NCT02858817

Safety and Protective Efficacy of IV Immunization With Cryopreserved PfSPZ Under A/P Chemoprophylaxis

Completed Phase 1 Last updated 15 July 2019

What this trial tests

Phase 1 trial testing atovaquone/proguanil 250mg/100mg (A/P) in Malaria in 30 participants. Completed in 16 November 2017.

Timeline

28 November 2016

Primary endpoint
16 November 2017

16 November 2017

Quick facts

Lead sponsor	University Hospital Tuebingen
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	factorial
Masking	quadruple
Primary purpose	prevention
Enrollment	30
Start date	28 November 2016
Primary completion	16 November 2017
Estimated completion	16 November 2017

Drugs / interventions tested

• atovaquone/proguanil 250mg/100mg (A/P) — full drug profile →
• PfSPZ Challenge (NF54) — full drug profile →
• NaCl 0,9% — full drug profile →

Conditions studied

• Malaria — all drugs for Malaria →

Sponsor

University Hospital Tuebingen

Who can join

Adults 18 to 45, any sex, with Malaria. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Single center, randomized, placebo-controlled, double-blinded trial using PfSPZ Challenge (NF54) under A/P chemoprophylaxis for immunization and PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8) for repeat CHMI.

A total of 30 adult, healthy, malaria naïve volunteers will receive three injections by Direct Venous Inoculation (DVI) of either placebo (n = 10), 51,200 PfSPZ Challenge (NF54) (n = 10), or 150,000 PfSPZ Challenge (NF54) (n = 10) under chemoprophylaxis with A/P at 4 week intervals. The placebo will be normal saline (0.9% NaCl).

Ten weeks after the last dose of PfSPZ Challenge (NF54) for immunization, volunteers will undergo first CHMI and followed until asexual blood stage parasitemia, detected by quantitative real time PCR (qPCR) or thick blood smear microscopy. If parasitemic, they will be treated with A/P (used in this case as a standard treatment regimen). In the event of no parasitemia, volunteers will be followed until Day 28 post-CHMI and will not receive A/P.

Sixteen to forty-four weeks after the last immunization, a second CHMI will be administered to assess longevity and cross-strain protection. All volunteers will be followed up to 28 days post-inoculation. Those developing parasitemia will be treated with A/P.

Volunteers of Group A will have CHMI with PfSPZ Challenge (NF54) followed by PfSPZ Challenge (7G8). Volunteers of Group B will have CHMI with PfSPZ Challenge (NF54) or PfSPZ Challenge (7G8) followed by PfSPZ Challenge (7G8). In the case that protective efficacy in Group A is ≥75% CHMI sequence will be 7G8-7G8. In the case that protective efficacy against homologous Challenge in Group A is \<75%, volunteers will receive the same sequence as in Group A (NF54-7G8).

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Sporozoite immunization: innovative translational science to support the fight against malaria.
   Richie TL, Church LWP, Murshedkar T, Billingsley PF, et al · · 2023 · cited 44× · PMID 37571809 · DOI 10.1080/14760584.2023.2245890
2. Expansion of Functional Myeloid-Derived Suppressor Cells in Controlled Human Malaria Infection.
   Lamsfus Calle C, Fendel R, Singh A, Richie TL, et al · · 2021 · cited 14× · PMID 33815377 · DOI 10.3389/fimmu.2021.625712
3. Complete attenuation of Plasmodium falciparum sporozoites by atovaquone-proguanil.
   Borrmann S, Sulyok Z, Müller K, Fendel R, et al · · 2025 · cited 2× · PMID 41023197 · DOI 10.1038/s44321-025-00301-8