Optimisation of Controlled Human Malaria Infection Using Sporozoites Administered by Needle and Syringe

NCT01465048 | Completed Results DMC

• 1 other identifier: VAC049
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open label, human pilot study to optimise controlled human malaria infection (CHMI) administered by Plasmodium falciparum sporozoites (PfSPZ. Volunteers will be inoculated with PfSPZ Challenge. The route of administration and dose will vary in order to identify the optimal regimen that achieves the greatest infection rate in volunteers with Plasmodium falciparum. All volunteers recruited will be healthy adults aged between 18 and 45 years. Safety and infectivity data will be collected for each of the regimens.

Conditions

Malaria; Plasmodium Falciparum

Keywords

Malaria; Protozoan Infections; Parasitic Diseases; Malaria Challenge

Outcome Measures

Primary Outcomes (1)

• Number of Participants Infected

  To determine the infectivity rates of PfSPZ Challenge administered in various regimens by thick film microscopy and highly sensitive PCR for Plasmodium falciparum DNA.

  21 days post administration of PfSPZ Challenge

Secondary Outcomes (2)

• Frequency, Incidence and Nature of Adverse Events and Serious Adverse Events Arising.

  Participants will be followed for the duration of the study, an expected average of 3 months

• Dynamics of Plasmodium Falciparum Parasite Growth Following PfSPZ Challenge Administered in Various Regimens

  21 days post administration of PfSPZ Challenge

Study Arms (3)

Plasmodium falciparum sporozoites 2sites

EXPERIMENTAL

2,500 sporozoites intradermally

Biological: Plasmodium falciparum sporozoites 2sites

Plasmodium falciparum sporozoites 1 site

EXPERIMENTAL

2,500 sporozoites intramuscularly

Biological: Plasmodium falciparum sporozoites 1 site

Plasmodium falciparum sporozoites 1site

EXPERIMENTAL

25,000 sporozoites intramuscularly

Biological: Plasmodium falciparum sporozoites 1site

Interventions

Plasmodium falciparum sporozoites 2sites BIOLOGICAL

Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 2,500 sporozoites, 50ulx2, 2 intradermal injection sites

Plasmodium falciparum sporozoites 2sites

Plasmodium falciparum sporozoites 1 site BIOLOGICAL

Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 2,500 sporozoites, 50ulx2, 2 intramuscular injection sites

Plasmodium falciparum sporozoites 1 site

Plasmodium falciparum sporozoites 1site BIOLOGICAL

Aseptic, purified, cryopreserved Plasmodium falciparum sporozoites, 25,000 sporozoites, 50ulx2, 2 intramuscular injection sites

Plasmodium falciparum sporozoites 1site

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women only: Must practice continuous effective contraception for the duration of the study.
• Agreement to refrain from blood donation during the course of the study and for at least 3 years after the end of their involvement in the study.
• Written informed consent to undergo CHMI.
• Reachable (24/7) by mobile phone during the whole study period.
• Willingness to take a curative anti-malaria regimen.
• For volunteers not living in Oxford: agreement to stay in a hotel room close to the trial centre during a part of the study (At least Day 6.5 post inoculation until 2 days after treatment commenced).
• Answer all questions on the informed consent quiz correctly.

You may not qualify if:

• History of clinical P. falciparum malaria.
• Travel to a malaria endemic region during the study period or within the preceding six months with positive P. falciparum serology at screening.
• Use of systemic antibiotics with known antimalarial activity within 30 days of study enrolment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones and azithromycin)
• Receipt of an investigational product in the 30 days preceding enrollment, or planned receipt during the study period.
• Prior receipt of an investigational malaria vaccine.
• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed).
• Use of immunoglobulins or blood products within 3 months prior to enrollment.
• History of sickle cell anemia, sickle cell trait, thalassemia or thalassemia trait.
• Pregnancy, lactation or intention to become pregnant during the study
• A history of allergic disease or reactions likely to be exacerbated by malaria infection.
• Contraindications to the use of all three proposed anti-malarial medications; Malarone, Riamet and Chloroquine.
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ).
• History of serious psychiatric condition that may affect participation in the study.
• Any other serious chronic illness requiring hospital specialist supervision.
• Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week.

Sponsors & Collaborators

• University of Oxford: lead
• Sanaria Inc.: collaborator

Study Sites (1)

Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital

Oxford, OX3 7LJ, United Kingdom

Location

Related Publications (4)

• Mukhopadhyay ES, Bellamy DG, Tinto H, Hamaluba M, Truby A, Salman AM, Hill AVS. Naturally acquired immune responses to alpha-gal in malaria endemic settings and pre-clinical efficacy testing with R21/MM. Vaccine. 2025 Dec 5;68:127897. doi: 10.1016/j.vaccine.2025.127897. Epub 2025 Nov 1.

  PMID: 41176969 DERIVED

• Longley RJ, Halbroth BR, Salman AM, Ewer KJ, Hodgson SH, Janse CJ, Khan SM, Hill AVS, Spencer AJ. Assessment of the Plasmodium falciparum Preerythrocytic Antigen UIS3 as a Potential Candidate for a Malaria Vaccine. Infect Immun. 2017 Feb 23;85(3):e00641-16. doi: 10.1128/IAI.00641-16. Print 2017 Mar.

  PMID: 28031267 DERIVED

• Hodgson SH, Llewellyn D, Silk SE, Milne KH, Elias SC, Miura K, Kamuyu G, Juma EA, Magiri C, Muia A, Jin J, Spencer AJ, Longley RJ, Mercier T, Decosterd L, Long CA, Osier FH, Hoffman SL, Ogutu B, Hill AV, Marsh K, Draper SJ. Changes in Serological Immunology Measures in UK and Kenyan Adults Post-controlled Human Malaria Infection. Front Microbiol. 2016 Oct 13;7:1604. doi: 10.3389/fmicb.2016.01604. eCollection 2016.

  PMID: 27790201 DERIVED

• Sheehy SH, Spencer AJ, Douglas AD, Sim BK, Longley RJ, Edwards NJ, Poulton ID, Kimani D, Williams AR, Anagnostou NA, Roberts R, Kerridge S, Voysey M, James ER, Billingsley PF, Gunasekera A, Lawrie AM, Hoffman SL, Hill AV. Optimising Controlled Human Malaria Infection Studies Using Cryopreserved P. falciparum Parasites Administered by Needle and Syringe. PLoS One. 2013 Jun 18;8(6):e65960. doi: 10.1371/journal.pone.0065960. Print 2013.

  PMID: 23823332 DERIVED

MeSH Terms

Conditions

Malaria; Malaria, Falciparum; Protozoan Infections; Parasitic Diseases

Condition Hierarchy (Ancestors)

Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Results Point of Contact

• Title: Dr Susanne Sheehy
• Organization: University of Oxford

susanne.sheehy@balliol.ox.ac.uk

Study Officials

• Adrian VS Hill, DPhil FRCP

  University of Oxford

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2011
• First Posted: November 4, 2011
• Study Start: October 1, 2011
• Primary Completion: February 1, 2012
• Study Completion: February 1, 2013
• Last Updated: June 24, 2013
• Results First Posted: May 28, 2013

Record last verified: 2013-06

Locations

GB (1)