NMRC-M3V-Ad-PfCA Vaccine - Clinical Trial 1

NCT ID: NCT00392015

Last Updated: 2021-05-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-12
• Study Completion Date: 2017-09-25

Brief Summary

The purpose of this study is to determine whether a new investigational malaria vaccine is safe, well tolerated and effective against experimental exposure to malaria when given to healthy people with no previous exposure to malaria. The vaccine consists of a modified form of a relatively common virus, adenovirus, that has been rendered incapable of replicating itself and modified to deliver the malaria gene of interest to the body's cells allowing the cell to manufacture the protein encoded by the gene and present it to the body's immune system in a more natural and presumably effective way.

Detailed Description

The vaccine, called NMRC-M3V-Ad-PfCA (key: NMRC + Multi-antigen Multi-stage, Malaria Vaccine + Adenovectored + P. falciparum CSP & AMA1 antigens), is a combination of two recombinant adenovirus-derived constructs (adenovectors), one expressing the pre-erythrocytic stage antigen circumsporozoite protein (CSP) and the other expressing the erythrocytic stage antigen Apical Membrane Antigen 1 (AMA1), both from the 3D7 strain of P. falciparum. The vector is an attenuated, replication-deficient adenovirus derived from wildtype serotype 5 adenovirus through the deletion of several genes. The vaccine is formulated in a buffered saline solution (Final Formulation Buffer = FFB).

This is a Phase 1/2a, randomized, open-label, dose-escalating trial of the NMRC-M3V-Ad-PfCA vaccine administered intramuscularly to healthy, malaria-naïve adult volunteers. All volunteers will be seronegative (< 1:500, by a luciferase-based neutralizing antibody assay; VRC, Bethesda) for adenovirus serotype 5. In the first part of the study (dose-escalation phase, Part A), 1 x 10^10 particle units (pu) per construct or 2 x 10^10 pu total will be administered to six volunteers as a single dose to assess safety, and 4 weeks later, 5 x 10^10 pu per construct or 1 x 10^11 pu total dose (five-fold dose escalation) will be administered to six additional volunteers. In the second part of the study (regimen-comparison phase, Part B), three regimens for administration will be compared: one dose, two doses administered ten days apart, and two doses administered 16 weeks apart. Separate groups will receive one dose of the individual components of the vaccine (NMRC-MV-Ad-PfC and NMRC-MV-Ad-PfA). Following immunization, volunteers participating in the regimen-comparison phase as well as several non-immunized control volunteers (serving as infectivity controls) will be challenged with P. falciparum sporozoites in order to assess vaccine efficacy against non-immunized controls challenged at the same time. The proposed design of the regimen-comparison phase will provide information to direct selection of an appropriate dosing regimen for subsequent studies, and will also indicate whether the two constituent antigens, when co-formulated, act synergistically, independently, or interfere with each other in the induction of antigen-specific immune responses and protective immunity.

Conditions

Plasmodium Falciparum

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Dose-escalation

NMRC-M3V-Ad-PfCA

Group Type: EXPERIMENTAL

NMRC-M3V-Ad-PfCA

Intervention Type: BIOLOGICAL

Malaria Vaccine

Regimen-comparison

NMRC-MV-Ad-PfC, NMRC-M3V-Ad-PfCA

Group Type: EXPERIMENTAL

NMRC-MV-Ad-PfC, NMRC-M3V-Ad-PfCA

Intervention Type: BIOLOGICAL

Malaria Vaccines

Interventions

NMRC-M3V-Ad-PfCA

Malaria Vaccine

Intervention Type: BIOLOGICAL

NMRC-MV-Ad-PfC, NMRC-M3V-Ad-PfCA

Malaria Vaccines

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Between the ages of 18-50 (inclusive)
• Negative results of HIV ELISA, HbSAg, anti-HCV antibody, and no other clinically significant abnormal laboratory results from screening.
• Adenovirus serotype 5 (Ad5) titer <1:500
• Able to provide written informed consent.
• Complete an Assessment of Understanding and verbalize an understanding of any questions answered incorrectly.
• In good general health without clinically significant medical history or physical exam abnormalities at screening.
• Willing to continue immunogenicity and clinical follow-ups for one year and telephone or mail (electronic/U.S. Postal) contact as long term safety monitoring provision for an additional four years (totaling five years of participation; immunized volunteers only).
• Male and female participants being immunized and female participants being challenged agree to use effective means of birth control (an FDA approved contraceptive, abstinence) between screening and 60 days following last clinical study visit or able to provide evidence of no reproductive capability.

Exclusion Criteria

• Have a history of malaria infection, exposure to malaria infection(i.e. you have been to an area that has malaria within the past two years),lived in a country with malaria for more than 5 years or receipt of certain candidate malaria vaccines
• Known immune system disease
• Known blood, heart, liver, kidney disease
• At known significant risk for developing heart disease
• A positive result on HIV testing at screening
• A positive result on Hepatitis B or C testing at screening
• Removal of your spleen
• Taking medication that suppresses the immune system within 30 days of immunization.
• Received or will be receiving another vaccine within 30 days of immunization
• Received blood products (e.g. transfused with blood cells, platelets, plasma or serum) within 120 days of the immunization
• Have had serious adverse reactions to other vaccines including hives, anaphylaxis, respiratory difficulty, tongue/mouth/neck/throat/body swelling or abdominal pain
• Pregnant, breastfeeding, or planning to become pregnant during the next year
• Plan to participate (or have participated in the last 30 days) in any other research study including an investigational drug or device
• Unwilling or unable to participate/complete all study elements
• Evidence of previous infection with adenovirus 5 or prior receipt of an adenovirus containing vaccine.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

United States Agency for International Development (USAID)

FED

Sponsor Role: collaborator

Congressionally Directed Medical Research Programs

FED

Sponsor Role: collaborator

Military Infectious Diseases Research Program (MIDRP)

NETWORK

Sponsor Role: collaborator

Naval Medical Research Center

FED

Sponsor Role: collaborator

U.S. Army Medical Research and Development Command

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Cindy Tamminga, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Naval Medical Research Center

Locations

Naval Medical Research Center (NMRC) Clinical Trials Center

Bethesda, Maryland, United States

Countries

United States

References

Ophorst OJ, Radosevic K, Havenga MJ, Pau MG, Holterman L, Berkhout B, Goudsmit J, Tsuji M. Immunogenicity and protection of a recombinant human adenovirus serotype 35-based malaria vaccine against Plasmodium yoelii in mice. Infect Immun. 2006 Jan;74(1):313-20. doi: 10.1128/IAI.74.1.313-320.2006.

Reference Type: BACKGROUND

PMID: 16368986 (View on PubMed)

Li S, Locke E, Bruder J, Clarke D, Doolan DL, Havenga MJ, Hill AV, Liljestrom P, Monath TP, Naim HY, Ockenhouse C, Tang DC, Van Kampen KR, Viret JF, Zavala F, Dubovsky F. Viral vectors for malaria vaccine development. Vaccine. 2007 Mar 30;25(14):2567-74. doi: 10.1016/j.vaccine.2006.07.035. Epub 2006 Aug 1.

Reference Type: BACKGROUND

PMID: 16914237 (View on PubMed)

Rodrigues EG, Zavala F, Nussenzweig RS, Wilson JM, Tsuji M. Efficient induction of protective anti-malaria immunity by recombinant adenovirus. Vaccine. 1998 Nov;16(19):1812-7. doi: 10.1016/s0264-410x(98)00181-9.

Reference Type: BACKGROUND

PMID: 9795385 (View on PubMed)

Sedegah M, Peters B, Hollingdale MR, Ganeshan HD, Huang J, Farooq F, Belmonte MN, Belmonte AD, Limbach KJ, Diggs C, Soisson L, Chuang I, Villasante ED. Vaccine Strain-Specificity of Protective HLA-Restricted Class 1 P. falciparum Epitopes. PLoS One. 2016 Oct 3;11(10):e0163026. doi: 10.1371/journal.pone.0163026. eCollection 2016.

Reference Type: DERIVED

PMID: 27695088 (View on PubMed)

Aguiar JC, Bolton J, Wanga J, Sacci JB, Iriko H, Mazeika JK, Han ET, Limbach K, Patterson NB, Sedegah M, Cruz AM, Tsuboi T, Hoffman SL, Carucci D, Hollingdale MR, Villasante ED, Richie TL. Discovery of Novel Plasmodium falciparum Pre-Erythrocytic Antigens for Vaccine Development. PLoS One. 2015 Aug 20;10(8):e0136109. doi: 10.1371/journal.pone.0136109. eCollection 2015.

