Trial to Evaluate the Safety, Immunogenicity, and Efficacy of Malaria Infection in Malaria Naïve Adults

NCT03341754 | Completed Phase 1 FDA Drug

• 3 other identifiers: S-14-07NMRC.2016.0006NavOx
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 2

Brief Summary

This is a study designed to assess the safety, tolerability, immunogenicity, and protective efficacy of 2 heterologous prime-boost vaccine regimens in healthy, malaria naïve adults. The study will include 2 vaccine groups and an infectivity control (IC) group consisting of non-immunized subjects. Subjects to be immunized will be randomly assigned to one of two vaccine groups.

Conditions

Malaria

Keywords

Malaria Infection

Outcome Measures

Primary Outcomes (4)

• Occurrence of Serious Adverse Events

  Occurrence of Serious Adverse Events following immunization through day 7 after each immunization

  Through day 7 after each immunization

• Occurrence of Abnormal Physical Symptoms (Clinical Abnormalities)

  Occurrence of Abnormal Physical Findings following immunization through day 28 after each immunization. Grading Scale: Grade 1= No interference with activity; Grade 2= Some interference with activity; Grade 3=Prevents daily activity; Grade 4= ER visit or hospitalization

  Through day 28 after each immunization

• Occurrence of Abnormal Laboratory Values

  Occurrence of Abnormal Laboratory Values following immunization through day 28 after each immunization

  Through day 28 after each immunization

• Occurrence of Any Serious Adverse Events Throughout the Study Period

  Occurrence of Any Serious Adverse Events Throughout the Study Period, from enrollment through 3 months after CHMI

  Enrollment through 3 months after CHMI

Secondary Outcomes (4)

• Vaccine Efficacy Determined by Time to Development of Parasitemia

  after CHMI: Days 7 - 28

• Measurement of Antibody Titers Against Sporozoite and Erythrocyte Stage Parasites

  Days 231 and 286

• Measure of correlation between pre-immunization HuAd5 neutralizing antibody titers and the protective efficacy against CHMI and humoral and cellular immune responses of the 2 prime-boost regimens

  HuAd5: Days -14 to -1; Cellular Immunity: Days -14 to -1, 84, 168 and 195; Humoral Immunity: Days -14 to -1, 14, 28, 42, 56, 70, 84, 168, 195

• Comparison of Immunogenicity of the 2 Vaccine Regimens

  Days 1 - 286

Study Arms (3)

Group 1 (D/ChAd63-CA)

EXPERIMENTAL

(2-antigen): 3 doses at 4 week intervals (Week 0, 4, and 8) of DNA prime with D-C + D-A at 2 mg total (1 mg per construct) per dose as two 1 mL IM injections of the blended D-CA, one in each arm, via Biojector 2000 needle-free injection device or an equivalent disposable syringe needle-free injection device. This will be followed after 16 weeks (Week 24) by 1 dose of ChAd63-C + ChAd63-A boost, at a total dose of 1 x 1011 virus particles (vp) (5 x 1010 vp/construct) as a single IM injection of 0.65mL, using a needle and syringe. Week 0 = Prime with D-CA Week 4 = Prime with D-CA Week 8 = Prime with D-CA Week 24 = Boost with ChAd63-CA Week 28 = Controlled Human Malaria Infection (CHMI)

Biological: D/ChAd63-CA

Group 2 (D/ChAd63-CAT)

EXPERIMENTAL

(3-antigen): 3 doses at 4 week intervals (Week 0, 4, and 8) of DNA prime with D-C + D-A + D-T at 3 mg total (1 mg per construct) per dose as two 1 mL intramuscular (IM) injections of the blended D-CAT, one in each arm, via Biojector 2000 needle-free injection device or an equivalent disposable syringe needle-free injection device. This will be followed after 16 weeks (Week 24) by 1 dose of ChAd63-C + ChAd63-A + ChAd63-T boost, at a total dose of 1.5 x 1011 vp (5 x 1010 vp/construct) as a single IM injection of 1.0mL, using a needle and syringe. Week 0 = Prime with D-CAT Week 4 = Prime with D-CAT Week 8 = Prime with D-CAT Week 24 = Boost with ChAd63-CAT Week 28 = Controlled Human Malaria Infection (CHMI)

Biological: D/ChAd63-CAT

Infectivity Control (IC)

