MalariaPhase 1NCT01434381
Initial Study of Malaria Vaccine Pfs25-EPA/Alhydrogel(Registered Trademark)
A Phase 1 study testing Pfs25-EPA/Alhydrogel in people with Malaria, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Background: The malaria vaccine Pfs25-EPA/Alhydrogel may help block malaria parasites from developing in mosquitoes. When a mosquito bites a vaccinated person, the vaccine should prevent parasites from developing in the mosquito. As a result, the mosquito will not spread malaria to the next person it bites. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- Pfs25-EPA/Alhydrogel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2011to Aug 2013
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- All of the following criteria must be fulfilled for a volunteer to participate in this trial:
- Age between 18 and 50 years.
- Good general health as a result of review of medical history and/or clinical testing at the time of screening.
- Available for the duration of the trial.
- Willingness to participate in the study as evidenced by signing the informed consent document.
- If female: subject is willing to use reliable contraception methods for the period of at least 1month (2 months for oral contraceptive pills) prior to first vaccination to 3 months after last vaccination. Reliable methods of birth control include: pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with spermicide; surgical sterilization; vaginal ring; transdermal patch; intrauterine device; abstinence; and post-menopause.
Who cannot join
- A volunteer will be excluded from participating in this trial if any one of the following criteria is fulfilled:
- Pregnancy as determined by a positive urine or serum human choriogonadotropin (Beta-hCG) test at any point during the study (if female).
- Currently is lactating and breast-feeding (if female).
- 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.
- Neutropenia as defined by an absolute neutrophil count < 1500/mm(3).
- Alanine transaminase (ALT) level above the laboratory-defined upper limit of normal.
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- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine, rheumatologic, autoimmune, hematological, or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
- 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.
- History of receiving any investigational product within the past 30 days.
- Receipt of antimalarial prophylaxis during the past 12 months, or planned travel to a destination which would require malaria prophylaxis during the period of participation.
- Prior malaria infection by history.
- Participant 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. This will be defined as:
- Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past 2 years, or that requires the use of oral or parenteral corticosteroids.
- Clinically significant reactive airway disease that does not respond to bronchodilators.
- Positive ELISA and confirmatory Western blot tests for HIV-1.
- Positive ELISA and confirmatory tests for hepatitis C virus (HCV).
- Positive hepatitis B surface antigen (HBsAg) by ELISA.
- 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.
- Known immunodeficiency syndrome.
- Use of chronic (greater than or equal to 14 days) oral or intravenous corticosteroids (excluding topical or nasal) at immunosuppressive doses (i.e. prednisone > 10 mg/ day) or immunosuppressive drugs within 30 days of starting this study.
- 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 a surgical splenectomy.
- Receipt of blood products within the past 6 months.
- Previous receipt of an investigational malaria vaccine.
- Refusal to allow storage of samples for future research.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Open Label Phase 1 Study in Malaria Naive Adults of the Safety and Immunogenicity of Pfs25-EPA/Alhydrogel, a Transmission Blocking Vaccine Against Plasmodium Falciparum
Background:
- The malaria vaccine Pfs25-EPA/Alhydrogel may help block malaria parasites from developing in mosquitoes. When a mosquito bites a vaccinated person, the vaccine should prevent parasites from developing in the mosquito. As a result, the mosquito will not spread malaria to the next person it bites. However, the vaccine will not directly prevent people from getting sick with malaria. Researchers want to test the safety of and response to this vaccine.
Read more
Objectives:
- To test the safety of the malaria vaccine Pfs25-EPA/Alhydrogel.
Eligibility:
- Healthy volunteers between 18 and 50 years of age.
Design:
- Participants will be screened with a medical history, physical exam, and blood tests.
- They will be assigned to a study group to have either two or three doses of the vaccine. Participants will have checkups after each dose of vaccine,
- The additional doses will be given 2 months or 2 and 4 months after the first vaccine.
- Participants will have regular blood tests to check the level of the response to the vaccine.
- They will be followed for up to 1 year after the last vaccine to have any additional tests as needed.
Read the detailed description
A vaccine to interrupt malaria transmission would be a valuable tool for local elimination or eradication of this disease. Pfs25, a surface antigen of ookinetes in the mosquito stage of P. falciparum, is a lead candidate for a malaria transmission blocking vaccine. Recombinant Pfs25 has been conjugated to Pseudomonas aeruginosa ExoProtein A (EPA), and adjuvanted with Alhydrogel(Registered Trademark). This open label, dose escalating Phase 1 study in malaria naive adults, conducted at Johns Hopkins Bloomberg School of Public Health Center for Immunization Research (CIR) in Baltimore, Maryland, will determine initial safety and immunogenicity of the vaccine given on a 2-dose,3-dose, or 4-dose schedule. Thirty (30) volunteers will be enrolled, with 5 receiving the low dose (8 micro g of conjugated Pfs25), 5 receiving the middle dose (16 micro g of conjugated Pfs25), and 20 receiving the high dose (47 micro g of conjugated Pfs25). The high dose group will receive either 2, 3 or 4 doses of vaccine, on a 0, 2, 4 and 10 month vaccination schedule. Volunteers will be followed for 12 months following the last vaccination. Safety outcomes will be local and systemic adverse events (AEs). Immunogenicity outcomes will be antibody responses as measured by ELISA, transmission blocking in a standard membrane feeding assay, and B and T cell responses.
