EBA-175 RII-NG Malaria Vaccine Administered Intramuscularly in Semi-immune Adults

NCT01026246 | Completed Phase 1

• 1 other identifier: 08-0009
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Malaria is caused by a germ that people get from the bites of some mosquitoes. It kills over 2 million people each year. Many of the drugs used to treat malaria do not work as well as they used to and researchers are exploring other vaccines to prevent malaria. The purpose of this study is to learn if the vaccine, called EBA-175 RII-NG, is safe and if it strengthens the body's defenses against malaria. Participants will include 60 healthy adults, ages 18-40, recruited from Accra, Ghana. Several dosages of the vaccine will be tested for safety. The lowest dosages of the vaccine will be tested before the next higher dose is tested. There will be two groups for each dose, one group will receive the vaccine and the other group will receive a placebo (salt water solution). Participants may be involved in study related procedures for up to 398 days.

Conditions

Plasmodium Falciparum Malaria

Keywords

Ghana, malaria, vaccine, Plasmodium falciparum

Outcome Measures

Primary Outcomes (5)

• Number of subjects experiencing severe (Grade 3) solicited injection site reactions.

  Within 14 days following vaccination.

• Number of subjects experiencing severe solicited systemic reactions (Grade 3).

  Within 14 days following vaccination.

• Number of subjects experiencing severe (Grade 3) clinical laboratory values.

  Within 14 days following vaccination.

• Number of subjects spontaneously reporting adverse events considered associated with the vaccination that are severe (Grade 3).

  Duration of study.

• Serious adverse events considered associated with the vaccination.

  Duration of study.

Secondary Outcomes (4)

• Number of subjects experiencing a 4-fold increase in Anti-EBA-175 RII-NG antibody level (ELISA).

  Days 14, 28, 42, 180 and 194 relative to baseline.

• Relative binding inhibition of recombinant EBA-175 RII-NG to human red blood cells in vitro in the presence of serum from immunized individuals.

  Days 0, 14, 28, 42, 180 and 194.

• Anti-EBA-175 RII-NG antibody level by enzyme-linked immunosorbent assay (ELISA).

  Days 0, 14, 28, 42, 180 and 194.

• Relative growth inhibition of Plasmodium falciparum in human red blood cells cultured in vitro in the presence of serum from immunized individuals.

  Days 0, 14, 28, 42, 180 and 194.

Study Arms (3)

Group B: 20 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant

EXPERIMENTAL

18 subjects to receive 20 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant; 2 subjects to receive placebo.

Drug: Placebo; Biological: EBA-175 RII-NG Malaria Vaccine

Group A: 5 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant

EXPERIMENTAL

18 subjects to receive 5 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant; 2 subjects to receive placebo.

Drug: Placebo; Biological: EBA-175 RII-NG Malaria Vaccine

Group C: 80 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant

EXPERIMENTAL

18 subjects to receive 80 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant; 2 subjects to receive placebo.

Drug: Placebo; Biological: EBA-175 RII-NG Malaria Vaccine

Interventions

Placebo DRUG

The placebo used will be normal saline (0.9 percent NaCl).

Group A: 5 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant; Group B: 20 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant; Group C: 80 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant

EBA-175 RII-NG Malaria Vaccine BIOLOGICAL

EBA-175 RII-NG malaria vaccine is supplied as a white, translucent, cloudy, nonparticulate liquid suspension in single-dose clear glass vials pre-mixed with Adju-Phos aluminum phosphate adjuvant. Each 2-mL vial of EBA-175 RII-NG vaccine contains: 0.7 mL (0.5 mL per dose) EBA-175 RII-NG, at the required dose concentration, 5 percent sucrose, 1.0 mg/mL (0.5 mg/0.5 mL per dose) aluminum as aluminum phosphate adjuvant, sodium phosphate buffer (10 mM sodium phosphate and 150 mM sodium chloride), and no preservative.

Group A: 5 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant; Group B: 20 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant; Group C: 80 mcg EBA-175 + 500 mcg aluminum phosphate adjuvant

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males and healthy non-pregnant and non breastfeeding females between the ages of 18 and 40 years.
• Females of childbearing potential must agree to practice adequate contraception through out the study and for 3 months after the third vaccination (including abstinence; hormonal contraception; condoms with spermicidal agents); males with female partners of childbearing age must agree to use condoms or other birth control.
• Good health as determined by screening medical history, physical examination (PE), and routine laboratory assessments.
• Willingness to comply with protocol requirements.
• Ability to provide informed consent before any protocol procedures are performed.
• Availability for follow-up for 12 months after the first immunization dose.

You may not qualify if:

• Regular use of medications other than vitamins and contraceptives.
• Current or recent (within the last 4 weeks prior to vaccination) treatment with parenteral, inhaled, or oral corticosteroids (intranasal steroids are acceptable), or other immunosuppressive agents, or chemotherapy.
• History of splenectomy.
• Abnormal screening laboratory values. Any abnormal screening value for any screening test, will exclude the subject from the study. An exception to this rule is the glucose measurement. Random plasma glucose will be measured on all subjects during the screening visit. Values higher than 110 mg/dl will be confirmed by a repeat fasting glucose measurement.
• History of or current medical, occupational, social or family problems as a result of alcohol or illicit drug use by the volunteer.
• History of moderate to severe mental illness, as defined by symptoms interfering with social or occupational function or suicidal thoughts/attempts.
• History of receiving blood or blood products (such as blood transfusion, platelet transfusion, immunoglobulins, hyperimmune serum) in the previous 6 months.
• Vaccination with a live vaccine within the past 30 days or with a non-replicating, inactivated, or subunit vaccine within the last 14 days.
• Known hypersensitivity to components of the vaccine \[Erythrocyte-Binding Antigen 175 kDa Region II-Nonglycosylated (EBA-175 RII-NG), sucrose, or aluminum adjuvant\].
• History of acute or chronic medical conditions including, but not limited to, disorders of the liver, kidney, lung, heart, or nervous system, or other metabolic and autoimmune/inflammatory conditions, sickle cell disease.
• History of anaphylaxis or severe hypersensitivity reaction.
• Severe asthma, as defined by an emergency room visit or hospitalization within the last 12 months.
• Pregnant or breastfeeding women, or women unwilling to use effective contraception during the study period.
• Acute illness, including temperature \> 37.8 degrees Celsius within one week prior to vaccination.
• Positive serology for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B surface antigen (HBsAg).

Sponsors & Collaborators

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

Study Sites (1)

Noguchi Memorial Institute for Medical Research - Immunology

Legon, Greater Accra Region, Ghana

Location

Related Publications (1)

• Koram KA, Adu B, Ocran J, Karikari YS, Adu-Amankwah S, Ntiri M, Abuaku B, Dodoo D, Gyan B, Kronmann KC, Nkrumah F. Safety and Immunogenicity of EBA-175 RII-NG Malaria Vaccine Administered Intramuscularly in Semi-Immune Adults: A Phase 1, Double-Blinded Placebo Controlled Dosage Escalation Study. PLoS One. 2016 Sep 19;11(9):e0163066. doi: 10.1371/journal.pone.0163066. eCollection 2016.

  PMID: 27644034 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Condition Hierarchy (Ancestors)

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

Study Design

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

Study Record Dates

• First Submitted: December 3, 2009
• First Posted: December 4, 2009
• Study Start: June 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: March 29, 2013

Record last verified: 2012-05

Locations

GH (1)