Efficacy, Immunogenicity and Safety Study of GSK Biologicals' Candidate Malaria Vaccine Evaluating Different Dose Schedules in a Sporozoite Challenge Model in Healthy Malaria-naïve Adults
NCT ID: NCT03162614
Last Updated: 2020-10-27
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
154 participants
INTERVENTIONAL
2017-05-24
2018-09-24
Brief Summary
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Detailed Description
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Note that as a result of internal change in data standards terminology, the study data collected was converted to cDISC and the statistical analysis plan was amended accordingly. "Day 0" in the study design was replaced by "Day 1"; consequently, "Day n" was replaced by "Day n+1". Thus, the timeframes (Day 0, Day n) of Outcome Measures described in this study record are different to that denoted in the full protocol document posted.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
PREVENTION
NONE
Study Groups
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AduFx Group
Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and Month 1 and 1/5th of RTS,S/AS01B full dose at Month 7, and underwent sporozoite challenge.
RTS,S/AS01B
Subjects will receive intramuscular injection of RTS,S/AS01B.
Sporozoite-infected mosquitoes challenge.
Mosquitoes infected approximately 2-3 weeks earlier that are likely to contain sporozoites in their salivary glands will be allowed to feed on the subjects. For each subject, five mosquitoes will be allowed to feed over five minutes, after which they will be dissected to confirm how many were infected, and the salivary glands scored. If required additional mosquitoes will be allowed to feed until a total of five infected mosquitoes with a minimum of 2+ salivary gland scores have fed.
The challenge occurs approximately 90 days (three months) after the last vaccination.
Subjects will be monitored during 28 days after having bitten by mosquitoes and when parasites are found in their blood, they will be treated with appropriate anti-malarial drugs.
2PedFx Group
Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01E double dose at Month 0 and Month 1, and 1/5th of double dose RTS,S/AS01E at Month 7, and underwent sporozoite challenge.
RTS,S/AS01E
Subjects will receive intramuscular injection of RTS,S/AS01E.
Sporozoite-infected mosquitoes challenge.
Mosquitoes infected approximately 2-3 weeks earlier that are likely to contain sporozoites in their salivary glands will be allowed to feed on the subjects. For each subject, five mosquitoes will be allowed to feed over five minutes, after which they will be dissected to confirm how many were infected, and the salivary glands scored. If required additional mosquitoes will be allowed to feed until a total of five infected mosquitoes with a minimum of 2+ salivary gland scores have fed.
The challenge occurs approximately 90 days (three months) after the last vaccination.
Subjects will be monitored during 28 days after having bitten by mosquitoes and when parasites are found in their blood, they will be treated with appropriate anti-malarial drugs.
PedFx Group
Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01E full dose at Month 0 and Month 1, and 1/5th of RTS,S/AS01E full dose at Month 7, and underwent sporozoite challenge.
RTS,S/AS01E
Subjects will receive intramuscular injection of RTS,S/AS01E.
Sporozoite-infected mosquitoes challenge.
Mosquitoes infected approximately 2-3 weeks earlier that are likely to contain sporozoites in their salivary glands will be allowed to feed on the subjects. For each subject, five mosquitoes will be allowed to feed over five minutes, after which they will be dissected to confirm how many were infected, and the salivary glands scored. If required additional mosquitoes will be allowed to feed until a total of five infected mosquitoes with a minimum of 2+ salivary gland scores have fed.
The challenge occurs approximately 90 days (three months) after the last vaccination.
Subjects will be monitored during 28 days after having bitten by mosquitoes and when parasites are found in their blood, they will be treated with appropriate anti-malarial drugs.
Adu2Fx Group
Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and 1/5th of RTS,S/AS01B full dose at Month 1 and Month 7, and underwent sporozoite challenge.
RTS,S/AS01B
Subjects will receive intramuscular injection of RTS,S/AS01B.
Sporozoite-infected mosquitoes challenge.
Mosquitoes infected approximately 2-3 weeks earlier that are likely to contain sporozoites in their salivary glands will be allowed to feed on the subjects. For each subject, five mosquitoes will be allowed to feed over five minutes, after which they will be dissected to confirm how many were infected, and the salivary glands scored. If required additional mosquitoes will be allowed to feed until a total of five infected mosquitoes with a minimum of 2+ salivary gland scores have fed.
The challenge occurs approximately 90 days (three months) after the last vaccination.
Subjects will be monitored during 28 days after having bitten by mosquitoes and when parasites are found in their blood, they will be treated with appropriate anti-malarial drugs.
Adu1Fx Group
Healthy subjects, between, and including, 18 and 55 years of age, who received RTS,S/AS01B full dose at Month 0 and 1/5th of RTS,S/AS01B full dose administered at Month 7, and underwent sporozoite challenge.
RTS,S/AS01B
Subjects will receive intramuscular injection of RTS,S/AS01B.
Sporozoite-infected mosquitoes challenge.
Mosquitoes infected approximately 2-3 weeks earlier that are likely to contain sporozoites in their salivary glands will be allowed to feed on the subjects. For each subject, five mosquitoes will be allowed to feed over five minutes, after which they will be dissected to confirm how many were infected, and the salivary glands scored. If required additional mosquitoes will be allowed to feed until a total of five infected mosquitoes with a minimum of 2+ salivary gland scores have fed.
The challenge occurs approximately 90 days (three months) after the last vaccination.
Subjects will be monitored during 28 days after having bitten by mosquitoes and when parasites are found in their blood, they will be treated with appropriate anti-malarial drugs.
Control Group
Healthy subjects, between, and including, 18 and 55 years of age, who did not receive any immunization but underwent sporozoite challenge.
Sporozoite-infected mosquitoes challenge.
Mosquitoes infected approximately 2-3 weeks earlier that are likely to contain sporozoites in their salivary glands will be allowed to feed on the subjects. For each subject, five mosquitoes will be allowed to feed over five minutes, after which they will be dissected to confirm how many were infected, and the salivary glands scored. If required additional mosquitoes will be allowed to feed until a total of five infected mosquitoes with a minimum of 2+ salivary gland scores have fed.
The challenge occurs approximately 90 days (three months) after the last vaccination.
Subjects will be monitored during 28 days after having bitten by mosquitoes and when parasites are found in their blood, they will be treated with appropriate anti-malarial drugs.
Interventions
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RTS,S/AS01E
Subjects will receive intramuscular injection of RTS,S/AS01E.
RTS,S/AS01B
Subjects will receive intramuscular injection of RTS,S/AS01B.
Sporozoite-infected mosquitoes challenge.
Mosquitoes infected approximately 2-3 weeks earlier that are likely to contain sporozoites in their salivary glands will be allowed to feed on the subjects. For each subject, five mosquitoes will be allowed to feed over five minutes, after which they will be dissected to confirm how many were infected, and the salivary glands scored. If required additional mosquitoes will be allowed to feed until a total of five infected mosquitoes with a minimum of 2+ salivary gland scores have fed.
The challenge occurs approximately 90 days (three months) after the last vaccination.
Subjects will be monitored during 28 days after having bitten by mosquitoes and when parasites are found in their blood, they will be treated with appropriate anti-malarial drugs.
Eligibility Criteria
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Inclusion Criteria
* Written informed consent obtained from the subject prior to performing of any study specific procedure.
* A male or female between, and including, 18 and 55 years of age at the time of enrolment.
* Healthy subjects as established by medical history and clinical examination before entering into the study.
* Available to participate for the duration of the study.
* Female subjects of non-childbearing potential may be enrolled in the study.
\- Non-childbearing potential is defined as pre-menarche, current tubal ligation, hysterectomy, ovariectomy or post-menopause.
* Female subjects of childbearing potential may be enrolled in the study, if the subject:
* has practiced adequate contraception for 30 days prior to vaccination, and
* has a negative pregnancy test at enrolment, and
* has agreed to continue adequate contraception during the entire treatment period and for two months after completion of the vaccination series and/or malaria challenge.
Exclusion Criteria
* Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.
* Chronic administration of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose. For corticosteroids, this will mean prednisone ≥ 20 mg/day, or equivalent. Inhaled and topical steroids are allowed.
* Administration of long-acting immune-modifying drugs at any time during the study period.
* Chronic use of antibiotics with antimalarial effects.
* Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting seven days before the first dose.
* Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.
* Seropositive for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
* Documented HIV-positive subject.
* Previous vaccination against malaria.