ACTIVE COMPARATOR

Subjects will be exposed to the bites of 5 Anopheles stephensi mosquitoes carrying infectious Pf sporozoites within a controlled clinical environment. Week 28 = Controlled Human Malaria Infection (CHMI)

Other: Infectivity Control (IC) Group

Interventions

D/ChAd63-CA BIOLOGICAL

Priming Component (DNA) = NMRC-M3V-D-PfCA (D-CA) Vaccine Boosting Component = ChAd63-PfCA

Group 1 (D/ChAd63-CA)

D/ChAd63-CAT BIOLOGICAL

Priming Component (DNA) = NMRC-M3V-D-PfCAT (D-CAT) Boosting Component = ChAd63-PfCAT

Group 2 (D/ChAd63-CAT)

Infectivity Control (IC) Group OTHER

Subjects will be exposed to bites of 5 Anopheles stephensi mosquitoes carrying infectious Pf sporozoites within a controlled clinical environment.

Also known as: Controlled Human Malaria Infection (CHMI)

Infectivity Control (IC)

Eligibility Criteria

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

You may qualify if:

• Adults (male or non-lactating, non-pregnant female) between 18 to 50 years of age at the time of enrollment
• Available and willing to participate for duration of study
• Able and willing to provide a written informed consent
• Able to complete an Assessment of Understanding (Appendix C) with a score of at least 80% correct
• In good general health with no clinically significant health problems as established by medical history, physical examination, and laboratory screening
• Men and women of childbearing potential must agree to consistently use effective means of birth control throughout the duration of the study
• Sexually active females, unless surgically sterile or at least 1 year postmenopausal, must use an effective method of avoiding pregnancy (including oral or implanted contraceptives, intrauterine device, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner) from 14 days prior to the first immunization and must agree to continue using such precautions during the study and for 6 months after the last study visit (which occurs at 90 days after CHMI).
• If female subjects are unable to bear children due to menopause or have had a procedure performed (tubal ligation or hysterectomy), a medical note from a physician is required.
• If post-menopausal, subjects must have experienced at least 1 year of amenorrhea and provide a medical note from her physician documenting this medical history.
• Sexually active men must agree to use effective means of birth control such as barrier methods (use of a condom) from the day of the first immunization and for the duration of the study (through 3 months after CHMI). Vasectomy is considered an adequate means of birth control. Men who underwent sterilization or vasectomy must provide a medical note from his physician documenting such procedure.
• Agree not to travel to a malaria endemic area during the course of the study
• Agree to refrain from blood donation during the study and for 3 years following CHMI
• Must be willing to take anti-malarial treatment after CHMI, if indicated.
• Must agree to stay in a pre-determined hotel near the NMRC CTC during the designated post-CHMI followup period from approximately 7 days after malaria challenge until antimalarial treatment is completed, if indicated

You may not qualify if:

• Weight \< 110 pounds
• Body mass index (BMI) \> 35 kg/m2
• Pregnant (positive urine pregnancy test) or nursing at screening or plans to become pregnant or nurse at any period from the time of enrollment through 6 months after the last study visit (which will occur at 90 days after CHMI).
• Receipt of any investigational malaria vaccine
• Any history of malaria infection
• Travel to a malaria endemic region within 6 months of enrollment or during the study (from enrollment through 3 months after CHMI)
• History of long-term residence (\>5 years) in an area known to have significant transmission of P falciparum (http://www.cdc.gov/malaria/map/)
• History of clinically significant contact dermatitis or sensitivity to products that contain Kathon, such as shampoos, conditioners, soaps, detergents, moisturizers, lotions, baby wipes, or cosmetics
• Positive CSP and AMA1 ELISpot assay at screening
• Positive CSP and AMA1 ELISA assay at screening
• Seropositive for the human immunodeficiency virus (HIV), hepatitis C virus (HCV), and/ or hepatitis B surface antigen (HBsAg)
• Positive sickle cell screening test, including evidence of sickle cell trait or sickle cell anemia (due to its effect on subject's susceptibility to malaria)
• History of thalassemia or thalassemia trait (due to its effect on subject's susceptibility to malaria)
• Participation in any clinical study involving another investigational vaccine, drug, or other products within 60 days prior to the first immunization or plan to participate in such a clinical study during or within 1 month following the active study phase of the study (from the day of the first immunization through 3 months after CHMI)
• Allergy to any component of the vaccine formulation or serious adverse reaction to other vaccines (such as hives, anaphylaxis, respiratory difficulty, angioedema, or abdominal pain)

