Plasmodium Falciparum MalariaPhase 1NCT00344539
AMA1-C1/Alhydrogel + CpG 7909 for Malaria
A Phase 1 study testing AMA1-C1/Alhydrogel® and CPG 7909 Oligodeoxynucleotide (VaxImmune®) in people with Plasmodium Falciparum Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
The purpose of this study is to test an experimental malaria vaccine in about 75 healthy adults, 18-45 years of age. The study will also test an experimental adjuvant which is a material added to a vaccine to help the body make more defense cells. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Plasmodium Falciparum Malaria
- What is being tested?
- AMA1-C1/Alhydrogel® and CPG 7909 Oligodeoxynucleotide (VaxImmune®)
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- May 2005to Jan 2007
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age between 18 and 45 years, inclusive.
- Good general health as a result of review of medical history and/or clinical tests.
- Available for the duration of the trial (34 weeks).
- Willingness to participate in the study as evidenced by signing the informed consent document.
Who cannot join
- Pregnancy as determined by a positive urine Beta-hCG (if female) at any point during the study.
- Participant unwilling to use highly effective contraception methods (such as: abstinence, birth control pills or birth control patches or vaginal ring, diaphragm with spermicide, IUD (intrauterine device), condom with spermicide, progestin implant or injection, surgical sterilization (hysterectomy, bilateral oophorectomy, tubal ligation), or a partner who has had a vasectomy) for the duration of the trial (if female).
- Currently lactating and breast-feeding (if female).
- Evidence of clinically significant immunosuppressive, neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
- Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the volunteer to understand and cooperate with the study protocol.
- Laboratory evidence of liver disease (aspartate aminotransferase greater than 1.25 times the upper limit of normal of the testing laboratory).
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- Laboratory evidence of renal disease (serum creatinine greater than the upper limit of normal of the testing laboratory).
- Laboratory evidence of hematologic disease (absolute neutrophil count <1,500/cubic mm; hemoglobin < 0.9 times the lower limit of normal of the testing laboratory, by sex; or platelet count <140,000/cubic mm).
- 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, or while this study is ongoing.
- 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 (emergency room visit or hospitalization within the last 6 months).
- Serologic evidence of infection with HIV-1, HBV, or HCV.
- Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study or while the study is ongoing.
- Receipt of a live vaccine within past 4 weeks or a killed vaccine within past 2 weeks prior to entry into the study.
- History of surgical splenectomy.
- Receipt of blood products within the past 6 months.
- Previous receipt of an investigational malaria vaccine.
- Receipt of antimalarial prophylaxis during the past 12 months.
- Prior malaria infection.
- Travel to a malaria-endemic country during the past 12 months or planned travel to a malaria-endemic country during the course of the study.
- History of a known allergy to nickel.
- Pre-existing autoimmune or antibody mediated diseases including but not limited to: systemic lupus erythematosis, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia; or laboratory evidence of possible autoimmune disease determined by a positive anti-dsDNA titer, positive rheumatoid factor, proteinuria and/or a positive ANA.
- Chloroquine and related compounds within 12 weeks of study entry.
Trial locations and contacts
1 site in 1 country.
About this study
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
The purpose of this study is to test an experimental malaria vaccine in about 75 healthy adults, 18-45 years of age. The study will also test an experimental adjuvant which is a material added to a vaccine to help the body make more defense cells. The body's immune response (response to foreign substances) and the safety of the vaccine will be tested. All subjects will receive 3 doses of vaccine on days 0, 28, and 56 and doses may increase during the study. Participation in the study is expected to be up to 323 days and includes 16 visits. Study procedures include medical history, physical exams, urine and blood testing.
Read the detailed description
This phase I, dose escalating study will evaluate the safety and immunogenicity of the experimental malaria vaccine AMA1-C1/Alhydrogel®, and the ability of the TLR-9 agonist CPG 7909 oligodeoxynucleotide (ODN) to augment antibody responses to the vaccine and alter the Th1/Th2 bias. The vaccine preparations to be studied contain an equal mixture of AMA1 from two different clones of Plasmodium falciparum (FVO and 3D7). Subjects will be randomly assigned to receive Alydrogel® formulated vaccine with or without CPG 7909 in a point of use formulation. The study will be conducted at the University of Rochester Vaccine and Treatment Evaluation Unit. Subjects for this study will be healthy adults between the ages of 18 and 45 years with no history of malaria or of recent travel to malaria-endemic areas. Subjects will be enrolled in three consecutive dose-escalation cohorts with review by a Safety Monitoring Committee between cohorts. Subjects will receive 3 vaccinations with the AMA1-C1/Alhydrogel® vaccine formulated in Alhydrogel® with or without CPG 7909 adjuvant over 2 months (0, 1, 2 months) by intramuscular (IM) injection. Subjects will have multiple blood samples obtained over the next 6 months. The primary objective of the study is to assess the safety, reactogenicity of the AMA1-C1/Alhydrogel® + CPG 7909 vaccine. The secondary objectives of the study include the following: to demonstrate that the addition of CPG 7909 improves the immune responses to AMA1-FVO and AMA1-3D7, as compared to AMA1-C1/Alhydrogel® at day 70 (14 days after 3rd vaccination; to determine the dose of AMA1-C1/Alhydrogel® + CPG 7909 that generates the highest serum antibody levels of AMA-FVO and AMA1-3D7 at day 70; to assess and compare the duration of antibody responses to AMA1-FVO and AMA1-3D7 proteins by enzyme-linked immunosorbent assay (ELISA) over an 8 month period (6 months after 3rd vaccination); and to perform exploratory studies of B and T cell populations both before and after vaccination. The safety trial endpoints include the frequency and severity of local and systemic adverse events after each dose reported on the subject diary card (solicited adverse events) or reported by subjects spontaneously (unsolicited adverse events) and the presence of abnormal clinical laboratory tests after immunization in each group. The immunogenicity endpoints include the frequency and titer of vaccine induced neutralizing and binding antibody, and the presence and quantity of antigen-specific B cells and CD4 and CD8 T cells producing specified cytokines following vaccination.
- Conditions
- Plasmodium Falciparum Malaria
- Being tested
- AMA1-C1/Alhydrogel®, CPG 7909 Oligodeoxynucleotide (VaxImmune®)
- Keywords
- asexual blood stage vaccine, Plasmodium falciparum malaria
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMA1-C1/Alhydrogel®Biological
AMA1-C1/Alhydrogel malaria vaccine, cloudy suspension, 0.5 mL dose containing up to equivalent of 377 mcg of aluminum as Alhydrogel® (800 mcg of aluminum hydroxide gel per dose) onto which 20 mcg or 80 mcg of recombinant AMA1-C1 is bound. Dosages: 20 mcg and 80 mcg administered via the deltoid muscle by IM injection
CPG 7909 Oligodeoxynucleotide (VaxImmune®)Biological
CPG 7909 is an investigational agent and is supplied in sterile vials at 10mg/mL in phosphate buffered saline for intramuscular administration. Dosage 500 mcg.
| Study group | Role | What they receive |
|---|---|---|
| B | Experimental | 80 mcg AMA1-C1/Alhydrogel® with 368 mcg Aluminum and 500 mg CPG 7909. Receives: Biological: AMA1-C1/Alhydrogel®; Biological: CPG 7909 Oligodeoxynucleotide (VaxImmune®) |
| C | Experimental | 80 mcg AMA1-C1/Alhydrogel® with 368 mcg Aluminum alone. Receives: Biological: AMA1-C1/Alhydrogel® |
| A | Experimental | 20 mcg AMA1-C1/Alhydrogel® with 377 mcg Aluminum and 500 mg CPG 7909. Receives: Biological: AMA1-C1/Alhydrogel®; Biological: CPG 7909 Oligodeoxynucleotide (VaxImmune®) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cellular immune response to vaccination.
Measured: Anti-AMA1 antibody will be measured by ELISA on Days 0, 14, 28, 42, 56, 70, 84, 140, and 236.
Serum antibody response to vaccination.
Measured: Day 70.
Safety: frequency of vaccine-associated adverse events, as classified by severity through active and passive surveillance.
Measured: Duration of study.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2006 (estimated)
- Study startMay 2005
- Primary completionJan 2007
- Study completionJan 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Plasmodium Falciparum MalariaStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00344539
- Sponsor's protocol ID
- 04-075
- Status last verified
- Mar 2013
- First submitted
- 22 Jun 2006
- Last updated
- 3 Jun 2013
- Results posted
- No
Publications
Mullen GE, Ellis RD, Miura K, Malkin E, Nolan C, Hay M, Fay MP, Saul A, Zhu D, Rausch K, Moretz S, Zhou H, Long CA, Miller LH, Treanor J. Phase 1 trial of AMA1-C1/Alhydrogel plus CPG 7909: an asexual blood-stage vaccine for Plasmodium falciparum malaria. PLoS One. 2008 Aug 13;3(8):e2940. doi: 10.1371/journal.pone.0002940.
PubMed 18698359
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00344539
- Acronym / sponsor ID
- 04-075
- Conditions
- Plasmodium Falciparum Malaria
- Keywords
- asexual blood stage vaccine, Plasmodium falciparum malaria
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- May 2005
- Primary completion
- Jan 2007 (actual)
- Study completion
- Jan 2007 (actual)
- First posted
- 26 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to test an experimental malaria vaccine in about 75 healthy adults, 18-45 years of age. The study will also test an experimental adjuvant which is a material added to a vaccine to help the body make more defense cells. The body's immune response (response to foreign substances) and the safety of the vaccine will be tested. All subjects will receive 3 doses of vaccine on days 0, 28, and 56 and doses may increase during the study. Participation in the study is expected to be up to 323 days and includes 16 visits. Study procedures include medical history, physical exams, urine and blood testing.
Detailed description
This phase I, dose escalating study will evaluate the safety and immunogenicity of the experimental malaria vaccine AMA1-C1/Alhydrogel®, and the ability of the TLR-9 agonist CPG 7909 oligodeoxynucleotide (ODN) to augment antibody responses to the vaccine and alter the Th1/Th2 bias. The vaccine preparations to be studied contain an equal mixture of AMA1 from two different clones of Plasmodium falciparum (FVO and 3D7). Subjects will be randomly assigned to receive Alydrogel® formulated vaccine with or without CPG 7909 in a point of use formulation. The study will be conducted at the University of Rochester Vaccine and Treatment Evaluation Unit. Subjects for this study will be healthy adults between the ages of 18 and 45 years with no history of malaria or of recent travel to malaria-endemic areas. Subjects will be enrolled in three consecutive dose-escalation cohorts with review by a Safety Monitoring Committee between cohorts. Subjects will receive 3 vaccinations with the AMA1-C1/Alhydrogel® vaccine formulated in Alhydrogel® with or without CPG 7909 adjuvant over 2 months (0, 1, 2 months) by intramuscular (IM) injection. Subjects will have multiple blood samples obtained over the next 6 months. The primary objective of the study is to assess the safety, reactogenicity of the AMA1-C1/Alhydrogel® + CPG 7909 vaccine. The secondary objectives of the study include the following: to demonstrate that the addition of CPG 7909 improves the immune responses to AMA1-FVO and AMA1-3D7, as compared to AMA1-C1/Alhydrogel® at day 70 (14 days after 3rd vaccination; to determine the dose of AMA1-C1/Alhydrogel® + CPG 7909 that generates the highest serum antibody levels of AMA-FVO and AMA1-3D7 at day 70; to assess and compare the duration of antibody responses to AMA1-FVO and AMA1-3D7 proteins by enzyme-linked immunosorbent assay (ELISA) over an 8 month period (6 months after 3rd vaccination); and to perform exploratory studies of B and T cell populations both before and after vaccination. The safety trial endpoints include the frequency and severity of local and systemic adverse events after each dose reported on the subject diary card (solicited adverse events) or reported by subjects spontaneously (unsolicited adverse events) and the presence of abnormal clinical laboratory tests after immunization in each group. The immunogenicity endpoints include the frequency and titer of vaccine induced neutralizing and binding antibody, and the presence and quantity of antigen-specific B cells and CD4 and CD8 T cells producing specified cytokines following vaccination.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| B | Experimental | Biological: AMA1-C1/Alhydrogel®, Biological: CPG 7909 Oligodeoxynucleotide (VaxImmune®)80 mcg AMA1-C1/Alhydrogel® with 368 mcg Aluminum and 500 mg CPG 7909. |
| C | Experimental | Biological: AMA1-C1/Alhydrogel®80 mcg AMA1-C1/Alhydrogel® with 368 mcg Aluminum alone. |
| A | Experimental | Biological: AMA1-C1/Alhydrogel®, Biological: CPG 7909 Oligodeoxynucleotide (VaxImmune®)20 mcg AMA1-C1/Alhydrogel® with 377 mcg Aluminum and 500 mg CPG 7909. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Age between 18 and 45 years, inclusive.
- Good general health as a result of review of medical history and/or clinical tests.
- Available for the duration of the trial (34 weeks).
- Willingness to participate in the study as evidenced by signing the informed consent document.
Key exclusion criteria (25 listed)
- Pregnancy as determined by a positive urine Beta-hCG (if female) at any point during the study.
- Participant unwilling to use highly effective contraception methods (such as: abstinence, birth control pills or birth control patches or vaginal ring, diaphragm with spermicide, IUD (intrauterine device), condom with spermicide, progestin implant or injection, surgical sterilization (hysterectomy, bilateral oophorectomy, tubal ligation), or a partner who has had a vasectomy) for the duration of the trial (if female).
- Currently lactating and breast-feeding (if female).
- Evidence of clinically significant immunosuppressive, neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
- Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the volunteer to understand and cooperate with the study protocol.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMA1-C1/Alhydrogel®AMA1-C1/Alhydrogel malaria vaccine, cloudy suspension, 0.5 mL dose containing up to equivalent of 377 mcg of aluminum as Alhydrogel® (800 mcg of aluminum hydroxide gel per dose) onto which 20 mcg or 80 mcg of recombinant AMA1-C1 is bound. Dosages: 20 mcg and 80 mcg administered via the deltoid muscle by IM injection | Biological | A, B, C |
| CPG 7909 Oligodeoxynucleotide (VaxImmune®)CPG 7909 is an investigational agent and is supplied in sterile vials at 10mg/mL in phosphate buffered saline for intramuscular administration. Dosage 500 mcg. | Biological | A, B |
Primary outcome
Cellular immune response to vaccination.
Time frame: Anti-AMA1 antibody will be measured by ELISA on Days 0, 14, 28, 42, 56, 70, 84, 140, and 236.
Serum antibody response to vaccination.
Time frame: Day 70.
Safety: frequency of vaccine-associated adverse events, as classified by severity through active and passive surveillance.
Time frame: Duration of study.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2013.
- Results publication: PubMed 18698359Mullen GE, Ellis RD, Miura K, Malkin E, Nolan C, Hay M, Fay MP, Saul A, Zhu D, Rausch K, Moretz S, Zhou H, Long CA, Miller LH, Treanor J. Phase 1 trial of AMA1-C1/Alhydrogel plus CPG 7909: an asexual blood-stage vaccine for Plasmodium falciparum malaria. PLoS One. 2008 Aug 13;3(8):e2940. doi: 10.1371/journal.pone.0002940.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMA1-C1/Alhydrogel® and CPG 7909 Oligodeoxynucleotide (VaxImmune®) in people with Plasmodium Falciparum Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Jun 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cellular immune response to vaccination. (time frame: Anti-AMA1 antibody will be measured by ELISA on Days 0, 14, 28, 42, 56, 70, 84, 140, and 236.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00344539, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2013.