* History of malaria chemoprophylaxis within 60 days prior to vaccination.
* Any history of malaria (for the vaccine groups).
* Planned travel to malaria endemic areas during the study period.
* History of splenectomy.
* Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
* Family history of congenital or hereditary immunodeficiency.
* History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
* History of anaphylaxis post-vaccination.
* Hypersensitivity to latex.
* History of any reaction or hypersensitivity likely to be exacerbated by chloroquine.
* History of psoriasis and porphyria, which may be exacerbated after chloroquine treatment.
* Current use of medications known to cause drug reactions to chloroquine.
* History of severe reactions to mosquito bites.
* Major congenital defects.
* Serious chronic illness.
* History of any neurological disorders or seizures.
* Acute disease and/or fever at the time of enrolment. Fever is defined as temperature ≥ 37.5°C/99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C/100.4°F for rectal route.
\- Subjects with a minor illness without fever may be enrolled at the discretion of the investigator.
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.
* Any abnormal baseline laboratory screening tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, hemoglobin, platelet count, total white blood cells (WBC), out of normal range as defined in the protocol.
* Evidence of increased cardiovascular disease risk, "moderate" or "high", according to the National health and nutrition examination survey I criteria.
* Hepatomegaly, right upper quadrant abdominal pain or tenderness.
* Personal history of autoimmune disease.
* Administration of immunoglobulins and/or any blood products during the period starting three months before the first dose of study vaccine or planned administration during the study period.
* Pregnant or lactating female.
* History of chronic alcohol consumption and/or drug abuse.
* Female planning to become pregnant or planning to discontinue contraceptive precautions.
* History of blood donation within 56 days preceding enrolment.
* Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study.
18 Years
55 Years
ALL
Yes
Sponsors
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The PATH Malaria Vaccine Initiative (MVI)
OTHER
GlaxoSmithKline
INDUSTRY
Responsible Party
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Principal Investigators
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GSK Clinical Trials
Role: STUDY_DIRECTOR
GlaxoSmithKline
Locations
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GSK Investigational Site
Silver Spring, Maryland, United States
Countries
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References
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James E. Moon, Christian Ockenhouse, Jason A. Regules, Johan Vekemans, Cynthia Lee, Ilin Chuang, Magali Traskine, Erik Jongert, Karen Ivinson, Danielle Morelle, Jack L. Komisar, Marc Lievens, Martha Sedegah, Lindsey Garver, April K. Sikaffy, Norman C. Waters, William Ripley Ballou, Opokua Ofori-Anyinam for the RTS,S Malaria Vaccine Working Group. CLI_092_A Phase IIa Controlled Human Malaria Infection and Immunogenicity Study of RTS,S/AS01E and RTS,S/AS01B Delayed Fractional Dose Regimens in Malaria-Naïve Adults. J Infect Dis. 2020 Jul 20;jiaa421. doi: 10.1093/infdis/jiaa421. Online ahead of print.
Spreng RL, Seaton KE, Lin L, Hilliard S, Horn GQ, Abraha M, Deal AW, Li K, Carnacchi AJ, Feeney E, Shabbir S, Zhang L, Bekker V, Mudrak SV, Dutta S, Mercer LD, Gregory S, King CR, Wille-Reece U, Jongert E, Kisalu NK, Tomaras GD, Dennison SM. Identification of RTS,S/AS01 vaccine-induced humoral biomarkers predictive of protection against controlled human malaria infection. JCI Insight. 2024 Oct 8;9(19):e178801. doi: 10.1172/jci.insight.178801.
Moon JE, Ockenhouse C, Regules JA, Vekemans J, Lee C, Chuang I, Traskine M, Jongert E, Ivinson K, Morelle D, Komisar JL, Lievens M, Sedegah M, Garver LS, Sikaffy AK, Waters NC, Ballou WR, Ofori-Anyinam O; RTS,S Malaria Vaccine Working Group. A Phase IIa Controlled Human Malaria Infection and Immunogenicity Study of RTS,S/AS01E and RTS,S/AS01B Delayed Fractional Dose Regimens in Malaria-Naive Adults. J Infect Dis. 2020 Oct 13;222(10):1681-1691. doi: 10.1093/infdis/jiaa421.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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205081
Identifier Type: -
Identifier Source: org_study_id