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

NCT00392015 | Completed Phase 1 Results

• 3 other identifiers: S-15-25HSRRB A-13453NMRC.2006.0001
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

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.

Conditions

Plasmodium Falciparum

Keywords

Malaria Vaccine; Adenovirus; Plasmodium falciparum

Outcome Measures

Primary Outcomes (3)

• Part A Dose-Escalation: Number of Participants Who Experienced Any Serious Adverse Events Related To Vaccine Administration

  To assess the safety and tolerability of NMRC-M3V-Ad-PfCA, in a dose-escalation design (Part A), in healthy malaria-naïve adults. Part A was a dose escalation of NMRC-M3V-AdPfCA (2 antigen combination) using two dose groups, 2x10\^10 pu (Group 1) and 1x10\^11 pu (Group 2). Subjects received a single intramuscular injection with the injections in the 2 groups staggered by 4 weeks in order to assess the safety and tolerability of the vaccine and define the dose to be used in Part B. The vaccine was to be considered safe and well-tolerated if there were no severe or serious adverse events related to vaccine administration.

  Through Study Completion, an average of 1 year

• Part B Regimen-Comparison: Number of Participants With Any Serious Adverse Events Related to Vaccine Administration

  To assess the safety and tolerability of NMRC-M3V-Ad-PfCA, in a regimen-comparison design (Part B), in healthy malaria-naïve adults. Subjects in part B received 2 intramuscular injections given 16 weeks apart: Group 3 NMRC-M3V-Ad-PfCA (2 antigen combination) at a dose of 2x10\^10 pu, or Group 4 NMRC-MV-Ad-PfC (single antigen) at 1x10\^10 pu dose. The vaccine was to be considered safe and well-tolerated if there were no severe or serious adverse events related to vaccine administration.

  Through Study Completion, an average of 1 year

• Part B Regimen Comparison: Time to Parasitemia to Assess the Protective Efficacy Against Sporozoite Challenge (Pf, 3D7 Strain)

  Protective efficacy was assessed by conducting a homologous 3D7 strain sporozoite challenge 3 weeks after the second NMRCMV-Ad-PfC immunization. Time to parasitemia was measured in both vaccinated and unvaccinated volunteers (infectivity controls) in Group 3 (NMRC-M3V-Ad-PfCA (2 antigen combination) at a dose of 2x10\^10 pu) and Group 4 (NMRC-MV-Ad-PfC (single antigen) at 1x10\^10 pu dose). Infectivity control subjects were challenged with Group 3 and Group 4. Each volunteer was monitored for the onset of signs and symptoms of malaria and by daily Giemsa-stained thick blood films with positive films confirmed by a second reader. The identity of immunized and non-immunized volunteers was known to the clinical trial staff but not to the microscopists reading the malaria smears.

  Through Study Completion, an average of 1 year

Secondary Outcomes (6)

• Part A Dose-Escalation: To Assess the Immunogenicity of NMRC-M3V-Ad-PfCA in Healthy Malaria-Naïve Adults Using ELISpot IFN-γ Responses

  One month post immunization

• Part B Regimen-Comparison: To Assess the Immunogenicity of NMRC-M3V-Ad-PfCA in Healthy Malaria-Naïve Adults Using ELISpot IFN-γ Responses in Group 3

  22-23 days post immunization

• Part B Regimen-Comparison: To Assess the Immunogenicity of NMRC-MV-Ad-PfC in Healthy Malaria-Naïve Adults Using ELISpot IFN-γ Responses in Group 4

  4 weeks post immunization

• Part A Dose-Escalation: To Assess the Immunogenicity of NMRC-M3V-Ad-PfCA in Healthy Malaria-Naïve Adults Using Intracellular Cytokine Staining of CD4+ and CD8+ T Cell IFN-γ Responses

  One month post immunization

• Part B Regimen-Comparison: To Assess the Immunogenicity of NMRC-M3V-Ad-PfCA in Healthy Malaria-Naïve Adults Using Intracellular Cytokine Staining CD4+ and CD8+ T Cell IFN-γ Responses in Group 3

  22-23 days post immunization

Study Arms (2)

Dose-escalation

EXPERIMENTAL

NMRC-M3V-Ad-PfCA

Biological: NMRC-M3V-Ad-PfCA

Regimen-comparison

EXPERIMENTAL

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

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

Interventions

NMRC-M3V-Ad-PfCA BIOLOGICAL

Malaria Vaccine

Dose-escalation

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

Malaria Vaccines

Regimen-comparison

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• United States Agency for International Development (USAID): collaborator
• Congressionally Directed Medical Research Programs: collaborator
• Military Infectious Diseases Research Program (MIDRP): collaborator
• Naval Medical Research Center: collaborator

Study Sites (1)

Naval Medical Research Center (NMRC) Clinical Trials Center

Bethesda, Maryland, 20889-5607, United States

Location

Related Publications (10)

• 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.

  PMID: 16368986 BACKGROUND

• 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.

  PMID: 16914237 BACKGROUND

• 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.

  PMID: 9795385 BACKGROUND

• 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.

  PMID: 27695088 DERIVED

• 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.

  PMID: 26292257 DERIVED

• 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.

  PMID: 26292027 DERIVED

• 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.

  PMID: 25211344 DERIVED

• 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.

  PMID: 23899517 DERIVED

• 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.

  PMID: 22003411 DERIVED

• 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.

  PMID: 22003383 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Adenoviridae Infections

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; DNA Virus Infections; Virus Diseases

Results Point of Contact

• Title: Dr. Judith Epstein
• Organization: United States Military Malaria Vaccine Program Naval Medical Research Center

judith.epstein@med.navy.mil

301-252-9026

Study Officials

• Cindy Tamminga, MD, MPH

  Naval Medical Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2006
• First Posted: October 25, 2006
• Study Start: October 12, 2006
• Primary Completion: June 2, 2016
• Study Completion: September 25, 2017
• Last Updated: May 21, 2021
• Results First Posted: May 21, 2021

Record last verified: 2021-04

Locations

US (1)