Children aged 5-36 months will be recruited to the trial. 100 children with confirmed HIV infection will be recruited to group 1. 20 children without HIV infection will be recruited to group 2. Up to 10% variation for each group will be permitted to accommodate variation in the rate of recruitment and retention. HIV positive children will be recruited from Paediatric HIV care centres within Kampala and Wakiso districts. HIV negative children will be recruited from Entebbe hospital and primary health care centres that provide immunisation and growth monitoring services. All participants will receive 3 vaccinations of 5µg R21/50µg Matrix-M™. Participants will receive their first dose at 0 months, second dose at 1 month and third dose at 2 months. Participants will receive a booster at 14 months (12 months after their third dose). Participants will be followed up for 12 months following the primary vaccination series and one month following the booster dose. Primary objective: To assess the safety and reactogenicity profile of the malaria vaccine candidate R21/Matrix-M™ in 5-36-month old African children living with HIV Secondary objectives: To assess the humoral immunogenicity of R21/Matrix-M™ in 5-36-month-old African children, comparing children living with HIV with HIV negative children To assess the impact of vaccination on HIV reservoir To assess whether increasing age and nadir CD4 count are associated with immunogenicity of R21/Matrix-M™ in 5-36-month-old African children living with HIV Tertiary objective: To assess the immunogenicity profile of R21/Matrix-M™ in 5-36-month-old African children, comparing children living with HIV with HIV negative children This trial is funded by the Serum Institute of India Pvt Ltd.

Official Title
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A Phase Ib Trial to Evaluate the Safety and Immunogenicity of R21/Matrix-M™ in African Children Living With HIV

Conditions
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Malaria

Intervention / Treatment
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* Biological: R21/Matrix-M™


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The child must be 5-36 months of age at enrolment (i.e. up to the day of their third birthday). Group 1: The child must have HIV infection (documented positive DNA PCR) with WHO stage 1 or 2 HIV disease, whether or not they are receiving ART. Group 2: The child must not have HIV infection (absence of HIV infection must be confirmed by documented negative DNA PCR at screening). Witnessed, signed/thumb-printed informed consent, obtained from the parent(s)/guardian(s) of the child Parents/guardians of the child are able and willing to comply with the requirements of the protocol, in the opinion of the investigator The child must be a permanent resident of the study area and likely to remain resident for the duration of the trial. Exclusion Criteria: Previous receipt of a malaria vaccine. Enrolment in another malaria intervention trial that could interfere with the results of this study. History of severe allergic disease or reactions, including anaphylaxis or angioedema History of allergic disease or reactions likely to be exacerbated by any component of the study vaccines, or history of allergic reactions to previous vaccinations Clinically significant laboratory abnormality as judged by the study clinician including haemoglobin of ≤8.0 g/dL . Major congenital defects. Receipt of blood transfusion, immunoglobulins and/or any blood products within the three months preceding enrolment Malnutrition requiring hospital admission at the time of enrolment. HIV disease of stage 3 or 4, as defined by the WHO clinical staging [23] Confirmed or suspected immunosuppressive or immunodeficient state (other than due to HIV infection). o This may include asplenia, use of immunosuppressant medication within the past 6 months (except for topical steroids or short-term oral steroids (course lasting <14 days). Autoimmune conditions (except mild psoriasis, well-controlled autoimmune thyroid disease, vitiligo or stable coeliac disease) Any other clinically significant disease or disorder, or social situation, elicited in medical history, physical examination or laboratory tests that, in the opinion of the study clinician, may: Put the participants at risk because of participation in the trial, or Influence the result of the trial, or Affect the participant's ability to participate in the trial These may include: diseases or disorders of the pulmonary, cardiovascular, gastrointestinal, endocrine, neurological, skin, hepatic or renal systems, cancer, bleeding disorders, abnormalities of screening laboratory tests or examinations Receipt of an investigational drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period. Current participation in another clinical trial if likely to affect data interpretation of this trial

Ages Eligible for Study
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Minimum Age: 5 Months
Maximum Age: 36 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a Phase Ib, open-label, non-randomised, controlled trial. 100 children with confirmed HIV infection will be recruited to group 1. 20 children without HIV infection will be recruited to group 2. All children will receive R21/Matrix-M™
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 - children with HIV<br>100 5-36 month old children with confirmed HIV infection. | Biological: R21/Matrix-M™<br>* Adjuvanted malaria vaccine<br>|
| Experimental: Group 2 - children without HIV<br>20 5-36 month old children without HIV infection. | Biological: R21/Matrix-M™<br>* Adjuvanted malaria vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Solicited local signs and symptoms | Occurrence of solicited local signs and symptoms | 7 days following receipt of each dose | 
| Solicited systemic signs and symptoms | Occurrence of solicited systemic signs and symptoms | 7 days following receipt of each dose | 
| SAEs | Occurrence of SAEs | Through study completion - on average for 15 months | 
| Unsolicited AEs | Occurrence of unsolicited adverse events | 30 days following receipt of each dose | 
| Clinically significant change from baseline for safety laboratory measures | Clinically significant change from baseline for safety laboratory measures | Through study completion - on average for 15 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody responses to CSP and HBsAb | Antibody responses to CSP (total anti-IgG responses to NANP and C-term region of CSP) and HBsAb | 1 and 6 months following third dose, and 1 month following booster dose | 
| HIV viral load | Change in total HIV DNA copies per million CD4+ T cells | 1 week post doses 1, 2 and booster 4 weeks following receipt of each dose | 
| CD4+ count, age at enrolment and vaccine immune response | CD4+ count, age at enrolment and vaccine immune response | 1 week after doses 1 and booster, 1 and 6 months after dose 3 and 1 month after the booster dose |