Malaria Challenge in Healthy Volunteers

NCT01500980 | Completed Phase 1 DMC

• 1 other identifier: MC-003
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if sterile, protective immunity to malaria can be induced by malaria parasite exposure limited to the early liver stage of the parasite lifecycle.

Conditions

Malaria

Keywords

malaria; challenge; P. falciparum; prevention

Outcome Measures

Primary Outcomes (3)

• Microscopic evaluation of peripheral blood smears

  Detection for evidence of patent parasitemia and time to parasitemia following challenge with homologous P. falciparum sporozoites in subjects with confirmed exposure to P. falciparum sporozoites and early liver stage parasites only

  Up to 182 days

• qRT-PCR

  qRT-PCR evaluation for detection of subpatent parasitemia following a single episode of ITV

  Up to 182 days

• Number of subjects with adverse events

  Occurrence of solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs) during the study period

  up to 182 days

Secondary Outcomes (3)

• ELISA

  up to 182 days

• IFN-y ELISPOT

  up to 182 days

• ICS assay

  up to 182 days

Study Arms (5)

Pilot Phase

EXPERIMENTAL

Pilot phase will include 6 subjects and will investigate the timing of PQ dosing relative to parasite exposure.

Biological: P. falciparum infection; Drug: Chloroquine; Drug: Primaquine

Chloroquine, ITV, primaquine, malaria challenge

EXPERIMENTAL

Biological: P. falciparum infection; Drug: Chloroquine; Drug: Primaquine

Sporozoite negative vaccine

ACTIVE COMPARATOR

Drug: Chloroquine; Drug: Primaquine

Primaquine placebo

ACTIVE COMPARATOR

Biological: P. falciparum infection; Drug: Chloroquine

malaria challenge

NO INTERVENTION

Interventions

P. falciparum infection BIOLOGICAL

P. falciparum (NF54 strain) infection delivered by the bites of 12 - 15 infected A. stephensi mosquitos

Chloroquine, ITV, primaquine, malaria challenge; Pilot Phase; Primaquine placebo

Chloroquine DRUG

Weekly chloroquine dosing (600 mg loading dose, 300 mg thereafter)

Chloroquine, ITV, primaquine, malaria challenge; Pilot Phase; Primaquine placebo; Sporozoite negative vaccine

Primaquine DRUG

Primaquine (45 mg) on day 2 or 3 post ITV infection

Pilot Phase

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and non-pregnant females age 18 to 50 years
• Good general health status as demonstrated by medical history, physical exam, and screening laboratory test performed within 90 days of enrollment
• Ability and willingness to provide informed consent
• No laboratory evidence of hematologic, hepatic, or renal disease
• Assessment of Understanding questionnaire completed and passed prior to enrollment
• Reliable access to the clinical trials centers and availability to participate for duration of study
• If the subject is biologically female and of reproductive potential she must agree to consistent pregnancy prevention

You may not qualify if:

• Recent travel to a malaria endemic area within 6 months of enrollment
• Planned travel to a malaria endemic area during the study period
• History of confirmed malaria diagnosis on peripheral blood smear
• Anticipated use during the study period, or use within the following periods prior to enrollment:
• Investigational malaria vaccine at any time
• Malaria chemoprophylaxis within 6 months
• Chronic systemic immunosuppressive medications within 6 months
• Blood products or immunoglobulins within 120 days
• Investigational product or vaccine within 30 days
• Systemic antibiotics with antimalarial effects within 30 days
• Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to each ITV infection and challenge
• Medications known to interact with primaquine, chloroquine or atovaquone/proguanil (only during the study period)
• History of:
• Sickle cell disease, sickle cell trait, or other hemoglobinopathies
• Splenectomy or functional asplenia

Sponsors & Collaborators

• Seattle Children's Hospital: lead

Study Sites (1)

Seattle Biomedical Research Institute's Malaria Clinical Trials Center

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Healy SA, Murphy SC, Hume JCC, Shelton L, Kuntz S, Van Voorhis WC, Moodie Z, Metch B, Wang R, Silver-Brace T, Fishbaugher M, Kennedy M, Finney OC, Chaturvedi R, Marcsisin SR, Hobbs CV, Warner-Lubin M, Talley AK, Wong-Madden S, Stuart K, Wald A, Kappe SH, Kublin JG, Duffy PE. Chemoprophylaxis Vaccination: Phase I Study to Explore Stage-specific Immunity to Plasmodium falciparum in US Adults. Clin Infect Dis. 2020 Sep 12;71(6):1481-1490. doi: 10.1093/cid/ciz1010.

  PMID: 31621832 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Chloroquine; Primaquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Sara Healy, M.D. MPH

  Seattle Biomedical Research Institution

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2011
• First Posted: December 29, 2011
• Study Start: December 1, 2011
• Primary Completion: July 1, 2012
• Study Completion: November 1, 2012
• Last Updated: December 13, 2012

Record last verified: 2012-12

Locations

US (1)