Sanaria™ PfSPZ Challenge Vaccine

NCT01546389 | Completed Phase 1

• 2 other identifiers: 11-0027N01AI80057C
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study will randomize 30 healthy adult participants to one of three cohorts comprised of six groups of 5 individuals per group to simultaneously receive PfSPZ Challenge via the ID route. The goal will be to determine the optimal dose required to achieve 100% infectivity (ID100) of adult volunteers with P. falciparum malaria.

Conditions

Malaria

Keywords

Malaria, vaccine, PfSPZ, challenge

Outcome Measures

Primary Outcomes (5)

• Occurrence of a positive malaria smear after the malaria challenge during a 56-day surveillance period and stratified by group.

  Days 0, 5-18, 20, 22, 24, 26, 28, 35, 42, and 56 .

• The number of serious adverse events throughout the duration of the study.

  Day 0 to1 year.

• The number and severity of solicited systemic symptoms for 14 days following ID administration of PfSPZ.

  Within 14 days after PfSPZ administration.

• The number and severity of injection site reactions within 14 days following ID administration of PfSPZ.

  Within 14 days after PfSPZ administration.

• The number and severity of unsolicited adverse events after the malaria challenge during a 56-day surveillance period (day of challenge and 55 subsequent days) but not related to malaria event symptoms.

  Days 0-56.

Secondary Outcomes (3)

• T cell responses, effector/central memory populations, and intracellular cytokine secretion (ICS) against the malaria antigens by Multiparameter Flow Cytometry

  Days 0, 5, 14 and 28

• Occurrence of a positive real-time quantitative polymerase chain reaction (PCR) after the malaria challenge during a 56-day surveillance period.

  Days 0, 5-18, 20, 22, 24, 26, 28, 35, 42, and 56.

• Antibody titers to the pre-erythrocytic stage antigens, and by indirect fluorescent antibody test for antibodies to P. falciparum sporozoites, late liver stage parasites, asexual and sexual erythrocytic stages.

  Days 0, 5, 14 and 28

Study Arms (6)

Cohort 3, Group E

EXPERIMENTAL

Cohort 3 (High Dose, Low Aliquot), Group e: 50,000 PfSPZ in 2 divided doses (e.g., 25,000 PfSPZ per 10 mcL dose); 5 subjects

Biological: Sanaria™ PfSPZ Vaccine; Drug: Chloroquine

Cohort 1, Group A

EXPERIMENTAL

Cohort 1 (Medium Dose, Medium Aliquot), Group a: 10,000 PfSPZ in 2 divided doses (e.g., 5000 PfSPZ per 50 microliter (mcL) dose); 5 subjects.

Biological: Sanaria™ PfSPZ Vaccine; Drug: Chloroquine

Cohort 1, Group B

EXPERIMENTAL

Cohort 1 (Medium Dose, Medium Aliquot), Group b: 10,000 PfSPZ in 8 divided doses (e.g., 1250 PfSPZ per 50 mcL dose); 5 subjects

Biological: Sanaria™ PfSPZ Vaccine; Drug: Chloroquine

Cohort 3, Group F

EXPERIMENTAL

Cohort 3 (High Dose, Low Aliquot), Group f: 50,000 PfSPZ in 8 divided doses (e.g., 6,250 PfSPZ per 10 mcL dose); 5 subjects

Biological: Sanaria™ PfSPZ Vaccine; Drug: Chloroquine

Cohort 2, Group D

EXPERIMENTAL

Cohort 2 (Medium Dose, Low Aliquot), Group d: 10,000 PfSPZ in 8 divided doses (e.g., 1250 PfSPZ per 10 mcL dose); 5 subjects

Biological: Sanaria™ PfSPZ Vaccine; Drug: Chloroquine

Cohort 2, Group C

EXPERIMENTAL

Cohort 2 (Medium Dose, Low Aliquot), Group c: 10,000 PfSPZ in 2 divided doses (e.g., 5000 PfSPZ per 10 mcL dose); 5 subjects

Biological: Sanaria™ PfSPZ Vaccine; Drug: Chloroquine

Interventions

Sanaria™ PfSPZ Vaccine BIOLOGICAL

30 subjects in 3 cohorts, 6 groups in different doses of PfSPZ vaccine via the intradermal route. Cohort 1 Medium Dose, Medium Aliquot: Group a: 10,000 PfSPZ in 2 divided doses (e.g., 5000 PfSPZ per 50 microliter (mcL) dose), Group b: 10,000 PfSPZ in 8 divided doses (e.g., 1250 PfSPZ per 50 mcL dose). Cohort 2: Medium dose, Low Aliquot: Group c: 10,000 PfSPZ in 2 divided doses (e.g., 5000 PfSPZ per 10 mcL dose), Group d: 10,000 PfSPZ in 8 divided doses (e.g., 1250 PfSPZ per 10 mcL dose), Cohort 3: High Dose, Low Aliquot; Group e: 50,000 PfSPZ in 2 divided doses (e.g., 25,000 PfSPZ per 10 mcL dose), Group f: 50,000 PfSPZ in 8 divided doses (e.g., 6,250 PfSPZ per 10 mcL dose)

Cohort 1, Group A; Cohort 1, Group B; Cohort 2, Group C; Cohort 2, Group D; Cohort 3, Group E; Cohort 3, Group F

Chloroquine DRUG

Rescue therapy after challenge: 1500 mg chloroquine base orally, over 48 hours (600 mg at time 0 followed by 300 mg oral base at hours 6, 24 and 48)

Cohort 1, Group A; Cohort 1, Group B; Cohort 2, Group C; Cohort 2, Group D; Cohort 3, Group E; Cohort 3, Group F

Eligibility Criteria

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

You may qualify if:

• Male or nonpregnant female between the ages of 18 and 45 years, inclusive.
• Women who are not surgically sterile (no history of bilateral tubal ligation, bilateral salpingo-oophorectomy, or hysterectomy), post-menopausal (1 year without menses) or determined otherwise by medical evaluation to be sterile must agree to practice adequate contraception (such as double barrier methods (condoms plus foam or spermicide, diaphragm plus foam or spermicide), licensed intrauterine devices (IUDs), intravaginal or intra/transdermal or oral hormonal methods initiated at least 1 month prior to inoculation or challenge, documented surgical sterilization via tubal ligation the essure procedure or hysterectomy, abstinence or a vasectomized partner). The contraceptive method should remain unchanged throughout the entire study period (56 days). Serologic pregnancy tests will be conducted upon screening. Urine testing will be done on the day of malaria challenge, on the day of the first positive malaria smear and at the conclusion of active surveillance (Day 56).
• Is in good health, as determined by vital signs (heart rate, blood pressure, oral temperature), medical history, screening 12-lead ECG and a physical examination.
• Has normal laboratory values (Urinalysis (assessing blood, and protein presence as greater than trace by dipstick), hemoglobin, WBC, platelet count, AST, ALT, bilirubin, glucose, and creatinine) prior to challenge study. Any abnormal screening value for any screening test listed in Table 8 will exclude the participant from the study with the exception of elevated fasting glucose and hematuria \>1+ detected during menses for females. Elevated fasting glucose may need to be repeated due to recent carbohydrate consumption and is therefore not a true fasting glucose. Subsequent repeat fasting glucose testing that is in the normal range will be acceptable for participation. For females who are menstruating, urinalysis frequently tests positive for blood and is not an indicator of poor health status or increased risk. This can be repeated if clinically warranted.
• Able to understand and comply with planned study procedures including an inpatient stay from Day 8-18 after malaria challenge.
• Provides informed consent prior to any study procedures, correctly answers \> 70% on the post consent quiz and is available for all study visits.
• Willing to avoid non-study related blood donation for 3 years

You may not qualify if:

• Has any known history of malaria infection, is a long-term resident (\> 5 years) of a malaria-endemic area, was born and resided in a malaria-endemic area, or has traveled to a malaria-endemic area within the previous 6 months.
• Has a positive urine pregnancy test prior to malaria challenge (if female of childbearing potential), is lactating, or has the intention to become pregnant within 2 months after enrollment in this study.
• Use of any antibiotic (that has known or potential antimalarial properties) or antimalarial drug beginning 28 days prior to the screening and extending to Day 56 of study surveillance.
• Has evidence of increased cardiovascular disease risk (defined as \> 10%, 5 year risk) as determined by the method of Gaziano. Risk factors include sex, age (years), systolic blood pressure (mm Hg), smoking staus (current vs. past or never), BMI (kg/mm2), reported diabetes status (yes/no), current treatment for raised blood pressure (yes/no).
• Is immunosuppressed (e.g., poorly-controlled diabetes mellitus, cirrhosis, renal insufficiency, active malignancy, connective tissue disease, organ transplant) as a result of an underlying illness or treatment.
• An abnormal ECG, defined as one showing pathologic Q waves and significant ST-T wave changes; left ventricular hypertrophy; any non-sinus rhythm excluding isolated premature atrial contractions; right or left bundle branch block; or advanced (secondary or tertiary) A-V heart block.
• Has an active neoplastic disease (excluding nonmelanotic skin cancer) or neoplastic disease within the past 5 years or any history of hematologic malignancy.
• Has a known history of human immunodeficiency virus, hepatitis B surface antigen positivity, or Hepatitis C infection.
• Has a history of alcohol or drug abuse in the last 5 years.
• Has a history of receiving blood products within the 3 months prior to enrollment in this study.
• Has a history of psoriasis or porphyria, which may be exacerbated after treatment with chloroquine.
• Has an acute or chronic medical condition that, in the opinion of the investigator, would render malaria challenge unsafe or would interfere with the evaluation of responses (this includes, but is not limited to: known liver disease, renal disease, neurological disorders, visual field defects, cardiac disorders, pulmonary disorders, auditory damage, diabetes mellitus, and transplant recipients).
• Has a history of anaphylactic response to mosquito bites or known allergy to chloroquine, 4-aminoquinoline derivatives, atovaquone/proguanil, (Malarone®), ibuprofen, or acetaminophen that may be used to treat volunteers developing malaria after P. falciparum challenge.
• Is using or intends to continue using a medication known to cause drug reactions with chloroquine or Malarone®, such as cimetidine, metoclopramide, antacids or kaolin (antacids and kaolin can be administered at least 4 hours from intake of chloroquine).
• History of retinal or visual field changes, auditory damage, or seizures.

Sponsors & Collaborators

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

Study Sites (1)

University of Maryland School of Medicine - Center for Vaccine Development - Baltimore

Baltimore, Maryland, 21201-1509, United States

Location

Related Publications (1)

• Lyke KE, Laurens MB, Strauss K, Adams M, Billingsley PF, James E, Manoj A, Chakravarty S, Plowe CV, Li ML, Ruben A, Edelman R, Green M, Dube TJ, Sim BKL, Hoffman SL. Optimizing Intradermal Administration of Cryopreserved Plasmodium falciparum Sporozoites in Controlled Human Malaria Infection. Am J Trop Med Hyg. 2015 Dec;93(6):1274-1284. doi: 10.4269/ajtmh.15-0341. Epub 2015 Sep 28.

  PMID: 26416102 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
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2011
• First Posted: March 7, 2012
• Study Start: April 1, 2012
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: September 13, 2013

Record last verified: 2013-09

Locations

US (1)