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Phase I Study of AMA1-C1/Alhydrogel® (Registered Trademark) + CPG 7909 Malaria Vaccine

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00427167
First received: January 25, 2007
Last updated: August 27, 2009
Last verified: August 2009
  Purpose

This study will evaluate the safety and immune response of healthy volunteers to an experimental malaria vaccine called AMA1-C1/Alhydrogel® (Registered Trademark) + CPG 7909. Malaria is an infection of red blood cells caused by a parasite, Plasmodium falciparum, that is spread by certain kinds of mosquitoes. Each year, about 1 million people are killed by malaria worldwide, most of them young children in Africa. AMA1 C1 may help block the malaria parasite from getting into red blood cells. The vaccine is mixed with Alhydrogel® (Registered Trademark), a material that is commonly added to vaccines to make them work better (also called an adjuvant). Besides evaluating the vaccine, this study will also test two solutions of an experimental adjuvant, CPG 7909-P and CPG 7909-S.

Healthy people between 18 and 50 years of age may be eligible for this 7-month study. Participants are randomly assigned to one of four treatment groups (A, B, C or D below). All receive two vaccinations, given as a shot in the upper arm either 1 or 2 months apart, as shown:

  • Group A: AMA1 CI/Alhydrogel® (Registered Trademark)/CPG 7909-P at Day 0 and Day 28 (1-month interval)
  • Group B: AMA1 CI/Alhydrogel® (Registered Trademark)/CPG 7909-S at Day 0 and Day 28 (1-month interval)
  • Group C: AMA1 CI/Alhydrogel® (Registered Trademark)/CPG 7909-P at Day 0 and Day 56 (2-month interval)
  • Group D: AMA1 CI/Alhydrogel® (Registered Trademark)/CPG 7909-S at Day 0 and Day 56 (2-month interval)

Group A and B participants return to the clinic for checkups at 3, 7, and 14 days after each vaccination and again at months 2, 3, 4, 5, and 7. Group C and D participants come to the clinic at 3, 7, and 14 days after each vaccination and again at months 3, 4, 5, and 7.

In addition to the vaccinations, the study includes the following procedures:

  • Photographs of the subject's arm where the vaccination is given if a rash develops.
  • Daily temperature and symptoms record for the first 6 days after each of the 2 vaccinations, and at any other time there is concern about fever or other symptoms.
  • Blood draws about 12 times during the study to check for safety and to measure the antibody response and the effect of the study vaccine.

Some participants may be asked to undergo plasmapheresis, a procedure for collecting plasma, the liquid part of the blood. This is done by using a machine called a blood cell separator. Blood is collected through a needle place...


Condition Intervention Phase
Malaria
Biological: AMA1-C1/Alhydrogel + CPG 7909 (Saline)
Biological: AMA1-C1/Alhydrogel + CPG 7909 (Phosphate)
Drug: AMA1-C1/Alhydrogel + CPG 7909
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: Phase I Study of the Safety and Immunogenicity of AMA1-C1/Alhydrogel + CPG 7909, an Asexual Blood Stage Vaccine for Plasmodium Falciparum Malaria

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Assessment of the safety and reactogenicity of the AMA1-C1/Alhydrogel + CPG 7909 vaccine in phosphate and saline buffers; and determine the frequency of summarized systemic and local AFs by severity and relationship to the vaccine.

Secondary Outcome Measures:
  • Demonstrate that the immune responses to AMA1-C1 7909 in a saline buffer are not inferior to the immune responses to AMA-C1 + CPG 7909 in a phosphate buffer.

Estimated Enrollment: 300
Study Start Date: January 2007
Study Completion Date: November 2008
Primary Completion Date: November 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: AMA1-C1/Alhydrogel + CPG 7909 (Saline)
    N/A
    Biological: AMA1-C1/Alhydrogel + CPG 7909 (Phosphate)
    N/A
    Drug: AMA1-C1/Alhydrogel + CPG 7909
    N/A
Detailed Description:

AMA1-C1 + CPG 7909 is a blood stage malaria vaccine candidate. The objectives of this Phase 1 study are to confirm the previously demonstrated safety and immunogenicity of AMA1-C1 + CPG 7909 formulated in a phosphate buffer. In addition, this study will evaluate the safety and immunogenicity of AMA1-C1 + CPG 7909 formulated in a saline buffer, and determine if the addition of CPG 7909 in a saline buffer enhances the immune response to AMA1-C1 in a manner similar to that seen with the addition of CPG 7909 in a phosphate buffer. The immunological effect of giving a second dose of vaccine at 1 or 2 months will also be evaluated. The study is a double blind Phase 1 clinical trial in healthy adult volunteers. Volunteers will be screened and 24 participants will be enrolled and randomly assigned to 1 of 4 groups in a 2x2 design: 6 volunteers will receive 2 doses of 80 micrograms AMA1-C1/Alhydrogel + 500 micrograms CPG 7909 (phosphate) at a 1-month dosing interval; 6 volunteers will receive 2 doses of 80 micrograms AMA1-C1/Alhydrogel + 500 micrograms CPG 7909 (saline) at a 1 month dosing interval; 6 volunteers will receive 2 doses of 80 micrograms AMA1-C1/Alhydrogel + 500 micrograms CPG 7909 (phosphate) at a 2-month dosing interval; and 6 volunteers will receive 2 doses of 80 micrograms AMA1-C1/Alhydrogel + 500 micrograms CPG 7909 (saline) at a 2 month dosing interval. Safety outcome measures are local and systemic (including laboratory) adverse events. Immune responses to vaccination will be measured by enzyme-linked immunosorbent assay (ELISA) and parasite growth inhibition assay (GIA), and will be compared among groups.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

Age between 18 and 50 years, inclusive.

Good general health as determined by review of medical history and/or clinical tests at screening.

Available for the duration of the trial (30 weeks).

Willingness to participate in the study as evidenced by signing the informed consent document.

EXCLUSION CRITERIA:

  1. Pregnancy as determined by a positive urine beta-hCG at any time during the study (if female).
  2. Participant unwilling to use reliable contraception methods for at least 2 weeks prior to vaccination and for the duration of the trial. Reliable methods of birth control include: pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with spermicide; surgical sterilization; vaginal ring; intrauterine device; abstinence; and post-menopause (if female).
  3. Currently breast-feeding (if female).
  4. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and cooperate with the study protocol.
  5. Neutropenia as defined by an absolute neutrophil count less than 1500/mm(3).
  6. Alanine aminotransaminase (ALT) level above the laboratory-defined upper limit of normal.
  7. Serum creatinine level above the laboratory-defined upper limit of normal.
  8. Hemoglobin below the laboratory-defined lower limit of normal, by sex.
  9. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
  10. Other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant participating in the trial or would render the subject unable to comply with the protocol.
  11. History of receiving any investigational product within the past 30 days.
  12. Participant has had medical, occupational or family problems as a result of alcohol or illicit drug use during the past 12 months.
  13. History of a severe allergic reaction or anaphylaxis.
  14. Positive ELISA and confirmatory Western blot tests for HIV-1.
  15. Positive ELISA and confirmatory immunoblot tests for hepatitis C virus (HCV).
  16. Positive hepatitis B surface antigen (HBsAg) by ELISA.
  17. Pre-existing autoimmune or antibody-mediated diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, or autoimmune thrombocytopenia.
  18. Known immunodeficiency syndrome.
  19. Positive serum anti-dsDNA titer.
  20. Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study.
  21. Receipt of a live vaccine within past 4 weeks or a killed vaccine within past 2 weeks prior to entry into the study.
  22. History of a surgical splenectomy.
  23. Receipt of blood products within the past 6 months.
  24. Previous receipt of an investigational malaria vaccine.
  25. Receipt of antimalarial prophylaxis during the past 12 months, or receipt of chloroquine or related compounds (amodiaquine or primaquine) in the previous 8 weeks prior to study entry.
  26. Prior malaria infection.
  27. Any medical, psychiatric, social, or occupational condition or other responsibility that, in the judgment of the Principal Investigator (PI), would interfere with the evaluation of study objectives.
  28. History of a known allergy to nickel.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00427167

Locations
United States, District of Columbia
Johns Hopkins University Bloomberg School of Public Health
Washington, District of Columbia, United States, 20037
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00427167     History of Changes
Other Study ID Numbers: 070083, 07-I-0083
Study First Received: January 25, 2007
Last Updated: August 27, 2009
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Blood Stage
Investigational
Vaccine
Malaria
Healthy Volunteer
HV

Additional relevant MeSH terms:
Malaria
Parasitic Diseases
Protozoan Infections
Aluminum Hydroxide
Adjuvants, Immunologic
Antacids
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014