Clinical Trial for Malaria Vaccines to Test for Safety, Immune Response and Protection Against Malaria

NCT00870987 | Completed Phase 1

• 3 other identifiers: WRAIR 1550HRPO #A-15350NMRC.2009.0004
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test the safety and effectiveness of a new malaria vaccine, the DNA-Ad vaccine. The study is specifically looking at a vaccine regimen against Plasmodium falciparum, the most deadly form of malaria.

Conditions

Malaria

Keywords

Malaria; Vaccine

Outcome Measures

Primary Outcomes (1)

• Number of adverse events

  The vaccine will be considered safe and well-tolerated if there are no severe or serious adverse events (AE) related to vaccine administration or if any severe events are relatively benign (e.g. erythema meeting criteria for severe due to its dimensions but not significantly affecting the activities of daily living for the subject) or brief in duration (e.g. less than 48 hours). The AEs will be assessed according to the method below. 1. Occurrence, severity, and duration of any solicited symptoms starting on the day of immunization through day 7 after each immunization 2. Occurrence of any unsolicited symptoms, abnormal physical findings, and laboratory values starting from the day of immunization through day 28 after each immunization 3. Occurrence of any serious adverse events, as defined in 21 CFR 312.32, during the five-year study period

  5 years

Secondary Outcomes (3)

• Number of sterile or partial protections

  28 days after malaria challenge

• Number of humoral immunity expressions

  28 days after malaria challenge

• Number of cellular immunity expressions

  28 days after malaria challenge

Study Arms (2)

1

EXPERIMENTAL

DNA vaccine prime Given at 0, 4, and 8 weeks

Biological: DNA vaccine prime

2

EXPERIMENTAL

adenovirus type 5 vaccine boost Given at 24 weeks

Biological: adenovirus type 5 vaccine boost

Interventions

DNA vaccine prime BIOLOGICAL

2 mg total dose (1 mg per construct in a volume of 1 mL)

1

adenovirus type 5 vaccine boost BIOLOGICAL

2 x 1010 particle units (pu) (1 x 1010 pu per each of 2 constructs including CSP and AMA1 respectively)

2

Eligibility Criteria

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

You may qualify if:

• Healthy adults 18 to 50 years of age (inclusive)
• Women who are not pregnant by a current negative pregnancy test or of non-childbearing potential
• Willing to use an FDA approved birth control method including condoms, birth control pills, sterility surgery, or intrauterine devices among others, from time of enrollment until 6 months after the end of the active phase of the study
• Able to provide free and willing written informed consent to participate
• Score at least 80% correct on a 10 question Assessment of Understanding
• No plans to travel to a malaria endemic area during the course of the study
• Free of significant health problems as established by medical history and clinical examination completed prior to the study
• Available to participate and reachable for duration of study (up to five years)
• Only subjects with no or low cardiac risk factors according to the Gaziano study \[53\] and a normal EKG will be included in the study

You may not qualify if:

• Pregnant (positive HCG) or nursing at screening or plans to become pregnant or nurse from the time of enrollment until 6 months after sporozoite challenge
• Any past history of malaria
• History of receipt of malaria vaccine
• Plans to travel to malarious areas during the study period
• Use of any investigational or non-registered drug or vaccine within 30 days prior to enrollment
• Seropositive for HIV, hepatitis C virus (antibodies to HIV and HCV), and/or HBsAg
• Subjects in the immunized group who engage in high-risk behaviors for acquiring HIV
• History of psoriasis (given its interaction with chloroquine)
• Use or planned use of any drugs with significant anti-malarial activity, such as doxycycline, clindamycin, azithromycin, or trimethoprim/sulfamethoxazole among others during the study period (subjects can withhold the use of these medications during the study period if approved by their primary care physicians, at the minimum starting from four weeks before vaccine administration until four weeks after becoming parasitemic) Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection and history of splenectomy
• Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of challenge
• A family history of congenital or hereditary immunodeficiency
• Chronic or active neurologic disease including seizure disorder
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by medical history, physical examination, or abnormal baseline laboratory screening tests.
• Abnormal baseline EKG obtained at screening
• Acute disease at the time of enrollment

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• United States Agency for International Development (USAID): collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator

Study Sites (1)

Clinical Trials Center, WRAIR

Silver Spring, Maryland, 20910, United States

Location

Related Publications (6)

• 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

• Chuang I, Sedegah M, Cicatelli S, Spring M, Polhemus M, Tamminga C, Patterson N, Guerrero M, Bennett JW, McGrath S, Ganeshan H, Belmonte M, Farooq F, Abot E, Banania JG, Huang J, Newcomer R, Rein L, Litilit D, Richie NO, Wood C, Murphy J, Sauerwein R, Hermsen CC, McCoy AJ, Kamau E, Cummings J, Komisar J, Sutamihardja A, Shi M, Epstein JE, Maiolatesi S, Tosh D, Limbach K, Angov E, Bergmann-Leitner E, Bruder JT, Doolan DL, King CR, Carucci D, Dutta S, Soisson L, Diggs C, Hollingdale MR, Ockenhouse CF, Richie TL. DNA prime/Adenovirus boost malaria vaccine encoding P. falciparum CSP and AMA1 induces sterile protection associated with cell-mediated immunity. PLoS One. 2013;8(2):e55571. doi: 10.1371/journal.pone.0055571. Epub 2013 Feb 14.

  PMID: 23457473 DERIVED

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• Judith Epstein, MD

  US Military Vaccine Program, NMRC PI, Naval Officer

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 27, 2009
• First Posted: March 30, 2009
• Study Start: May 1, 2009
• Primary Completion: April 1, 2014
• Study Completion: July 1, 2015
• Last Updated: February 11, 2021

Record last verified: 2021-02

Locations

US (1)