Optimization of Controlled Human Malarial Infection by Injection of P. Falciparum Sporozoites in Non-Immune Adults

NCT01771848 | Completed Phase 1 DMC

• 1 other identifier: BACHMI-01
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 2

Brief Summary

The study is designed to establish the best dose to safely infect healthy individuals with Plasmodium falciparum sporozoites (PfSPZ) by injection. The goal of this study is to achieve infections in human volunteers with infection rates of 100% and pre-patent periods of less than 12 days.

Conditions

Malaria

Keywords

Malaria; Plasmodium falciparum

Outcome Measures

Primary Outcomes (1)

• Infectivity of the administration regimens

  For each trial stage (A and B) the infectivity of the three administration regimens will be assessed by thick film microscopy and q-PCR for P. falciparum DNA. The time from parasite inoculation to first detection of blood stage parasitemia will be assessed by thick blood film microscopy.

  Study day 6 to day 90 post challenge

Secondary Outcomes (1)

• Safety of PfSPZ Challenge

  All study visits until day 90 post challenge

Other Outcomes (3)

• Parasite multiplication rates using qPCR for P. falciparum DNA

  Samples taken at pre-determined timepoints upto 8 months

• Cellular and humoral immune responses against parasites

  Samples taken at pre-determined timepoints upto 8 months

• Stage specific expression patterns of parasite genes

  Samples taken at pre-determined timepoints upto 8 months

Study Arms (6)

Grp 1-10ul x 2; 2,500 PfSPZ Challenge-Part A

EXPERIMENTAL

PART A: Group 1 (n=6): 2,500 PfSPZ administered IM in a volume of 10 µL in 2 sites (one injection of 10µL containing 1,250 PfSPZ in each deltoid).

Biological: PfSPZ Challenge

Grp 2-50ul x 2; 2,500 PfSPZ Challenge-Part A

EXPERIMENTAL

PART A: Group 2 (n=6): 2,500 PfSPZ administered IM in a volume of 50 µL in 2 sites (one injection of 50µL containing 1,250 PfSPZ in each deltoid).

Biological: PfSPZ Challenge

Grp 3-250ul x 2; 2,500 PfSPZ Challenge-Part A

EXPERIMENTAL

PART A: Group 3 (n=6): 2,500 PfSPZ administered IM in a volume of 250 µL in 2 sites (one injection of 250 µL containing 1,250 PfSPZ in each deltoid).

Biological: PfSPZ Challenge

Grp 4-50ul x 2; 25,000 PfSPZ Challenge, Part B

EXPERIMENTAL

PART B: BEGINS AFTER COMPLETION OF PART A Group 4 (n=6) (control group) 25,000 PfSPZ administered IM in a volume of 50 µL in 2 sites (one injection of 50 µL containing 12,500 PfSPZ in each deltoid).

Biological: PfSPZ Challenge

Grp 5-Optimal vol Part A x 2; 25,000 PfSPZ Challenge, Part B

EXPERIMENTAL

PART B: BEGINS AFTER COMPLETION OF PART A Group 5 (n=6) 25,000 PfSPZ administered IM in the optimum volume determined in Part A in 2 sites (one injection of the optimum volume containing 12,500 PfSPZ in each deltoid). If the optimal volume in Part A is 50µL, then Group 5 will be modified to avoid duplication of regimens between groups 4 and 5. In this case, volunteers in group 5 will be administered a dose of 25,000 PfSPZ administered intradermally in four 10 µL injections. (Every volunteer will receive 4 ID injections of 6,250 PfSPZ in a volume of 10 µL each, with 2 injections in each arm respectively).

Biological: PfSPZ Challenge

Grp 6-Optimal vol Part A x 2; 125,000* PfSPZ Challenge, Part B

EXPERIMENTAL

PART B: BEGINS AFTER COMPLETION OF PART A Group 6 (n=6) 125,000 PfSPZ administered IM in the optimum volume determined in Part A in 2 sites (one injection of the optimum volume containing 62,500 PfSPZ in each deltoid) if the volume is 50 µL or 250 µL. \*If the optimal volume in Part A is 10 µL, then Group 6 will receive 100,000 PfSPZ (2 inoculations of 50,000 PfSPZ) instead of 125,000 PfSPZ.

Biological: PfSPZ Challenge

Interventions

PfSPZ Challenge BIOLOGICAL

Aseptic, purified, vialed, cryopreserved fully infectious NF54 P. falciparum sporozoites

Grp 1-10ul x 2; 2,500 PfSPZ Challenge-Part A; Grp 2-50ul x 2; 2,500 PfSPZ Challenge-Part A; Grp 3-250ul x 2; 2,500 PfSPZ Challenge-Part A; Grp 4-50ul x 2; 25,000 PfSPZ Challenge, Part B; Grp 5-Optimal vol Part A x 2; 25,000 PfSPZ Challenge, Part B; Grp 6-Optimal vol Part A x 2; 125,000* PfSPZ Challenge, Part B

Eligibility Criteria

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

You may qualify if:

• Healthy adults aged 18 to 45 years
• Able and willing (in the Investigator's opinion) to comply with all study requirements
• Women only: must agree to practice continuous effective contraception for the duration of the study (such as hormonal contraceptives, condom or intrauterine device (IUD)).
• Agreement to refrain from blood donation in Spain during the course of the study and thereafter
• Agree not to participate in another study with an investigational product during the course of this study
• Written informed consent to undergo CHMI
• Reachable (24/7) by mobile phone during the whole study period
• Willingness to take a curative anti-malarial regimen
• Agreement to stay overnight for observation during the period of intensive follow-up post-challenge if required
• Answer all questions on the informed consent quiz correctly
• A body mass index \< 35

You may not qualify if:

• History of P. falciparum malaria
• Travel to malaria endemic region before the participation in the study 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, or azithromycin)
• Is using and intends to continuing using a medication known to cause drug reactions with chloroquine or Malarone®, such as cimetidine, metoclopramide, antacids or kaolin (antacids and kaolin can be administered at least 4 hours from intake of chloroquine)
• Receipt of an investigational product in the 30 days preceding enrolment, 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 enrolment
• Presence 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
• Contraindications or known allergy to the first-line anti-malarial medications: chloroquine, atovaquone/proguanil and artemether/lumefantrine.
• History of cancer (except successfully treated and cured 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

Sponsors & Collaborators

• Sanaria Inc.: lead
• Barcelona Centre for International Health Research: collaborator

Study Sites (2)

Centre d'Investigació del Medicament Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Barcelona, 08025, Spain

Location

CRESIB, Hospital Clínic-Universitat de Barcelona

Barcelona, 08036, Spain

Location

Related Publications (5)

• Mordmuller B, Supan C, Sim KL, Gomez-Perez GP, Ospina Salazar CL, Held J, Bolte S, Esen M, Tschan S, Joanny F, Lamsfus Calle C, Lohr SJ, Lalremruata A, Gunasekera A, James ER, Billingsley PF, Richman A, Chakravarty S, Legarda A, Munoz J, Antonijoan RM, Ballester MR, Hoffman SL, Alonso PL, Kremsner PG. Direct venous inoculation of Plasmodium falciparum sporozoites for controlled human malaria infection: a dose-finding trial in two centres. Malar J. 2015 Mar 18;14:117. doi: 10.1186/s12936-015-0628-0.

  PMID: 25889522 BACKGROUND

• Shekalaghe S, Rutaihwa M, Billingsley PF, Chemba M, Daubenberger CA, James ER, Mpina M, Ali Juma O, Schindler T, Huber E, Gunasekera A, Manoj A, Simon B, Saverino E, Church LWP, Hermsen CC, Sauerwein RW, Plowe C, Venkatesan M, Sasi P, Lweno O, Mutani P, Hamad A, Mohammed A, Urassa A, Mzee T, Padilla D, Ruben A, Sim BKL, Tanner M, Abdulla S, Hoffman SL. Controlled human malaria infection of Tanzanians by intradermal injection of aseptic, purified, cryopreserved Plasmodium falciparum sporozoites. Am J Trop Med Hyg. 2014 Sep;91(3):471-480. doi: 10.4269/ajtmh.14-0119. Epub 2014 Jul 28.

  PMID: 25070995 BACKGROUND

• Roestenberg M, Bijker EM, Sim BKL, Billingsley PF, James ER, Bastiaens GJH, Teirlinck AC, Scholzen A, Teelen K, Arens T, van der Ven AJAM, Gunasekera A, Chakravarty S, Velmurugan S, Hermsen CC, Sauerwein RW, Hoffman SL. Controlled human malaria infections by intradermal injection of cryopreserved Plasmodium falciparum sporozoites. Am J Trop Med Hyg. 2013 Jan;88(1):5-13. doi: 10.4269/ajtmh.2012.12-0613. Epub 2012 Nov 13.

  PMID: 23149582 BACKGROUND

• 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 BACKGROUND

• Gomez-Perez GP, Legarda A, Munoz J, Sim BK, Ballester MR, Dobano C, Moncunill G, Campo JJ, Cistero P, Jimenez A, Barrios D, Mordmuller B, Pardos J, Navarro M, Zita CJ, Nhamuave CA, Garcia-Basteiro AL, Sanz A, Aldea M, Manoj A, Gunasekera A, Billingsley PF, Aponte JJ, James ER, Guinovart C, Antonijoan RM, Kremsner PG, Hoffman SL, Alonso PL. Controlled human malaria infection by intramuscular and direct venous inoculation of cryopreserved Plasmodium falciparum sporozoites in malaria-naive volunteers: effect of injection volume and dose on infectivity rates. Malar J. 2015 Aug 7;14:306. doi: 10.1186/s12936-015-0817-x.

  PMID: 26245196 RESULT

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Pedro L Alonso, MD, Ph.D.

  Barcelona Centre for International Health Research (CRESIB), Hospital Clínic-Universitat de Barcelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2013
• First Posted: January 18, 2013
• Study Start: December 1, 2012
• Primary Completion: May 1, 2013
• Study Completion: July 1, 2013
• Last Updated: April 4, 2016

Record last verified: 2016-03

Locations

ES (2)