Reference Type: DERIVED

PMID: 26292257 (View on PubMed)

Sedegah M, Hollingdale MR, Farooq F, Ganeshan H, Belmonte M, Huang J, Abot E, Limbach K, Chuang I, Tamminga C, Epstein JE, Villasante E. Controlled Human Malaria Infection (CHMI) differentially affects cell-mediated and antibody responses to CSP and AMA1 induced by adenovirus vaccines with and without DNA-priming. Hum Vaccin Immunother. 2015;11(11):2705-15. doi: 10.1080/21645515.2015.1019186. Epub 2015 Aug 20.

Reference Type: DERIVED

PMID: 26292027 (View on PubMed)

Sedegah M, Hollingdale MR, Farooq F, Ganeshan H, Belmonte M, Kim Y, Peters B, Sette A, Huang J, McGrath S, Abot E, Limbach K, Shi M, Soisson L, Diggs C, Chuang I, Tamminga C, Epstein JE, Villasante E, Richie TL. Sterile immunity to malaria after DNA prime/adenovirus boost immunization is associated with effector memory CD8+T cells targeting AMA1 class I epitopes. PLoS One. 2014 Sep 11;9(9):e106241. doi: 10.1371/journal.pone.0106241. eCollection 2014.

Reference Type: DERIVED

PMID: 25211344 (View on PubMed)

Tamminga C, Sedegah M, Maiolatesi S, Fedders C, Reyes S, Reyes A, Vasquez C, Alcorta Y, Chuang I, Spring M, Kavanaugh M, Ganeshan H, Huang J, Belmonte M, Abot E, Belmonte A, Banania J, Farooq F, Murphy J, Komisar J, Richie NO, Bennett J, Limbach K, Patterson NB, Bruder JT, Shi M, Miller E, Dutta S, Diggs C, Soisson LA, Hollingdale MR, Epstein JE, Richie TL. Human adenovirus 5-vectored Plasmodium falciparum NMRC-M3V-Ad-PfCA vaccine encoding CSP and AMA1 is safe, well-tolerated and immunogenic but does not protect against controlled human malaria infection. Hum Vaccin Immunother. 2013 Oct;9(10):2165-77. doi: 10.4161/hv.24941. Epub 2013 Jun 4.

Reference Type: DERIVED

PMID: 23899517 (View on PubMed)

Tamminga C, Sedegah M, Regis D, Chuang I, Epstein JE, Spring M, Mendoza-Silveiras J, McGrath S, Maiolatesi S, Reyes S, Steinbeiss V, Fedders C, Smith K, House B, Ganeshan H, Lejano J, Abot E, Banania GJ, Sayo R, Farooq F, Belmonte M, Murphy J, Komisar J, Williams J, Shi M, Brambilla D, Manohar N, Richie NO, Wood C, Limbach K, Patterson NB, Bruder JT, Doolan DL, King CR, Diggs C, Soisson L, Carucci D, Levine G, Dutta S, Hollingdale MR, Ockenhouse CF, Richie TL. Adenovirus-5-vectored P. falciparum vaccine expressing CSP and AMA1. Part B: safety, immunogenicity and protective efficacy of the CSP component. PLoS One. 2011;6(10):e25868. doi: 10.1371/journal.pone.0025868. Epub 2011 Oct 7.

Reference Type: DERIVED

PMID: 22003411 (View on PubMed)

Sedegah M, Tamminga C, McGrath S, House B, Ganeshan H, Lejano J, Abot E, Banania GJ, Sayo R, Farooq F, Belmonte M, Manohar N, Richie NO, Wood C, Long CA, Regis D, Williams FT, Shi M, Chuang I, Spring M, Epstein JE, Mendoza-Silveiras J, Limbach K, Patterson NB, Bruder JT, Doolan DL, King CR, Soisson L, Diggs C, Carucci D, Dutta S, Hollingdale MR, Ockenhouse CF, Richie TL. Adenovirus 5-vectored P. falciparum vaccine expressing CSP and AMA1. Part A: safety and immunogenicity in seronegative adults. PLoS One. 2011;6(10):e24586. doi: 10.1371/journal.pone.0024586. Epub 2011 Oct 7.

Reference Type: DERIVED

PMID: 22003383 (View on PubMed)

Other Identifiers

HSRRB A-13453

Identifier Type: OTHER

Identifier Source: secondary_id

NMRC.2006.0001

Identifier Type: OTHER

Identifier Source: secondary_id

S-15-25

Identifier Type: -

Identifier Source: org_study_id