Clinical trial NCT01717950: Safety and Immunogenicity of the Na-APR-1 Hookworm Vaccine in Healthy Adults
Official title: Phase 1 Study of the Safety and Immunogenicity of Na-APR-1 (M74)/Alhydrogel® in Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hookworm Infection
Hookworm Disease
Keywords: Human Hookworm
Necator americanus
Hookworm
Hookworm Disease
Iron-deficiency anemia
Soil-transmitted helminth infection
Neglected Tropical Disease
Na-APR-1
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: George Washington University
First posted: 2012-10-31
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Hookworms digest hemoglobin from erythrocytes for use as an energy source via a proteolytic cascade that begins with the aspartic protease, APR-1. Vaccination with recombinant APR-1 has protected animals from infection in challenge studies. This study will evaluate the safety and immunogenicity of two formulations of Na-APR-1 (M74) in healthy adult volunteers when co-administered with different concentrations of the immunostimulant GLA-AF.

Detailed description: Open-label, dose-escalation phase 1 clinical trial in healthy, hookworm-naïve adults:

* Study site: George Washington Medical Faculty Associates, Washington, DC
* Number of participants: 40 in 2 cohorts of 20.

In Cohort 1 five (5) volunteers will receive 30 µg Na-APR-1 (M74) /Alhydrogel®, five (5) will receive 30 µg Na-APR-1 (M74)/Alhydrogel® plus 2.5 µg GLA-AF, and ten (10) will receive 30 µg Na-APR-1 (M74) /Alhydrogel® plus 5 µg GLA-AF. In Cohort 2 five (5) volunteers will receive 100 µg Na-APR-1 (M74)/Alhydrogel®, five (5) will receive 100 µg Na-APR-1 (M74) /Alhydrogel® plus 2.5 µg GLA-AF, and ten (10) will receive 100 µg Na-APR-1 (M74)/Alhydrogel® plus 5 µg GLA-AF.

The cohorts will be enrolled in a staggered fashion with safety data assessed prior to the Na-APR-1 dose escalation from 30 to 100 µg. In addition, within each cohort, vaccinations will be staggered such that formulations containing 0, 2.5, and 5 µg GLA-AF will be tested sequentially: for example, those receiving Na-APR-1 (M74)/Alhydrogel® in combination with 2.5 µg GLA-AF will be vaccinated no sooner than 3 days after the last volunteer is vaccinated with the formulation containing no GLA-AF, whereas those vaccinated with Na-APR-1 (M74)/Alhydrogel® plus 5 µg GLA-AF will be vaccinated no sooner than 7 days after the last one receives the 2.5 µg GLA-AF formulation.

* Immunization schedule: Study days 0, 56 and 112.
* Route: IM in the deltoid muscle.
* Doses of Na-APR-1 (M74) to be tested: 30 and 100 µg.
* Doses of Alhydrogel®: 240 and 800 µg for the 30 and 100 µg doses of Na-APR-1 (M74), respectively.
* Doses of GLA-AF to be tested: 2.5 µg and 5 µg.
* Study duration: 44 weeks (10 months) per study participant; total duration of the study estimated at approximately 13 months.

Eligibility criteria: Inclusion Criteria:

* Males or females between 18 and 50 years, inclusive.
* Good general health as determined by means of the screening procedure.
* Available for the duration of the trial (44 weeks).
* Willingness to participate in the study as evidenced by signing the informed consent document.

Exclusion Criteria:

* Pregnancy as determined by a positive urine human choriogonadotropin (hCG) (if female).
* Participant unwilling to use reliable contraception methods up until one month following the third immunization (if female and not surgically sterile, abstinent or at least 2 years post-menopausal).
* Currently lactating and breast-feeding (if female).
* Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies.
* Known or suspected immunodeficiency.
* Laboratory evidence of liver disease (alanine aminotransferase \[ALT\] greater than 1.25-times the upper reference limit).
* Laboratory evidence of renal disease (serum creatinine greater than 1.25-times the upper reference limit, or more than trace protein or blood on urine dipstick testing).
* Laboratory evidence of hematologic disease (hemoglobin \<11.5 g/dl \[females\] or \<12.5 g/dl \[males\]; absolute leukocyte count \<3600/mm3 or \>10.7 x 103/mm3; absolute neutrophil count \[ANC\] \<1700/ mm3; absolute lymphocyte count \<700/mm3; or platelet count \<140,000/mm3).
* Laboratory evidence of a coagulopathy (PTT or PT INR greater than 1.1-times the upper reference limit).
* Serum glucose (random) greater than 1.2-times the upper reference limit.
* Other condition that in the opinion of the investigator would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol.
* Participation in another investigational vaccine or drug trial within 30 days of starting this study.
* Volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months.
* History of a severe allergic reaction or anaphylaxis.
* Severe asthma as defined by the need for daily use of inhalers or emergency clinic visit or hospitalization within 6 months of the volunteer's expected first vaccination in the study.
* Positive ELISA for hepatitis B surface antigen (HBsAg).
* Positive confirmatory test for HIV infection.
* Positive confirmatory test for hepatitis C virus (HCV) infection.
* Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of the volunteer's expected first vaccination in this study.
* Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to the volunteer's expected first vaccination in the study.
* History of a surgical splenectomy.
* Receipt of blood products within the past 6 months.
* History of previous infection with hookworm or residence for more than 6 months in a hookworm-endemic area.

Primary outcomes:
measure: Vaccine-related Adverse Events
timeFrame: Day 290
Secondary outcomes:
measure: IgG antibody response to Na-APR-1
timeFrame: 14 days after final vaccination
measure: B cell response to Na-APR-1
timeFrame: Study Days 14, 70, 126, 140 and 290
measure: Exploratory cellular immune response to Na-APR-1
timeFrame: Study Days 14, 70, 126, 140 and 290
Other outcomes:
Locations:
city: Washington
country: United States
facility: George Washington University Medical Faculty Associates
state: District of Columbia
Study officials:
affiliation: George Washington University
name: David J Diemert, MD
role: PRINCIPAL_INVESTIGATOR
References: