Monoclonal antibodies to prevent post-discharge malaria in children with severe anaemia or severe malaria

Single-Use Antimalarial Monoclonal Antibodies for Post-Discharge Malaria Prevention in Children With Severe Anaemia or Severe Malaria in Kenya: A Multi-Centre, Parallel-Group, Two-Arm Randomised Placebo-Controlled Non-Inferiority Trial

This trial will test whether giving monoclonal antibodies to children hospitalized with severe anaemia or severe malaria can prevent malaria after they leave the hospital.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 398 (estimated)
• Ages: N/A to 9 Years
• Sex: All
• Sponsor: Liverpool School of Tropical Medicine (other)
• Locations: 2 sites (Kisumu, Nyanza and 1 other locations)
• Trial ID: NCT07082205 on ClinicalTrials.gov

What this trial studies

This phase 3 randomized interventional trial enrolls children under 10 hospitalized with severe anaemia or severe malaria in western Kenya to test whether monoclonal antibodies given after discharge reduce subsequent malaria and hospital readmissions. Participants are screened in hospital and must be clinically stable with post-transfusion haemoglobin ≥5.0 g/dl before randomization to receive either long-acting antimalarial monoclonal antibodies or placebo, with comparison arms receiving standard post-discharge chemoprevention (monthly dihydroartemisinin–piperaquine) or placebo PDMC. The monoclonal antibodies target a conserved circumsporozoite protein epitope to neutralize Plasmodium falciparum and could provide longer protection than the three-month PDMC regimen. Primary outcomes include post-discharge malaria incidence, readmission, and safety over the high-risk follow-up period.

Who should consider this trial

Good fit: Children under 10 who were hospitalized with severe anaemia or severe malaria, reside in the study catchment area, are clinically stable with post-transfusion haemoglobin ≥5.0 g/dl, and whose parent/guardian provides consent are ideal candidates.

Not a fit: Children who live outside malaria-endemic areas, remain clinically unstable at discharge, have insufficient post-transfusion haemoglobin, or meet exclusion criteria (including inability to take oral medication or lack of consent) are unlikely to benefit from this intervention.

Why it matters

Potential benefit: If successful, the monoclonal antibodies could provide longer-lasting protection after discharge, reducing malaria-related readmissions and deaths.

How similar studies have performed: Post-discharge malaria chemoprevention has been very effective in clinical trials, and monoclonal antibodies targeting the CSP epitope have shown protective activity in earlier studies, but using mAbs specifically for post-discharge prevention is a newer application now being tested in phase 3.

Eligibility criteria

Inclusion Criteria:

Inclusion criteria for enrolment into the pre-study screening period

* Aged \<10 years of both sexes
* Severe anaemia or severe malaria: Initially hospitalised with haemoglobin \<5.0 g/dl or PCV \<15%, or requirement for blood transfusion for other clinical reasons on or during admission to the hospital, or severe malaria, defined as a requirement for parenteral artesunate in the opinion of the treating clinician and the presence of microscopy or RDT confirmed Plasmodium infection
* Resident in catchment area

Eligibility criteria for enrolment

* Fulfilled the pre-study screening eligibility criteria
* Post-transfusion haemoglobin \>=5.0 g/dl or PCV \>=15%
* Clinically stable, able to take oral medication, able to feed (for breastfeeding children) or eat (for older children) and able to sit unaided (for older children who were already able to do so before hospitalisation)
* Provision of informed consent by parent or guardian Exclusion criteria for enrolment into the pre-study screening period

Exclusion Criteria:

Exclusion criteria for enrolment into the pre-study screening period

* Recognised specific other causes of severe anaemia (i.e., trauma, haematological malignancy, known bleeding disorders, such as haemophilia)
* Sickle cell anaemia/sickle cell disease
* Body weight \<5 kg
* HIV infection or on daily cotrimoxazole prophylaxis

Exclusion criteria for enrolment

* Previous enrolment in the present study
* Children who are scheduled to receive any of the four doses of the malaria vaccine within 6 months after enrolment.
* Received any RTS,S or R21 malaria vaccine primary series or booster dose within the last 14 days inclusive
* On or eligible for cotrimoxazole prophylaxis for HIV infection or HIV exposure
* Children with sickle cell disease because they are eligible for daily proguanil
* Known hypersensitivity to artemether-lumefantrine or dihydroartemisinin-piperaquine
* Anticipated to reside for more than 1 month of the 6-month (26 weeks) intervention period outside of the catchment area (e.g. boarding school)
* Use or known need at enrolment for concomitant prohibited medication during the first 6 months post-discharge
* Ongoing or planned participation in another clinical trial involving ongoing or scheduled treatment with prohibited medicinal products or active follow-up during the first 26 weeks post-discharge
* A known need at the time of enrolment for scheduled surgery during the first 6 months post-discharge
* Suspected non-compliance with the follow-up schedule and protocol in the opinion of the investigator
* Known heart conditions or family history of congenital prolongation of the QTc interval, or taking medicinal products that are known to prolong the QTc interval

Where this trial is running

Kisumu, Nyanza and 1 other locations

• HomaBay County Teaching and Referral Hospital — Kisumu, Nyanza, Kenya (RECRUITING)
• Siaya County Referral Hospital — Kisumu, Nyanza, Kenya (RECRUITING)

Study contacts

• Principal investigator: Feiko O Ter Kuile, MD, PhD — Liverpool School of Tropical Medicine
• Study coordinator: Mary I Otiti, BSc. MBChB, MSc.

Conditions: Malaria, Severe Malaria, Severe Anaemia, Post Discharge, monoclonal antibodies, malaria, post-discharge, prevention