- Conditions
- Malaria
- Being tested
- Pfs25-EPA/Alhydrogel
- Keywords
- Recombinant, Proteins, Antigen, Membrane, Assay, Malaria
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pfs25-EPA/AlhydrogelBiological
| Study group | Role | What they receive |
|---|---|---|
| Pfs25-EPA/Alhydrogel | Experimental | Dose-escalation of Pfs25-EPA/Alhydrogel. Participants will receive 1 of 3 doses of Pfs25-EPA/Alhydrogel- 8 micro g, 16 micro g, or 47 micro g. Receives: Biological: Pfs25-EPA/Alhydrogel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of local and systemic adverse events
Subjects will be monitored for 30 minutes following each immunization. Subjects will return to the clinic on Days 3,7,14 and 28 following each vaccination for clinical assessments, and periodically thereafter until completion
Measured: All adverse events will be recorded though Day 28 after each vaccination. The frequency of systemic and local AEs will be summarized.
Secondary outcomes (1)
To determine the antibody response to the Pfs25 protein vaccines as measured by ELISA and transmission blocking assays, and the effect on antibody responses of a third dose at four months
Measured: ELISA testing will occur on vaccination days, 2 weeks after each vaccination, and periodically until study completion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2011 (estimated)
- Study startAug 2011
- Primary completionAug 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for 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
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Patrick Duffy, MD, Principal investigator, National Institute of Allergy and Infectious Diseases (NIAID)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01434381
- Sponsor's protocol ID
- 11-I-N237
- Other IDs
- 11-I-N237, CIR 276
- Status last verified
- Feb 2014
- First submitted
- 10 Sep 2011
- Last updated
- 11 Feb 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Birkett AJ. PATH Malaria Vaccine Initiative (MVI): perspectives on the status of malaria vaccine development. Hum Vaccin. 2010 Jan;6(1):139-45. doi: 10.4161/hv.6.1.10462. Epub 2010 Jan 29. No abstract available.
PubMed 20009524Cheru L, Wu Y, Diouf A, Moretz SE, Muratova OV, Song G, Fay MP, Miller LH, Long CA, Miura K. The IC(50) of anti-Pfs25 antibody in membrane-feeding assay varies among species. Vaccine. 2010 Jun 17;28(27):4423-9. doi: 10.1016/j.vaccine.2010.04.036. Epub 2010 Apr 29.
PubMed 20434549Coler RN, Baldwin SL, Shaverdian N, Bertholet S, Reed SJ, Raman VS, Lu X, DeVos J, Hancock K, Katz JM, Vedvick TS, Duthie MS, Clegg CH, Van Hoeven N, Reed SG. A synthetic adjuvant to enhance and expand immune responses to influenza vaccines. PLoS One. 2010 Oct 27;5(10):e13677. doi: 10.1371/journal.pone.0013677.
PubMed 21060869
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open Label Phase 1 Study in Malaria Naive Adults of the Safety and Immunogenicity of Pfs25-EPA/Alhydrogel, a Transmission Blocking Vaccine Against Plasmodium Falciparum
- ClinicalTrials.gov ID
- NCT01434381
- Acronym / sponsor ID
- 11-I-N237
- Conditions
- Malaria
- Keywords
- Recombinant, Proteins, Antigen, Membrane, Assay, Malaria
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Aug 2011
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 14 Sep 2011 (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.
Background:
- The malaria vaccine Pfs25-EPA/Alhydrogel may help block malaria parasites from developing in mosquitoes. When a mosquito bites a vaccinated person, the vaccine should prevent parasites from developing in the mosquito. As a result, the mosquito will not spread malaria to the next person it bites. However, the vaccine will not directly prevent people from getting sick with malaria. Researchers want to test the safety of and response to this vaccine.
Objectives:
- To test the safety of the malaria vaccine Pfs25-EPA/Alhydrogel.
Eligibility:
- Healthy volunteers between 18 and 50 years of age.
Design:
- Participants will be screened with a medical history, physical exam, and blood tests.
- They will be assigned to a study group to have either two or three doses of the vaccine. Participants will have checkups after each dose of vaccine,
- The additional doses will be given 2 months or 2 and 4 months after the first vaccine.
- Participants will have regular blood tests to check the level of the response to the vaccine.
- They will be followed for up to 1 year after the last vaccine to have any additional tests as needed.
Detailed description
A vaccine to interrupt malaria transmission would be a valuable tool for local elimination or eradication of this disease. Pfs25, a surface antigen of ookinetes in the mosquito stage of P. falciparum, is a lead candidate for a malaria transmission blocking vaccine. Recombinant Pfs25 has been conjugated to Pseudomonas aeruginosa ExoProtein A (EPA), and adjuvanted with Alhydrogel(Registered Trademark). This open label, dose escalating Phase 1 study in malaria naive adults, conducted at Johns Hopkins Bloomberg School of Public Health Center for Immunization Research (CIR) in Baltimore, Maryland, will determine initial safety and immunogenicity of the vaccine given on a 2-dose,3-dose, or 4-dose schedule. Thirty (30) volunteers will be enrolled, with 5 receiving the low dose (8 micro g of conjugated Pfs25), 5 receiving the middle dose (16 micro g of conjugated Pfs25), and 20 receiving the high dose (47 micro g of conjugated Pfs25). The high dose group will receive either 2, 3 or 4 doses of vaccine, on a 0, 2, 4 and 10 month vaccination schedule. Volunteers will be followed for 12 months following the last vaccination. Safety outcomes will be local and systemic adverse events (AEs). Immunogenicity outcomes will be antibody responses as measured by ELISA, transmission blocking in a standard membrane feeding assay, and B and T cell responses.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pfs25-EPA/Alhydrogel | Experimental | Biological: Pfs25-EPA/AlhydrogelDose-escalation of Pfs25-EPA/Alhydrogel. Participants will receive 1 of 3 doses of Pfs25-EPA/Alhydrogel- 8 micro g, 16 micro g, or 47 micro g. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- All of the following criteria must be fulfilled for a volunteer to participate in this trial:
- Age between 18 and 50 years.
- Good general health as a result of review of medical history and/or clinical testing at the time of screening.
- Available for the duration of the trial.
- Willingness to participate in the study as evidenced by signing the informed consent document.
Key exclusion criteria (28 listed)
- A volunteer will be excluded from participating in this trial if any one of the following criteria is fulfilled:
- Pregnancy as determined by a positive urine or serum human choriogonadotropin (Beta-hCG) test at any point during the study (if female).
- Currently is lactating and breast-feeding (if female).
- 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.
- Neutropenia as defined by an absolute neutrophil count < 1500/mm(3).
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 |
|---|---|---|
| Pfs25-EPA/Alhydrogel | Biological | Pfs25-EPA/Alhydrogel |
Primary outcome
Incidence of local and systemic adverse events
Time frame: All adverse events will be recorded though Day 28 after each vaccination. The frequency of systemic and local AEs will be summarized.
Subjects will be monitored for 30 minutes following each immunization. Subjects will return to the clinic on Days 3,7,14 and 28 following each vaccination for clinical assessments, and periodically thereafter until completion
1 secondary outcome
To determine the antibody response to the Pfs25 protein vaccines as measured by ELISA and transmission blocking assays, and the effect on antibody responses of a third dose at four months
Time frame: ELISA testing will occur on vaccination days, 2 weeks after each vaccination, and periodically until study completion
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 11 Feb 2014.
- Background: PubMed 20009524Birkett AJ. PATH Malaria Vaccine Initiative (MVI): perspectives on the status of malaria vaccine development. Hum Vaccin. 2010 Jan;6(1):139-45. doi: 10.4161/hv.6.1.10462. Epub 2010 Jan 29. No abstract available.
- Background: PubMed 20434549Cheru L, Wu Y, Diouf A, Moretz SE, Muratova OV, Song G, Fay MP, Miller LH, Long CA, Miura K. The IC(50) of anti-Pfs25 antibody in membrane-feeding assay varies among species. Vaccine. 2010 Jun 17;28(27):4423-9. doi: 10.1016/j.vaccine.2010.04.036. Epub 2010 Apr 29.
- Background: PubMed 21060869Coler RN, Baldwin SL, Shaverdian N, Bertholet S, Reed SJ, Raman VS, Lu X, DeVos J, Hancock K, Katz JM, Vedvick TS, Duthie MS, Clegg CH, Van Hoeven N, Reed SG. A synthetic adjuvant to enhance and expand immune responses to influenza vaccines. PLoS One. 2010 Oct 27;5(10):e13677. doi: 10.1371/journal.pone.0013677.
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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.
Patrick Duffy, MD principal investigator
National Institute of Allergy and Infectious Diseases (NIAID)
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 Pfs25-EPA/Alhydrogel in people with 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 6 inclusion and 28 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 11 Feb 2014. 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?
Incidence of local and systemic adverse events (time frame: All adverse events will be recorded though Day 28 after each vaccination. The frequency of systemic and local AEs will be summarized.). 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 NCT01434381, which also lists 3 linked publications.
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 11 Feb 2014.