Safety of and Immune Response to a Malaria Vaccine (MSP1 42-C1) With or Without CPG 7909 Adjuvant - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	Johns Hopkins Bloomberg School of Public Health
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00320658

Purpose

The purpose of this study is to determine the safety of and immune response to a preventive malaria vaccine, MSP1 42-C1/Alhydrogel, in healthy adults. This study will also compare responses to two different doses of the malaria vaccine given with or without the adjuvant CPG 7909.

Condition	Intervention	Phase
Malaria	Biological: MSP1 42-C1/Alhydrogel Biological: CPG 7909	Phase I

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Prevention
Official Title:	Phase 1 Study of the Safety and Immunogenicity of MSP1 42-C1/Alhydrogel With and Without CPG 7909, an Asexual Blood Stage Vaccine for Plasmodium Falciparum Malaria

Resource links provided by NLM:

MedlinePlus related topics: Malaria

Drug Information available for: Aluminum hydroxide Algeldrate

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Anti-MSP1 42 antibody concentration as measured by ELISA [ Time Frame: At Day 70 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To demonstrate that the addition of CPG 7909 improves the specific immune responses to MSP142-FVO and MSP142-3D7, as compared to MSP142-C1/Alhydrogel [ Time Frame: At Day 70 ] [ Designated as safety issue: No ]
To determine the dose of MSP142-C1/Alhydrogel + CPG 7909 that generates the highest serum antibody levels of MSP142-FVO and MSP142-3D7 [ Time Frame: At Day 70 ] [ Designated as safety issue: No ]

Enrollment:	60
Study Start Date:	March 2006
Study Completion Date:	July 2007
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A 3 vaccinations with a dose of 40 mcg MSP1 42-C1/Alhydrogel given into the deltoid muscle of either arm. Each vaccination will be given 1 month apart. This arm will enroll concurrently with Arm B.	Biological: MSP1 42-C1/Alhydrogel Recombinant MSP1 42-C1/Alhydrogel vaccine (one of two doses)
Experimental: B 3 vaccinations with a dose of 40 mcg MSP1 42-C1/Alhydrogel and CPG7909 given into the deltoid muscle of either arm. Each vaccination will be given 1 month apart. This arm will enroll concurrently with Arm A.	Biological: MSP1 42-C1/Alhydrogel Recombinant MSP1 42-C1/Alhydrogel vaccine (one of two doses) Biological: CPG 7909 Adjuvant
Experimental: C 3 vaccinations with a dose of 160 mcg MSP1 42-C1/Alhydrogel given into the deltoid muscle of either arm. Each vaccination will be given 1 month apart. This arm will enroll concurrently with Arm D after review of the results from Arms A and B.	Biological: MSP1 42-C1/Alhydrogel Recombinant MSP1 42-C1/Alhydrogel vaccine (one of two doses)
Experimental: D 3 vaccinations with a dose of 160 mcg MSP1 42-C1/Alhydrogel and CPG7909 given into the deltoid muscle of either arm. Each vaccination will be given 1 month apart. This arm will enroll concurrently with Arm C after review of the results from Arms A and B.	Biological: MSP1 42-C1/Alhydrogel Recombinant MSP1 42-C1/Alhydrogel vaccine (one of two doses) Biological: CPG 7909 Adjuvant

Detailed Description:

In 2002, the World Health Organization reported a worldwide malaria incidence of approximately 300 million clinical cases annually, with approximately 1 million deaths attributed to malaria alone or in combination with other diseases. The parasite Plasmodium falciparum is responsible for the majority of these infections and deaths. During P. falciparum infection, liver cells are invaded by the parasite and asexual multiplication occurs. The liver cells burst, and tens of thousands of infectious particles called merozoites are released. A multiprotein complex on the surface of a merozoite is necessary for the merozoite to infect a blood cell. MSP1 42-C1 is a malaria vaccine that mimics MSP1 42, a protein in the multiprotein complex. By introducing this "decoy" form of MSP1 42, infection of additional blood cells may be blocked. The adjuvant CPG 7909 is known to elicit cell-mediated immunity, the arm of the immune system that defends the body against intracellular pathogens such as P. falciparum. This study will evaluate the safety and immunogenicity of MSP1 42-C1/Alhydrogel at two different doses in healthy adults. The vaccine will be given either alone or with CPG 7909.

This study will last at least 34 weeks. Participants will be randomly assigned to one of four groups:

Group A participants will receive three injections of the lower dose of MSP1 42-C1/Alhydrogel.
Group B participants will receive three injections of the lower dose of MSP1 42-C1/Alhydrogel and CPG 7909.
Group C participants will receive three injections of the higher dose of MSP1 42-C1/Alhydrogel.
Group D participants will receive three injections of the higher dose of MSP1 42-C1/Alhydrogel and CPG 7909.

