PfSPZ Challenge in Healthy Malaria-Naïve Adults in the United States

NCT02773979 | Completed Phase 1 FDA Drug

• 2 other identifiers: 11-0042HHSN272201300019I
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial of the replication-intact PfSPZ Challenge vaccine given under CQ cover will enroll 28 healthy volunteers to receive PfSPZ or placebo, as well as suppressive doses of chloroquine (CQ)on varying schedules. 10 weeks post 3rd immunization subjects will be subjected to controlled human malarial infection. The primary objective of this study is to evaluate the safety and tolerability of escalating doses of Sanaria PfSPZ Challenge administered by DVI on varying schedules to healthy malaria-naïve adults taking suppressive doses of CQ (PfSPZ-CVac).

Conditions

Plasmodium Falciparum Infection

Keywords

challenge; malaria; P. falciparum; PfSPZ; sporozoites; vaccine

Outcome Measures

Primary Outcomes (7)

• The number of serious adverse events (SAEs) related to study product.

  Days 1-203

• The number of solicited local adverse events (AEs)

  Days 1-93

• The number of solicited systemic adverse events(AEs)

  Day 1-116

• The number of unsolicited adverse events (AEs) related to study product

  Days 1-130

• The severity of solicited local adverse events (AEs) as assessed by grading scales

  Day 1-93

• The severity of solicited systemic adverse event (AEs) as assessed by grading scales

  Day 1-116

• The severity of unsolicited AEs related to study product as assessed by grading scales.

  Days 1-130

Study Arms (3)

Group 1: PfSPZ 51200 sporozoites/Placebo

ACTIVE COMPARATOR

Chloroquine (CQ)/PfSPZ Challenge 51200 sporozoites or CQ/normal saline (NS). N=12, randomized 3:1

Drug: Chloroquine; Biological: PfSPZ (NF54) Challenge; Other: Placebo

Group 2: PfSPZ 102400 sporozoites/Placebo

ACTIVE COMPARATOR

CQ/PfSPZ Challenge 102400 sporozoites or CQ/NS. N=4, randomized 3:1

Drug: Chloroquine; Biological: PfSPZ (NF54) Challenge; Other: Placebo

Group 3: PfSPZ 102400 sporozoites

ACTIVE COMPARATOR

CQ/PfSPZ Challenge 102400 sporozoites N=9

Drug: Chloroquine; Biological: PfSPZ (NF54) Challenge

Interventions

Chloroquine DRUG

Administered as 600mg PO, day 1, 300mg PO days 8, 15, 22.

Group 1: PfSPZ 51200 sporozoites/Placebo; Group 2: PfSPZ 102400 sporozoites/Placebo; Group 3: PfSPZ 102400 sporozoites

PfSPZ (NF54) Challenge BIOLOGICAL

Cryopreserved Plasmodium falciparum (Pf) fully infectious sporozoites (SPZ) that have been developed to be used to infect volunteers in controlled human malaria infection (CHMI) to assess the efficacy of antimalarial drugs and vaccines. The PfSPZ (NF54) Challenge contains a laboratory malaria strain isolated from a Dutch traveler to Africa.

Group 1: PfSPZ 51200 sporozoites/Placebo; Group 2: PfSPZ 102400 sporozoites/Placebo; Group 3: PfSPZ 102400 sporozoites

Placebo OTHER

Placebo

Group 1: PfSPZ 51200 sporozoites/Placebo; Group 2: PfSPZ 102400 sporozoites/Placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adults (males and non-pregnant, non-lactating females) between the ages of 18 and 45 years, inclusive.
• Able and willing to participate for the duration of the study.
• Able and willing to provide written (not proxy) informed consent.
• Provides informed consent before any study procedures, correctly answers \>/= 70% of questions on the post consent quiz and is available for all study visits.
• Women of childbearing potential\* must have a negative serum pregnancy test at screening and a negative urine pregnancy test prior to each vaccination and on the day of malaria challenge.
• Not sterilized via bilateral tubal ligation, bilateral oophorectomy, hysterectomy, or menopausal and still menstruating or \< 1 year of the last menses.
• Women of childbearing potential must have used an acceptable method of contraception\* in the 30 days prior to enrollment and must agree to continue use of the same method throughout the study.
• Includes, but is not limited to, abstinence from sex with men, monogamous relationship with vasectomized partner who has been vasectomized for 6 months or more prior to enrollment, barrier methods such as condoms or diaphragms with spermicide or foam, effective intrauterine devices, NuvaRing, successful Essure placement (permanent, non-surgical, non-hormonal sterilization) with documented confirmation test at least 3 months after the procedure, and licensed hormonal methods such as implants, injectables, or oral contraceptives.
• Is in good health, as judged by the investigator, and determined by vital signs (heart rate, blood pressure, and oral temperature), medical history and physical examination.
• Able to understand and comply with planned study procedures.
• Reachable (24/7) by mobile phone during the whole study period and willing to provide two close contacts to assist with making contact.
• Lives in the greater Seattle area and within an approximately one hour commute to the study research clinic.
• Willing to avoid non-study related blood donation for 3 years following P. falciparum challenge.
• Agrees not to travel to a malaria endemic region during the entire course of the trial.
• Agrees not to travel away from the greater Seattle area from the day of first study immunization through 20 days after the last study immunization, and during the 29 days after CHMI.

You may not qualify if:

• History of malaria infection or vaccination, residence in a malaria-endemic area for \> / =5 years, travel to a malaria-endemic area in the past 6 months, or participation in a malaria research study.
• Is breastfeeding or plans to breastfeed at any time throughout the study.
• Plans to become pregnant at any time throughout the study.
• Use of any antimalarial antibiotic or drug within 28 days prior to Study Day 1 or planned use during the study period.
• Any clinically significant acute or chronic medical condition\* or need for chronic medications\*\* that, in the opinion of the investigator, will interfere with immunity or affect safety.
• Includes, but is not limited to, disorders of the liver, kidney, lung, heart, or nervous system, or other metabolic or autoimmune/inflammatory conditions.
• Receipt of systemic, prescription medications for the treatment of chronic medical conditions or variations of normal physiologic functions are permissible if, in the opinion of the investigator, they are used for conditions that are not clinically significant and would not impact the effectiveness of the vaccine or the safety of the subject or the safety and immunogenicity outcomes of the protocol. Use of systemic, over-the-counter medications and PRN systemic, prescription medications are allowed if, in the opinion of the investigator, they pose no additional risk to subject safety, vaccine efficacy or assessment of immunogenicity/reactogenicity. Topical (except corticosteroid) medications, nasal (including corticosteroid) medications, vitamins, and supplements are permissible. Any drug with antimalarial properties is not permissible.
• Asthma, other than mild, well-controlled asthma\*.
• Cold or exercise induced asthma controlled with inhaled medications other than inhaled corticosteroids is permissible. Subjects should be excluded if they require daily bronchodilator use, or have had an asthma exacerbation requiring oral/parenteral steroid use or have used theophylline or inhaled corticosteroids in the past year.
• Diabetes mellitus.
• History of a psychiatric condition that may make study compliance difficult, such as schizophrenia, or unstable bipolar disorder\*.
• Includes persons with psychoses or history of suicide attempt or gesture in the 3 years before study entry or an ongoing risk for suicide.
• Any history of non-febrile seizures or complex febrile seizures\*
• Autoimmune disease (autoimmune thyroid disease is permissible and vitiligo or mild eczema not requiring chronic therapy is permissible).
• Abuse of alcohol or drugs that, in the opinion of the investigator, may interfere with the subject's ability to comply with the protocol.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Kaiser Permanente Washington Health Research Institute - Vaccines and Infectious Diseases

Seattle, Washington, 98101-1466, United States

Location

Related Publications (1)

• Murphy SC, Deye GA, Sim BKL, Galbiati S, Kennedy JK, Cohen KW, Chakravarty S, Kc N, Abebe Y, James ER, Kublin JG, Hoffman SL, Richie TL, Jackson LA. PfSPZ-CVac efficacy against malaria increases from 0% to 75% when administered in the absence of erythrocyte stage parasitemia: A randomized, placebo-controlled trial with controlled human malaria infection. PLoS Pathog. 2021 May 28;17(5):e1009594. doi: 10.1371/journal.ppat.1009594. eCollection 2021 May.

  PMID: 34048504 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

Chloroquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2016
• First Posted: May 16, 2016
• Study Start: September 12, 2016
• Primary Completion: January 22, 2018
• Study Completion: January 22, 2018
• Last Updated: December 27, 2019

Record last verified: 2017-04-05

Locations

US (1)