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

• Sponsor: U.S. Army Medical Research and Development Command (U.S. Fed)
• Overall Status: Completed
• CT.gov ID: NCT00392015
• Collaborator: United States Agency for International Development (USAID) (U.S. Fed), Congressionally Directed Medical Research Programs (U.S. Fed), Military Infectious Diseases Research Program (MIDRP) (Other), Naval Medical Research Center (U.S. Fed)
• Enrollment: 59
• Location: 1
• Arms: 2
• Actual Duration (Months): 131.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Plasmodium Falciparum	Biological: NMRC-M3V-Ad-PfCA; Biological: NMRC-MV-Ad-PfC, NMRC-M3V-Ad-PfCA	Phase 1/Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 59 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Two Part Clinical Trial Assessing the Safety, Tolerability, Immunogenicity and Protective Efficacy of NMRC-M3V-Ad-PfCA, a Multivalent, Adenovirus-Vectored Plasmodium Falciparum Malaria Vaccine, in Healthy, Malaria-Naïve Adults
• Actual Study Start Date: Oct 12, 2006
• Actual Primary Completion Date: Jun 2, 2016
• Actual Study Completion Date: Sep 25, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose-escalation NMRC-M3V-Ad-PfCA	Biological: NMRC-M3V-Ad-PfCA; Malaria Vaccine
Experimental: Regimen-comparison NMRC-MV-Ad-PfC, NMRC-M3V-Ad-PfCA	Biological: NMRC-MV-Ad-PfC, NMRC-M3V-Ad-PfCA; Malaria Vaccines

Outcome Measures

Primary Outcome Measures

1. Part A Dose-Escalation: Number of Participants Who Experienced Any Serious Adverse Events Related To Vaccine Administration [Through Study Completion, an average of 1 year]

   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.

2. Part B Regimen-Comparison: Number of Participants With Any Serious Adverse Events Related to Vaccine Administration [Through Study Completion, an average of 1 year]

   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.

3. Part B Regimen Comparison: Time to Parasitemia to Assess the Protective Efficacy Against Sporozoite Challenge (Pf, 3D7 Strain) [Through Study Completion, an average of 1 year]

   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.

Secondary Outcome Measures

1. 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]

   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].

2. 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]

   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].

3. 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]

   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. 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]

   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.

5. 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]

   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.

6. 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 [4 weeks post immunization]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Naval Medical Research Center (NMRC) Clinical Trials Center	Bethesda	Maryland	United States	20889-5607

Sponsors and Collaborators

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

Investigators

• Principal Investigator: Cindy Tamminga, MD, MPH, Naval Medical Research Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Military activity with primary responsibility for the conduct of this clinical trial.

Publications

• 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. Epub 2006 Aug 1. Review.
• Ophorst OJ, Radosević 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.
• 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.

• Responsible Party: U.S. Army Medical Research and Development Command
• ClinicalTrials.gov Identifier: NCT00392015
• Other Study ID Numbers: S-15-25; HSRRB A-13453; NMRC.2006.0001
• First Posted: Oct 25, 2006
• Last Update Posted: May 21, 2021
• Last Verified: Apr 1, 2021

• Keywords provided by U.S. Army Medical Research and Development Command: Malaria Vaccine; Adenovirus; Plasmodium falciparum
• Additional relevant MeSH terms: Malaria

Study Results

Participant Flow

Arm/Group Title	Group 1: NMRC-M3V-Ad-PfCA, 2x10^10 pu	Group 2: NMRC-M3V-Ad-PfCA, 1x10^11 pu	Group 3: NMRC-M3V-Ad-PfCA, 2x10^10 pu	Group 3: Infectivity Control	Group 4: NMRC-MV-Ad-PfC, 1x10^10 pu	Group 4: Infectivity Control
Arm/Group Description	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.	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.	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.	Infectivity control subjects were challenged with Group 3	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.	Infectivity control subjects were challenged with Group 4
Period Title: Overall Study
STARTED	6	6	20	6	15	6
COMPLETED	4	6	16	5	12	6
NOT COMPLETED	2	0	4	1	3	0

