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MalariaPhase 1NCT03341754

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

A Phase 1 study testing D/ChAd63-CA and D/ChAd63-CAT in people with Malaria, run by U.S. Army Medical Research and Development Command at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Malaria
What is being tested?
D/ChAd63-CA and D/ChAd63-CAT
Could I receive a placebo?
No, everyone receives an active treatment
How many people
52 participants
Where
2 sitesUnited States
Study dates
15 Sep 2018to 23 Mar 2020
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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)
Show all 35Show fewer
  • 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)
  • History of a severe and/or anaphylactic response to mosquito-bites
  • Known allergy to chloroquine phosphate, atovaquone/proguanil, or artemether/lumefantrine, which will be used to treat subjects who may develop malaria after Plasmodium falciparum challenge
  • History of psoriasis (given its interaction with chloroquine)
  • History of porphyria
  • History of hemolytic anemia
  • Use or planned use of any drugs with significant anti-malarial activity, such as doxycycline, clindamycin, azithromycin, or trimethoprim/sulfamethoxazole among others that would coincide with periods of CHMI or post-CHMI followup
  • Has evidence of increased cardiovascular disease risk (> 5%-10%, 5-year risk)
  • As determined by the method of Gaziano et al (2008, Appendix D)
  • Risk factors include sex, age (years), smoking status, body mass index (BMI, kg/m2), presence or absence of diabetes mellitus, and blood pressure.
  • An abnormal EKG, defined as one showing Q waves and/or significant ST-T wave changes, left ventricular hypertrophy, any non-sinus rhythm (excluding isolated premature atrial contraction), right or left bundle branch block, or advanced (secondary or tertiary) A-V heart block
  • Current or chronic use of systemic immunosuppressant pharmacotherapy or immunomodulators; however, subjects may be allowed to use inhaled steroids or topical steroids.
  • History of splenectomy (given its effects on immunity to malaria)
  • Receipt of immunoglobulins and/or any blood products within 90 days of scheduled immunization
  • History of neurologic disorder (including seizures or migraine headache)
  • History of cancer (except for basal cell carcinoma of the skin)
  • Current significant medical condition (cardiovascular, pulmonary, hepatic, renal, or hematological) or evidence of any other serious underlying medical condition identified by medical history, physical examination, or laboratory screening tests
  • History of any other illness or condition which, in the investigator's judgment, may substantially increase the risk associated with the subject's participation in the protocol or compromise the scientific objectives. This may include psychiatric disorders (such as personality disorders, anxiety disorders, major depressive disorder or schizophrenia) or behavioral tendencies (including active alcohol or drug abuse) discovered during the screening process that in the opinion of the investigator would make compliance with the protocol difficult
  • Plan for surgery during the study (from enrollment until 3 months post-CHMI) with the exception of minor cutaneous procedures
  • Females who are pregnant or nursing, or plan to become pregnant or nurse during the study period (from enrollment through 3 months post CHMI) or within 6 months after the last study visit
  • Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study or compromise the scientific objectives

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • NMRC Clinical Trials Center

    Bethesda, Maryland, 20889

  • WRAIR

    Silver Spring, Maryland, 20910

Other trials in United States

About this study

Official title: A Phase 1 Trial With Controlled Human Malaria Infection to Evaluate the Safety, Immunogenicity, and Protective Efficacy of Two-Antigen and Three-Antigen Plasmodium Falciparum DNA Prime-Adenovirus Boost Malaria Vaccine Regimens in Healthy Malaria Naïve Adults

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.

Read the detailed description

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. Approximately 4 weeks after administration of the boosting immunization the vaccinated groups and the IC group will participate in CHMI wherein subjects will be exposed to the bites of 5 Anopheles stephensi mosquitoes carrying infectious Pf sporozoites within a controlled clinical environment. Protection will be determined by the examination of thick blood smears through 28 days post-CHMI and by retrospective PCR analysis for the presence of blood stage parasites. All groups will be enrolled and evaluated in one cohort. Due to a limit in the number of subjects who can undergo malaria challenge at the facility in one day, CHMI will be conducted over two days.

Group 1 (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.

Group 2 (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-freeinjection 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.

Conditions
Malaria
Being tested
D/ChAd63-CA, D/ChAd63-CAT, Infectivity Control (IC) Group
Keywords
Malaria Infection
Medical subject headings
Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • D/ChAd63-CABiological

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

  • D/ChAd63-CATBiological

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

  • Infectivity Control (IC) GroupOther

    Also called Controlled Human Malaria Infection (CHMI)

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

Study groups in NCT03341754
Study groupRoleWhat they receive
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)
Receives: 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)
Receives: Biological: D/ChAd63-CAT
Infectivity Control (IC)Active comparatorSubjects 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)
Receives: Other: Infectivity Control (IC) Group

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Occurrence of Serious Adverse Events

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

    Measured: Through day 7 after each immunization

  2. 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

    Measured: Through day 28 after each immunization

  3. Occurrence of Abnormal Laboratory Values

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

    Measured: Through day 28 after each immunization

  4. 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

    Measured: Enrollment through 3 months after CHMI

Secondary outcomes (4)

  1. Vaccine Efficacy Determined by Time to Development of Parasitemia

    Vaccine Efficacy Determined by Time to Development of Parasitemia as measured by microscopic examination of thick smears and by Polymerase Chain Reaction (PCR) after CHMI and PCR analysis conducted retrospectively

    Measured: after CHMI: Days 7 - 28

  2. Measurement of Antibody Titers Against Sporozoite and Erythrocyte Stage Parasites

    Measurement of antibody titers against sporozoite and erythrocyte stage parasites by immunofluorescence assay (IFA) using sera/plasma

    Measured: Days 231 and 286

  3. 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

    Assess the association between the subjects' pre-immunization neutralizing antibody titers to HuAd5 and the protective efficacy and humoral and cellular immunogenicity, of these prime-boost regimens to CSP, AMA1 and TRAP as measured by ELISA and FluoroSpot assays

    Measured: 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

  4. Comparison of Immunogenicity of the 2 Vaccine Regimens

    Comparison of immunogenicity,of the 2 heterologous prime-boost vaccine regimens (D/ChAd63-CA vs. D/ChAd63-CAT

    Measured: Days 1 - 286

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Nov 2017
  2. Study start15 Sep 2018
  3. Primary completion28 Oct 2019
  4. Study completion23 Mar 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Model description
The study will include 2 vaccine groups and an infectivity control (IC) group consisting of non-immunized subjects.
Masking
Single blind
Who is masked
Participant
Enrolment
52 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03341754
Sponsor's protocol ID
S-14-07
Other IDs
NMRC.2016.0006, NavOx
Status last verified
May 2020
First submitted
12 Oct 2017
Last updated
6 May 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 8443317

  • 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.

    PubMed 15331814

  • 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.

    PubMed 19012954

  • 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.

    PubMed 17538895

  • 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.

    PubMed 23526949

  • 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.

    PubMed 22701640

  • 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.

    PubMed 15768480

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing D/ChAd63-CA and D/ChAd63-CAT in people with Malaria, run by U.S. Army Medical Research and Development Command at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 May 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Occurrence of Serious Adverse Events (time frame: Through day 7 after each immunization). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03341754, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2020.

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Clinical Trial NCT03341754 | AzTrials