Antimalarial prophylactic efficacy of a weekly dose atovaquone-proguanil

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Tuebingen AöR

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Parasitic Diseases [C03]

Trial duration

12 Nov 2025 → ongoing

Decision date (initial)

2024-11-21

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518884-36-00

EudraCT number

2022-004145-12

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Prophylaxis, Efficacy, Safety

The overall primary objective is to evaluate the prophylactic efficacy of a weekly dose administration of oral AP 250/100 mg in non-immune healthy volunteers exposed to malaria by intravenous administration of heterologous PfSPZ Challenge (NF54).

Secondary objectives 1

1. Secondary objectives are: 1. To assess the safety and tolerability of weekly oral atovaquone-proguanil (250/100 mg) in non-immune healthy volunteers exposed to intravenous administration of PfSPZ Challenge (NF54). 2. To assess drug exposure profiles of atovaquone, proguanil and cycloguanil following weekly oral atovaquone-proguanil 250/100 mg and malaria exposure by intravenous administration of PfSPZ Challenge (NF54).

Conditions and MedDRA coding

Malaria

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. • Healthy malaria-naive adults aged 18 to 40 years.
2. • Able and willing (in the Investigator’s opinion) to comply with all study requirements
3. • Willing to allow the investigators to discuss the volunteer’s medical history with their general practitioner if required.
4. • Residence in or nearby Tübingen with a maximum travel time to our study centre of 1 hour for the study period
5. • Women who agree to practice effective contraception for the duration of the study (a method which results in a low failure rate; i.e. less than 1% per year).
6. • Weight over 40 kg and BMI ≥19 and ≤ 30.
7. • Agreement to refrain from blood donation during the course of the study and after the end of their involvement in the study according to the local and national blood banking eligibility criteria
8. • Provision of written informed consent to receive PfSPZ Challenge (NF54) for CHMI.
9. • Reachable (24/7) by mobile phone during the CHMI period.
10. • Willingness to take AP or placebo at the scheduled timepoint and a curative antimalarial regimen following CHMI and development of amplifying parasitaemia.
11. • Answer all questions on the informed consent quiz correctly.

Exclusion criteria 29

1. • History of malaria.
2. • History of travel to a malaria-endemic country within the previous 12 months.
3. • Residence in a malaria endemic area for 5 or more years continuously.
4. • Prior receipt of malaria vaccine candidates or malaria challenge products.
5. • Use of concomitant medication with anti-plasmodial activity within 30 days of study enrolment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin erythromycin, fluoroquinolones, or azithromycin).
6. • Receipt of an investigational product in the 90 days preceding, or planned receipt during the study period.
7. • Contraindication to the use of the following antimalarial medications: AP, artemether-lumefantrine, artesunate.
8. • Use of medication interacting with AP (e.g. metoclopramide, tetracycline, rifampicin, rifabutin, efavirenz, or nevirapine).
9. • Use of medication interacting with artemether-lumefantrine (e.g. disopyramide, quinidine, procainamide, amiodarone, rifampicin, carbamazepine, phenytoin, phenobarbital, haloperidol, domperidone, pimozide or pipamperone).
10. • History of seizure (except uncomplicated febrile convulsion at childhood)
11. • Pregnancy, lactation or intention to become pregnant during the study.
12. • Diagnosis of any immune deficiency disorder, including human immunodeficiency virus (HIV) infection.
13. • History of (functional) asplenia.
14. • Use of chronic (more than 14 days) systemic immunosuppressive medication within the past 2 years (topical or inhaled immunosuppressive agents are allowed).
15. • Any other confirmed or suspected immunosuppressive or immunodeficient state (e.g., repeated and/or unusual infection), including history of infection caused by opportunistic organisms, any infection or combination of infections that suggest underlying immunodeficiency, history of meningitis, encephalitis, septic shock, life-threatening soft tissue infection, more than one pneumonia.
16. • Known (or signs consistent with) sickle cell anemia, sickle cell trait, thalassemia or thalassemia trait, glucose-6-phosphate dehydrogenase deficiency.
17. • Use of immunoglobulins or blood products within 3 months prior to enrolment.
18. • History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
19. • Any other serious chronic illness requiring hospital specialist supervision
20. • History of serious psychiatric condition that may affect participation in the study
21. • Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 24 g (men) or 12 g (women) per day.
22. • Suspected or known illicit drug abuse in the 5 years preceding enrolment.
23. • Volunteers unable to be closely followed for social, geographic or psychological reasons.
24. • Any other significant disease, disorder, finding at medical history, biochemistry, haematology tests, urine analysis results, clinical examination or electrocardiogram (ECG) which, in the opinion of the Investigator, may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data.
25. • Difficulties with venepuncture for blood sampling at screening visit due to veins that easily collapse or roll, are too thin, or are hard to find.
26. • Positive for hepatitis B surface antigen (HBs-antigen).
27. • Seropositive for hepatitis C virus (antibodies to HCV).
28. • Abnormal vital signs
29. • Intake of medication that potentially interferes with the study intervention or rescue drugs

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efficacy endpoint Proportion of protected volunteers. Protection is defined as the absence of amplifying parasitaemia in the peripheral blood for +21 days following CHMI with PfSPZ Challenge (NF54) in volunteers receiving AP (250/100 mg) for chemoprophylaxis. Amplifying parasitaemia is defined as at least one qPCR result above 20 blood-stage parasites per ML followed by a second qPCR result with an at least 4-fold increased blood stage parasitaemia 24-48 hours apartPrimary safety endpoint Numbe

Secondary endpoints 1

1. Secondary safety endpoint Occurrence of any related AE from time of AP/placebo D0 until the end of the study.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Tuebingen AöR

Sponsor organisation

Universitaetsklinikum Tuebingen AöR

Address

Geissweg 3, Innenstadt Innenstadt

City

Tuebingen

Postcode

72076

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Alexandra Roth

Public contact point

Organisation

Universitaetsklinikum Tuebingen AöR

Contact name

Alexandra Roth

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications