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| ID | Type | Description | Link |
|---|---|---|---|
| HSRRB A-13453 | Other Identifier | WRAIR | |
| NMRC.2006.0001 | Other Identifier | NMRC |
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| Name | Class |
|---|---|
| United States Agency for International Development (USAID) | FED |
| Congressionally Directed Medical Research Programs | FED |
| Military Infectious Diseases Research Program (MIDRP) | NETWORK |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose-escalation | Experimental | NMRC-M3V-Ad-PfCA |
|
| Regimen-comparison | Experimental | NMRC-MV-Ad-PfC, NMRC-M3V-Ad-PfCA |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| NMRC-M3V-Ad-PfCA | Biological | Malaria Vaccine |
| |
| NMRC-MV-Ad-PfC, NMRC-M3V-Ad-PfCA |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Part A Dose-Escalation: To Assess the Immunogenicity of NMRC-M3V-Ad-PfCA in Healthy Malaria-Naïve Adults Using ELISpot IFN-γ Responses | The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). In Group 1 healthy volunteers received one intramuscular injection of 2x10^10 pu at Week 0 and in Group 2 a five-fold higher dose of 1 x 10^11 pu at Week 4. Immunogenicity was assessed by ELISpot IFN-γ responses against synthetic peptides derived from CSP and AMA1 as the range of spot forming cells/million peripheral blood mononuclear cells [sfc/m]. |
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INCLUSION CRITERIA:
EXCLUSION CRITERIA:
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| Name | Affiliation | Role |
|---|---|---|
| Cindy Tamminga, MD, MPH | Naval Medical Research Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Naval Medical Research Center (NMRC) Clinical Trials Center | Bethesda | Maryland | 20889-5607 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16368986 | Background | 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. | |
| 16914237 | Background |
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| ID | Title | Description |
|---|---|---|
| FG000 | Group 1: NMRC-M3V-Ad-PfCA, 2x10^10 pu | Part A is a dose escalation of NMRC-M3V-Ad-PfCA (2 antigen combination) using 2 dose groups: Group 1 received a single low dose of 2x10^10 pu and Group 2 received a single high dose of 1x10^11 pu. Injections were 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. |
| FG001 | Group 2: NMRC-M3V-Ad-PfCA, 1x10^11 pu | Part A is a dose escalation of NMRC-M3V-Ad-PfCA (2 antigen combination) using 2 dose groups: Group 1 received a single low dose of 2x10^10 pu and Group 2 received a single high dose of 1x10^11 pu. Injections were 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. |
| FG002 | Group 3: NMRC-M3V-Ad-PfCA, 2x10^10 pu | Part B is the challenge phase to assess protective efficacy. 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. Infectivity control subjects were challenged with Group 3 and Group 4. |
| FG003 | Group 3: Infectivity Control | Infectivity control subjects were challenged with Group 3 |
| FG004 | Group 4: NMRC-MV-Ad-PfC, 1x10^10 pu | Part B is the challenge phase to assess protective efficacy. 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. Infectivity control subjects were challenged with Group 3 and Group 4. |
| FG005 | Group 4: Infectivity Control | Infectivity control subjects were challenged with Group 4 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Group 1: NMRC-M3V-Ad-PfCA, 2x10^10 pu | Part A is a dose escalation of NMRC-M3V-Ad-PfCA (2 antigen combination) using 2 dose groups: Group 1 received a single low dose of 2x10^10 pu and Group 2 received a single high dose of 1x10^11 pu. Injections were 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Count of Participants | Participants | Through Study Completion, an average of 1 year |
|
Through Study Completion, an average of 1 year
Occurrence of solicited adverse events over a 14-day follow-up period (day of vaccination and 13 subsequent days) and unsolicited adverse events over a 30 day follow-up period (day of immunization and 29 subsequent days) in vaccinated subjects Groups 1-4. Other (Not Including Serious) Adverse Events were not collected for the infected control group. Serious adverse events during the one year active study period in vaccinated subjects Groups 1-4 and non-vaccinated infectivity control subjects.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group 1 | Single low dose (2x10^10 pu) of NMRC-M3V-Ad-PfCA administered intramuscular on Week 0 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Depression | Psychiatric disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pain/tenderness | General disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Judith Epstein | United States Military Malaria Vaccine Program Naval Medical Research Center | 301-252-9026 | judith.epstein@med.navy.mil |
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| ID | Term |
|---|---|
| D016778 | Malaria, Falciparum |
| D000257 | Adenoviridae Infections |
| ID | Term |
|---|---|
| D008288 | Malaria |
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
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| Naval Medical Research Center | FED |
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| Biological |
Malaria Vaccines |
|
| Through Study Completion, an average of 1 year |
| 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 | The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). Group 3 healthy volunteers received 2 intramuscular injections of NMRC-M3V-Ad-PfCA (2 antigen combination) at a dose of 2x10^10 pu at Week 16 and Week 32. Immunogenicity was assessed by ELISpot IFN-γ responses against synthetic peptides derived from CSP and AMA1 using peripheral blood mononuclear cells during the study. IFN-γ ELISpot responses were measured as the range of spot forming cells/million peripheral blood mononuclear cells [sfc/m]. | 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 | Group 4 healthy volunteers received 2 intramuscular injections of NMRC-MV-Ad-PfC (single antigen) at a dose of 1x10^10 pu at Week 16 and Week 32. Immunogenicity was assessed by ELISpot IFN-γ responses against synthetic peptides derived from circumsporozoite protein (CSP) using peripheral blood mononuclear cells during the study. IFN-γ ELISpot responses measured as the range of spot forming cells/million peripheral blood mononuclear cells [sfc/m]. | 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 | The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). In Group 1 healthy volunteers received one intramuscular injection of 2x10^10 pu at Week 0 and in Group 2 a five-fold higher dose of 1 x 10^11 pu at Week 4. Immunogenicity was assessed by Intracellular Cytokine Staining of CD4+ and CD8+ T cell IFN-γ responses to AMA1 and CSP using peripheral blood mononuclear cells during the study. CD4+ and CD8+ T cell IFN-γ responses were measured as percentage (%) range of positive 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 | The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). Group 3 healthy volunteers received 2 intramuscular injections of NMRC-M3V-Ad-PfCA (2 antigen combination) at a dose of 2x10^10 pu at Week 16 and Week 32. Immunogenicity was assessed by Intracellular Cytokine Staining of CD4+ and CD8+ T cell IFN-γ responses to AMA1 and CSP measured using peripheral blood mononuclear cells during the study. CD4+ and CD8+ T cell IFN-γ responses were measured as percentage (%) range of positive responses. | 22-23 days post immunization |
| Part B Regimen-Comparison: To Assess the Immunogenicity of NMRC-MV-Ad-PfC in Healthy Malaria-Naïve Adults Using Intracellular Cytokine Staining of CD4+ and CD8+ T Cell IFN-γ Responses in Group 4 | Group 4 healthy volunteers received 2 intramuscular injections of NMRC-MV-Ad-PfC (single antigen) at a dose of 1x10^10 pu at Week 16 and Week 32. Immunogenicity was assessed by Intracellular Cytokine Staining of CD4+ and CD8+ T cell IFN-γ responses to synthetic peptides derived from circumsporozoite protein (CSP) using peripheral blood mononuclear cells during the study. CD4+ and CD8+ T cell IFN-γ responses were measured as percentage (%) range of positive responses. | 4 weeks post immunization |
| 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. |
| 9795385 | 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. |
| 27695088 | Derived | 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. |
| 26292257 | 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. |
| 26292027 | 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. |
| 25211344 | 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. |
| 23899517 | 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. |
| 22003411 | 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. |
| 22003383 | 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. |
| Withdrawal by Subject |
|
| Adverse Event |
|
| Previous trial recipient |
|
| BG001 | Group 2: NMRC-M3V-Ad-PfCA,1x10^11 pu | Part A is a dose escalation of NMRC-M3V-Ad-PfCA (2 antigen combination) using 2 dose groups: Group 1 received a single low dose of 2x10^10 pu and Group 2 received a single high dose of 1x10^11 pu. Injections were 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. |
| BG002 | Group 3: NMRC-M3V-Ad-PfCA, 2x10^10 pu | Part B is the challenge phase to assess protective efficacy. 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. Infectivity control subjects were challenged with Group 3 and Group 4. |
| BG003 | Group 3: Infectivity Control | Infectivity control subjects were challenged with Group 3 and Group 4 |
| BG004 | Group 4: NMRC-MV-Ad-PfC, 1x10^10 pu | Part B is the challenge phase to assess protective efficacy. 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. Infectivity control subjects were challenged with Group 3 and Group 4. |
| BG005 | Group 4: Infectivity Control | Infectivity control subjects were challenged with Group 3 and Group 4 |
| BG006 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Asian/Pacific Islander fall under one category in the study and the number of participants in this category are noted under Asian in the baseline measure table | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Group 2 | Group 2 received NMRC-M3V-Ad-PfCA (2 antigen combination) at a single high dose of 1x10^11 pu on Week 4. |
|
|
| Primary | 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. | Posted | Count of Participants | Participants | Through Study Completion, an average of 1 year |
|
|
|
| Primary | 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. | Posted | Geometric Mean | Full Range | days | Through Study Completion, an average of 1 year |
|
|
|
| Secondary | Part A Dose-Escalation: To Assess the Immunogenicity of NMRC-M3V-Ad-PfCA in Healthy Malaria-Naïve Adults Using ELISpot IFN-γ Responses | The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). In Group 1 healthy volunteers received one intramuscular injection of 2x10^10 pu at Week 0 and in Group 2 a five-fold higher dose of 1 x 10^11 pu at Week 4. Immunogenicity was assessed by ELISpot IFN-γ responses against synthetic peptides derived from CSP and AMA1 as the range of spot forming cells/million peripheral blood mononuclear cells [sfc/m]. | Posted | Geometric Mean | Full Range | sfc/m | One month post immunization |
|
|
|
| Secondary | 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 | The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). Group 3 healthy volunteers received 2 intramuscular injections of NMRC-M3V-Ad-PfCA (2 antigen combination) at a dose of 2x10^10 pu at Week 16 and Week 32. Immunogenicity was assessed by ELISpot IFN-γ responses against synthetic peptides derived from CSP and AMA1 using peripheral blood mononuclear cells during the study. IFN-γ ELISpot responses were measured as the range of spot forming cells/million peripheral blood mononuclear cells [sfc/m]. | Posted | Geometric Mean | Full Range | sfc/m | 22-23 days post immunization |
|
|
|
| Secondary | 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 | Group 4 healthy volunteers received 2 intramuscular injections of NMRC-MV-Ad-PfC (single antigen) at a dose of 1x10^10 pu at Week 16 and Week 32. Immunogenicity was assessed by ELISpot IFN-γ responses against synthetic peptides derived from circumsporozoite protein (CSP) using peripheral blood mononuclear cells during the study. IFN-γ ELISpot responses measured as the range of spot forming cells/million peripheral blood mononuclear cells [sfc/m]. | Posted | Geometric Mean | Full Range | sfc/m | 4 weeks post immunization |
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| Secondary | 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 | The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). In Group 1 healthy volunteers received one intramuscular injection of 2x10^10 pu at Week 0 and in Group 2 a five-fold higher dose of 1 x 10^11 pu at Week 4. Immunogenicity was assessed by Intracellular Cytokine Staining of CD4+ and CD8+ T cell IFN-γ responses to AMA1 and CSP using peripheral blood mononuclear cells during the study. CD4+ and CD8+ T cell IFN-γ responses were measured as percentage (%) range of positive responses. | Posted | Geometric Mean | Full Range | percentage of cells | One month post immunization |
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| Secondary | 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 | The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). Group 3 healthy volunteers received 2 intramuscular injections of NMRC-M3V-Ad-PfCA (2 antigen combination) at a dose of 2x10^10 pu at Week 16 and Week 32. Immunogenicity was assessed by Intracellular Cytokine Staining of CD4+ and CD8+ T cell IFN-γ responses to AMA1 and CSP measured using peripheral blood mononuclear cells during the study. CD4+ and CD8+ T cell IFN-γ responses were measured as percentage (%) range of positive responses. | Posted | Geometric Mean | Full Range | percentage of cells | 22-23 days post immunization |
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| Secondary | Part B Regimen-Comparison: To Assess the Immunogenicity of NMRC-MV-Ad-PfC in Healthy Malaria-Naïve Adults Using Intracellular Cytokine Staining of CD4+ and CD8+ T Cell IFN-γ Responses in Group 4 | Group 4 healthy volunteers received 2 intramuscular injections of NMRC-MV-Ad-PfC (single antigen) at a dose of 1x10^10 pu at Week 16 and Week 32. Immunogenicity was assessed by Intracellular Cytokine Staining of CD4+ and CD8+ T cell IFN-γ responses to synthetic peptides derived from circumsporozoite protein (CSP) using peripheral blood mononuclear cells during the study. CD4+ and CD8+ T cell IFN-γ responses were measured as percentage (%) range of positive responses. | Posted | Geometric Mean | Full Range | percentage of cells | 4 weeks post immunization |
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| 0 |
| 6 |
| 1 |
| 6 |
| 5 |
| 6 |
| EG001 | Group 2 | Single high dose (1x10^11 pu) of NMRC-M3V-Ad-PfCA administered intramuscular on Week 4 | 0 | 6 | 0 | 6 | 5 | 6 |
| EG002 | Group 3 | 2 doses of NMRC-M3V-Ad-PfCA (2x10^10 pu) administered intramuscular 16 weeks apart on Week 16 and Week 32 followed by a sporozoite challenge 2 to 4 weeks after the second immunization. | 0 | 20 | 0 | 20 | 9 | 20 |
| EG003 | Group 3 Infectivity Control | Infectivity Control (not vaccinated) were also challenged | 1 | 6 | 1 | 6 | 0 | 0 |
| EG004 | Group 4 | 2 doses of NMRC-MV-Ad-PfC (1x10^10 pu) administered intramuscular 16 weeks apart on Week 16 and Week 32 followed by a sporozoite challenge 2 to 4 weeks after the second immunization. | 0 | 15 | 0 | 15 | 13 | 15 |
| EG005 | Group 4 Infectivity Control | Infectivity Control (not vaccinated) were also challenged | 0 | 6 | 0 | 6 | 0 | 0 |
| Suicide | Psychiatric disorders | Systematic Assessment |
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| Erythema | General disorders | Systematic Assessment |
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| Induration/swelling | General disorders | Systematic Assessment |
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| Warmth | General disorders | Systematic Assessment |
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| Hives | General disorders | Systematic Assessment |
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| Lymphadenopathy | General disorders | Systematic Assessment |
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| Limited arm motion | General disorders | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Malaise | General disorders | Systematic Assessment |
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| Fever | General disorders | Systematic Assessment |
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| Chills | General disorders | Systematic Assessment |
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| Myalgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Nausea/vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Blurred vision | Eye disorders | Systematic Assessment |
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| Dizziness | Nervous system disorders | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Pharyngitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Pink eye/conjunctivitis D | Eye disorders | Systematic Assessment |
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| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Eye pain/irritation | Eye disorders | Systematic Assessment |
|
Not provided
Not provided
| D000096724 |
| Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| Group 2 (% CD8+) |
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| Group 2 (% CD4+) |
|