Baseline Characteristics

Arm/Group Title	Group 1: NMRC-M3V-Ad-PfCA, 2x10^10 pu	Group 2: NMRC-M3V-Ad-PfCA,1x10^11 pu	Group 3: NMRC-M3V-Ad-PfCA, 2x10^10 pu	Group 3: Infectivity Control	Group 4: NMRC-MV-Ad-PfC, 1x10^10 pu	Group 4: Infectivity Control	Total
Arm/Group Description	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.	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.	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.	Infectivity control subjects were challenged with Group 3 and Group 4	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.	Infectivity control subjects were challenged with Group 3 and Group 4	Total of all reporting groups
Overall Participants	6	6	20	6	15	6	59
Age, Customized (Count of Participants)
18-20 years	0 0%	1 16.7%	2 10%	0 0%	0 0%	0 0%	3 5.1%
21-30 years	3 50%	2 33.3%	10 50%	2 33.3%	4 26.7%	2 33.3%	23 39%
31-40 years	2 33.3%	1 16.7%	3 15%	3 50%	6 40%	1 16.7%	16 27.1%
41-50 years	1 16.7%	2 33.3%	5 25%	1 16.7%	5 33.3%	3 50%	17 28.8%
Sex: Female, Male (Count of Participants)
Female	1 16.7%	4 66.7%	6 30%	2 33.3%	4 26.7%	3 50%	20 33.9%
Male	5 83.3%	2 33.3%	14 70%	4 66.7%	11 73.3%	3 50%	39 66.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 16.7%	0 0%	3 15%	1 16.7%	1 6.7%	0 0%	6 10.2%
Not Hispanic or Latino	5 83.3%	6 100%	17 85%	5 83.3%	14 93.3%	6 100%	53 89.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	1 5%	0 0%	0 0%	0 0%	1 1.7%
Asian	0 0%	0 0%	0 0%	0 0%	2 13.3%	0 0%	2 3.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 33.3%	3 50%	9 45%	3 50%	8 53.3%	1 16.7%	26 44.1%
White	3 50%	3 50%	7 35%	2 33.3%	4 26.7%	5 83.3%	24 40.7%
More than one race	1 16.7%	0 0%	3 15%	1 16.7%	1 6.7%	0 0%	6 10.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%	6 100%	20 100%	6 100%	15 100%	6 100%	59 100%

Outcome Measures

1. Primary Outcome

Title	Part A Dose-Escalation: Number of Participants Who Experienced Any Serious Adverse Events Related To Vaccine Administration
Description	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.
Time Frame	Through Study Completion, an average of 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Group 1 received NMRC-M3V-Ad-PfCA (2 antigen combination) at a single low dose of 2x10^10 pu on Week 0	Group 2 received NMRC-M3V-Ad-PfCA (2 antigen combination) at a single high dose of 1x10^11 pu on Week 4.
Measure Participants	6	6
Count of Participants [Participants]	0 0%	0 0%

2. Primary Outcome

Title	Part B Regimen-Comparison: Number of Participants With Any Serious Adverse Events Related to Vaccine Administration
Description	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.
Time Frame	Through Study Completion, an average of 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 3	Group 4
Arm/Group Description	2 doses of NMRC-M3V-Ad-PfCA (2x10^10 pu) administered intramuscular 16 weeks apart on Week 16 and Week 32	2 doses of NMRC-MV-Ad-PfC (1x10^10 pu) administered intramuscular 16 weeks apart on Week 16 and Week 32
Measure Participants	20	15
Count of Participants [Participants]	0 0%	0 0%

3. Primary Outcome

Title	Part B Regimen Comparison: Time to Parasitemia to Assess the Protective Efficacy Against Sporozoite Challenge (Pf, 3D7 Strain)
Description	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.
Time Frame	Through Study Completion, an average of 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group 3	Group 3 Infectivity Control	Group 4	Group 4 Infectivity Control
Arm/Group Description	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 3 weeks later. Infectivity control subjects (not vaccinated) were also challenged.	Infectivity control subjects (not vaccinated) were also challenged	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 3 weeks later. Infectivity control subjects (not vaccinated) were also challenged.	Infectivity control subjects (not vaccinated) were also challenged
Measure Participants	20	6	15	6
Geometric Mean (Full Range) [days]	12.1	11.8	13.37	12.96

4. Secondary Outcome

Title	Part A Dose-Escalation: To Assess the Immunogenicity of NMRC-M3V-Ad-PfCA in Healthy Malaria-Naïve Adults Using ELISpot IFN-γ Responses
Description	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].
Time Frame	One month post immunization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Circumsporozoite Protein (CSP)	Apical Membrane Antigen-1 (AMA1)
Arm/Group Description	The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1)	The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1)
Measure Participants	6	6
Group 1	422	862
Group 2	154	423

5. Secondary Outcome

Title	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
Description	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].
Time Frame	22-23 days post immunization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Circumsporozoite Protein (CSP)	Apical Membrane Antigen-1 (AMA1)
Arm/Group Description	The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1)	The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1)
Measure Participants	20	20
Geometric Mean (Full Range) [sfc/m]	273	1303

6. Secondary Outcome

Title	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
Description	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].
Time Frame	4 weeks post immunization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Circumsporozoite Protein (CSP)
Arm/Group Description	Synthetic peptides derived from CSP
Measure Participants	15
Geometric Mean (Full Range) [sfc/m]	323

7. Secondary Outcome

Title	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
Description	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.
Time Frame	One month post immunization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Circumsporozoite Protein (CSP)	Apical Membrane Antigen-1 (AMA1)
Arm/Group Description	The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1)	The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1)
Measure Participants	6	6
Group 1 (% CD8+)	0.210	0.44
Group 1 (% CD4+)	0.044	0.086
Group 2 (% CD8+)	0.020	0.15
Group 2 (% CD4+)	0.006	0.035

8. Secondary Outcome

Title	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
Description	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.
Time Frame	22-23 days post immunization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Circumsporozoite Protein (CSP)	Apical Membrane Antigen-1 (AMA1)
Arm/Group Description	The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1)	The NMRC-M3V-Ad-PfCA vaccine combines two adenovectors encoding circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1)
Measure Participants	20	20
% CD4+ Cells	0.030	0.090
% CD8+ Cells	0.093	0.216

9. Secondary Outcome

Title	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
Description	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.
Time Frame	4 weeks post immunization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Circumsporozoite Protein (CSP)
Arm/Group Description	Synthetic peptides derived from CSP
Measure Participants	15
% CD4+ Cells	0.039
% CD8+ Cells	0.09

Adverse Events

Time Frame	Through Study Completion, an average of 1 year
Adverse Event Reporting Description	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.
Arm/Group Title	Group 1		Group 2		Group 3		Group 3 Infectivity Control		Group 4		Group 4 Infectivity Control
Arm/Group Description	Single low dose (2x10^10 pu) of NMRC-M3V-Ad-PfCA administered intramuscular on Week 0		Single high dose (1x10^11 pu) of NMRC-M3V-Ad-PfCA administered intramuscular on Week 4		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.		Infectivity Control (not vaccinated) were also challenged		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.		Infectivity Control (not vaccinated) were also challenged
All Cause Mortality
	Group 1		Group 2		Group 3		Group 3 Infectivity Control		Group 4		Group 4 Infectivity Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)		0/20 (0%)		1/6 (16.7%)		0/15 (0%)		0/6 (0%)
Serious Adverse Events
	Group 1		Group 2		Group 3		Group 3 Infectivity Control		Group 4		Group 4 Infectivity Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		0/6 (0%)		0/20 (0%)		1/6 (16.7%)		0/15 (0%)		0/6 (0%)
Psychiatric disorders
Depression	1/6 (16.7%)		0/6 (0%)		0/20 (0%)		0/6 (0%)		0/15 (0%)		0/6 (0%)
Suicide	0/6 (0%)		0/6 (0%)		0/20 (0%)		1/6 (16.7%)		0/15 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	Group 1		Group 2		Group 3		Group 3 Infectivity Control		Group 4		Group 4 Infectivity Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/6 (83.3%)		5/6 (83.3%)		9/20 (45%)		0/0 (NaN)		13/15 (86.7%)		0/0 (NaN)
Eye disorders
Blurred vision	0/6 (0%)		1/6 (16.7%)		0/20 (0%)		0/0 (NaN)		0/15 (0%)		0/0 (NaN)
Pink eye/conjunctivitis D	0/6 (0%)		0/6 (0%)		0/20 (0%)		0/0 (NaN)		1/15 (6.7%)		1/0 (Infinity)
Eye pain/irritation	0/6 (0%)		0/6 (0%)		0/20 (0%)		0/0 (NaN)		1/15 (6.7%)		1/0 (Infinity)
Gastrointestinal disorders
Nausea/vomiting	2/6 (33.3%)		3/6 (50%)		2/20 (10%)		2/0 (Infinity)		2/15 (13.3%)		2/0 (Infinity)
Diarrhea	0/6 (0%)		1/6 (16.7%)		0/20 (0%)		0/0 (NaN)		2/15 (13.3%)		2/0 (Infinity)
General disorders
Pain/tenderness	5/6 (83.3%)		5/6 (83.3%)		9/20 (45%)		9/0 (Infinity)		13/15 (86.7%)		13/0 (Infinity)
Erythema	0/6 (0%)		0/6 (0%)		1/20 (5%)		1/0 (Infinity)		0/15 (0%)		0/0 (NaN)
Induration/swelling	0/6 (0%)		1/6 (16.7%)		1/20 (5%)		1/0 (Infinity)		0/15 (0%)		0/0 (NaN)
Warmth	0/6 (0%)		1/6 (16.7%)		2/20 (10%)		2/0 (Infinity)		0/15 (0%)		0/0 (NaN)
Hives	0/6 (0%)		0/6 (0%)		1/20 (5%)		1/0 (Infinity)		0/15 (0%)		0/0 (NaN)
Lymphadenopathy	2/6 (33.3%)		0/6 (0%)		0/20 (0%)		0/0 (NaN)		0/15 (0%)		0/0 (NaN)
Limited arm motion	1/6 (16.7%)		0/6 (0%)		0/20 (0%)		0/0 (NaN)		0/15 (0%)		0/0 (NaN)
Malaise	1/6 (16.7%)		4/6 (66.7%)		3/20 (15%)		3/0 (Infinity)		2/15 (13.3%)		2/0 (Infinity)
Fever	1/6 (16.7%)		4/6 (66.7%)		2/20 (10%)		2/0 (Infinity)		1/15 (6.7%)		1/0 (Infinity)
Chills	0/6 (0%)		4/6 (66.7%)		2/20 (10%)		2/0 (Infinity)		1/15 (6.7%)		1/0 (Infinity)
Fatigue	0/6 (0%)		0/6 (0%)		5/20 (25%)		5/0 (Infinity)		2/15 (13.3%)		2/0 (Infinity)
Musculoskeletal and connective tissue disorders
Myalgia	2/6 (33.3%)		2/6 (33.3%)		3/20 (15%)		3/0 (Infinity)		2/15 (13.3%)		2/0 (Infinity)
Arthralgia	1/6 (16.7%)		1/6 (16.7%)		1/20 (5%)		1/0 (Infinity)		0/15 (0%)		0/0 (NaN)
Nervous system disorders
Headache	2/6 (33.3%)		3/6 (50%)		3/20 (15%)		3/0 (Infinity)		2/15 (13.3%)		2/0 (Infinity)
Dizziness	0/6 (0%)		1/6 (16.7%)		1/20 (5%)		1/0 (Infinity)		1/15 (6.7%)		1/0 (Infinity)
Respiratory, thoracic and mediastinal disorders
Cough	0/6 (0%)		0/6 (0%)		1/20 (5%)		1/0 (Infinity)		0/15 (0%)		0/0 (NaN)
Pharyngitis	0/6 (0%)		0/6 (0%)		1/20 (5%)		1/0 (Infinity)		1/15 (6.7%)		1/0 (Infinity)
Nasal congestion	0/6 (0%)		0/6 (0%)		0/20 (0%)		0/0 (NaN)		1/15 (6.7%)		1/0 (Infinity)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.