Sponsors & Collaborators

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

Study Sites (2)

NMRC Clinical Trials Center

Bethesda, Maryland, 20889, United States

Location

WRAIR

Silver Spring, Maryland, 20910, United States

Location

Related Publications (7)

• Beadle C, Hoffman SL. History of malaria in the United States Naval Forces at war: World War I through the Vietnam conflict. Clin Infect Dis. 1993 Feb;16(2):320-9. doi: 10.1093/clind/16.2.320.

  PMID: 8443317 BACKGROUND

• Breman JG, Alilio MS, Mills A. Conquering the intolerable burden of malaria: what's new, what's needed: a summary. Am J Trop Med Hyg. 2004 Aug;71(2 Suppl):1-15.

  PMID: 15331814 BACKGROUND

• Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, Gilbert PB, Lama JR, Marmor M, Del Rio C, McElrath MJ, Casimiro DR, Gottesdiener KM, Chodakewitz JA, Corey L, Robertson MN; Step Study Protocol Team. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008 Nov 29;372(9653):1881-1893. doi: 10.1016/S0140-6736(08)61591-3. Epub 2008 Nov 13.

  PMID: 19012954 BACKGROUND

• Epstein JE, Rao S, Williams F, Freilich D, Luke T, Sedegah M, de la Vega P, Sacci J, Richie TL, Hoffman SL. Safety and clinical outcome of experimental challenge of human volunteers with Plasmodium falciparum-infected mosquitoes: an update. J Infect Dis. 2007 Jul 1;196(1):145-54. doi: 10.1086/518510. Epub 2007 May 29.

  PMID: 17538895 BACKGROUND

• Ogwang C, Afolabi M, Kimani D, Jagne YJ, Sheehy SH, Bliss CM, Duncan CJ, Collins KA, Garcia Knight MA, Kimani E, Anagnostou NA, Berrie E, Moyle S, Gilbert SC, Spencer AJ, Soipei P, Mueller J, Okebe J, Colloca S, Cortese R, Viebig NK, Roberts R, Gantlett K, Lawrie AM, Nicosia A, Imoukhuede EB, Bejon P, Urban BC, Flanagan KL, Ewer KJ, Chilengi R, Hill AV, Bojang K. Safety and immunogenicity of heterologous prime-boost immunisation with Plasmodium falciparum malaria candidate vaccines, ChAd63 ME-TRAP and MVA ME-TRAP, in healthy Gambian and Kenyan adults. PLoS One. 2013;8(3):e57726. doi: 10.1371/journal.pone.0057726. Epub 2013 Mar 19.

  PMID: 23526949 BACKGROUND

• Roestenberg M, O'Hara GA, Duncan CJ, Epstein JE, Edwards NJ, Scholzen A, van der Ven AJ, Hermsen CC, Hill AV, Sauerwein RW. Comparison of clinical and parasitological data from controlled human malaria infection trials. PLoS One. 2012;7(6):e38434. doi: 10.1371/journal.pone.0038434. Epub 2012 Jun 11.

  PMID: 22701640 BACKGROUND

• Verhage DF, Telgt DS, Bousema JT, Hermsen CC, van Gemert GJ, van der Meer JW, Sauerwein RW. Clinical outcome of experimental human malaria induced by Plasmodium falciparum-infected mosquitoes. Neth J Med. 2005 Feb;63(2):52-8.

  PMID: 15768480 BACKGROUND

MeSH Terms

Conditions

Malaria

Interventions

Population Groups

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Demography; Population Characteristics

Study Officials

• Nimfa Teneza-Mora, MD

  United States Military Malaria Vaccine Program, NMRC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Trial subjects will be blinded from their treatment
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: The study will include 2 vaccine groups and an infectivity control (IC) group consisting of non-immunized subjects.

Study Record Dates

• First Submitted: October 12, 2017
• First Posted: November 14, 2017
• Study Start: September 15, 2018
• Primary Completion: October 28, 2019
• Study Completion: March 23, 2020
• Last Updated: May 6, 2020

Record last verified: 2020-05

Locations

US (2)