Enrollment into Groups C and D will begin only after safety review of all participants in Groups A and B. All participants will receive their assigned injections at study entry, Week 4, and Week 8, and will be asked to return to the clinic the day after each vaccination for clinical evaluation. Participants will be asked to keep a diary for 6 days after each vaccination, taking note of their body temperatures and any side effects they experience. There will be a total of 18 study visits over 34 weeks. A clinical evaluation will occur at each visit. Blood collection, vital signs measurement, and urine collection will occur at selected visits.

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Good general health
Willing to be followed for the duration of the study
Willing to use acceptable methods of contraception

Exclusion Criteria:

Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may affect the ability of the volunteer to understand and cooperate with the study
Liver disease (ALT greater than upper limit of normal [ULN])
Kidney disease (serum creatinine greater than ULN)
Hematologic disease (absolute neutrophil count of less than 1,500 cells/mm3; hemoglobin less than lower limit of normal, by sex; OR platelet count less than 140,000 mm3)
Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease
Participation in another investigational vaccine or drug trial within 30 days of study entry or while this study is ongoing
Active drug or alcohol abuse causing medical, occupational, or family problems during the 12 months prior to study entry
History of severe allergic reaction or anaphylaxis
HIV-1 infected
Hepatitis C virus infected
Hepatitis B surface antigen positive
Known immunodeficiency syndrome
Use of corticosteroids or immunosuppressive drugs within 30 days prior to study entry. Participants who have used topical or nasal corticosteroids are not excluded.
Live vaccine within 4 weeks prior to study entry
Killed vaccine within 2 weeks prior to study entry
Blood products within 6 months prior to study entry
Absence of spleen
Previously received an investigational malaria vaccine
Received antimalarial prophylaxis during the 12 months prior to study entry
Received chloroquine or other aminoquinolines within 12 weeks of study entry
Prior malaria infection
Known allergy to nickel
Pre-existing autoimmune or antibody-mediated disease. More information about this criterion can be found in the protocol.
Any medical, psychiatric, social, or occupational condition or other responsibility that, in the opinion of the investigator, would interfere with the study
Other condition that, in the opinion of the investigator, would affect the volunteer's participation in the study
Pregnancy or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00320658

Locations

United States, District of Columbia
Center for Immunization Research, Johns Hopkins University, Bloomberg School of Public Health
Washington, District of Columbia, United States, 20037

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Johns Hopkins Bloomberg School of Public Health

Investigators

Principal Investigator:

Anna Durbin, MD

Johns Hopkins Bloomberg School of Public Health

More Information

Publications:

Boutlis CS, Riley EM, Anstey NM, de Souza JB. Glycosylphosphatidylinositols in malaria pathogenesis and immunity: potential for therapeutic inhibition and vaccination. Curr Top Microbiol Immunol. 2005;297:145-85. Review.

Hill AV. Pre-erythrocytic malaria vaccines: towards greater efficacy. Nat Rev Immunol. 2006 Jan;6(1):21-32. Review.

Reed ZH, Friede M, Kieny MP. Malaria vaccine development: progress and challenges. Curr Mol Med. 2006 Mar;6(2):231-45.

Saul A, Lawrence G, Smillie A, Rzepczyk CM, Reed C, Taylor D, Anderson K, Stowers A, Kemp R, Allworth A, Anders RF, Brown GV, Pye D, Schoofs P, Irving DO, Dyer SL, Woodrow GC, Briggs WR, Reber R, Sturchler D. Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant. Vaccine. 1999 Aug 6;17(23-24):3145-59.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ellis RD, Martin LB, Shaffer D, Long CA, Miura K, Fay MP, Narum DL, Zhu D, Mullen GE, Mahanty S, Miller LH, Durbin AP. Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1(42)-C1/Alhydrogel with and without CPG 7909 in malaria naïve adults. PLoS One. 2010 Jan 22;5(1):e8787.

Responsible Party:	Anna Durbin, MD, Center for Immunization Research, Johns Hopkins School of Public Health
ClinicalTrials.gov Identifier:	NCT00320658 History of Changes
Obsolete Identifiers:	NCT00342420
Other Study ID Numbers:	CIR 212, NIH Protocol Number 05-I-0240, WIRB Protocol Number 20051029
Study First Received:	May 1, 2006
Last Updated:	January 18, 2008
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Plasmodium falciparum

Additional relevant MeSH terms:

Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Aluminum Hydroxide
Adjuvants, Immunologic

Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antacids
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 09, 2012