MalariaPhase 1/2NCT01024686
Phase 1/2a Trial of Pf GAP p52-/p36- Sporozoite Malaria Vaccine
A Phase 1/2 study testing p52-/p36- GAP Vaccine and p52-p36- GAP Vaccine in people with Malaria, run by Seattle Children's Hospital at 1 site in United States.
Trial summary
The purpose of this study is to assess safety and tolerability of escalating doses of a genetically attenuated parasite malaria vaccine (p52-/p36- GAP vaccine) in healthy malaria-naive adults. The study will also assess preliminary efficacy of p52-/p36- GAP vaccine following primary experimental challenge with P. 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?
- p52-/p36- GAP Vaccine and p52-p36- GAP Vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2010to Jun 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- A male or non-pregnant, non-lactating female 18 to 50 years of age (inclusive) at the time of enrollment
- Free of significant health problems as established by medical history, laboratory assessment and clinical examination before entering into the study
- Volunteers must have low cardiac risk factors according to the NHANES I criteria and a non-significant electrocardiogram (EKG) as determined by a expert consultant cardiologist
- Available to participate for duration of study
- Reproductive status: a female participant must:
- not be of reproductive potential: i.e. be surgically, medically or physiologically sterile, or
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- if engages in sexual activity that could lead to pregnancy:
- agrees to consistently use contraception until 2 months after the last protocol visit. Contraception is defined as using 1 of the following methods:
- condoms (male or female) with or without a spermicide
- diaphragm or cervical cap with spermicide
- intrauterine device (IUD)
- hormonal contraception
- If the volunteer indicates he/she is active duty military (on the DCT sign-in page and intake form), approval from their supervisor through the Division Director using the Statement of Supervisor's Approval Form must be signed and on file prior to receipt of any test product
- Written informed consent must be obtained from the subject before screening procedures
- Prior to entry into this study, subjects must score at least 80% correct on a 10- question multiple-choice quiz that assesses their understanding of this study.
Who cannot join
- Prior receipt of any investigational malaria vaccine
- Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period
- Administration of any vaccine within 30 days of first study vaccination Any past history of malaria
- Planned travel to malarious areas during the study period
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
- A family history of congenital or hereditary immunodeficiency
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- Moderate or high 5-year cardiovascular risk as determined by NHANES 1 model
- An abnormal 12-lead electrocardiogram (EKG) suggestive of cardiac disease as determined by a clinician
- Seropositive for HIV, Hepatitis C virus (antibodies to HCV) and/or HBsAg
- Hepatomegaly, right upper quadrant abdominal pain or tenderness
- History of splenectomy
- Chronic or active neurologic disease including seizure disorder and chronic migraine headaches
- History of psoriasis and porphyria
- Acute or chronic, clinically significant pulmonary, cardiovascular, ocular, hematologic, hepatic or renal functional abnormality, as determined by physical examination or abnormal baseline laboratory screening tests and medical history review
- Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of vaccination. For corticosteroids, this is defined as prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed.
- Administration of immunoglobulins and/or any blood products within the three months preceding the first dose of study vaccine or planned administration during the study period
- Current chronic use of medications known to cause drug reactions with chloroquine and/or atovaquone/proguanil such as cimetidine and metoclopramide.
- Current chronic use or use within one month prior to enrollment of antibiotics with anti-malarial effects such as tetracyclines for acne, sulfa drugs for recurrent urinary tract infections, etc.
- Pregnant or lactating female
- Female who is willing or intends to become pregnant during the study and for two (2) months after study completion
- Any history of allergic reaction or anaphylaxis to previous vaccination
- History of severe reactions to mosquito bites.
- Inability to make follow-up visits or complete diary cards
- Suspected or known current alcohol abuse/drug abuse as obtained by history and physical examination
- Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Walter Reed Army Institute of Research
Silver Spring, Maryland, 20910
About this study
Official title: Phase 1/2a Trial to Assess the Safety, Immunogenicity and Efficacy of Genetically-attenuated Plasmodium Falciparum Parasites p52-/p36- (GAP) Vaccine, Administered by Bite of Infected Anopheles Mosquito to Malaria-naïve Adults Living in the United States.
The purpose of this study is to assess safety and tolerability of escalating doses of a genetically attenuated parasite malaria vaccine (p52-/p36- GAP vaccine) in healthy malaria-naive adults. The study will also assess preliminary efficacy of p52-/p36- GAP vaccine following primary experimental challenge with P. falciparum sporozoites. Lastly, the study will assess immunogenicity of p52-/p36- GAP in malaria-naïve healthy adults and preliminary efficacy of p52-/p36- GAP vaccine following primary experimental re-challenge with P. falciparum sporozoites.
- Conditions
- Malaria
- Being tested
- p52-/p36- GAP Vaccine, p52-p36- GAP Vaccine
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
p52-/p36- GAP VaccineBiological
Administered by five bites from GAP-infected Anopheles mosquito
p52-p36- GAP VaccineBiological
Administered by 200 bites from GAP-infected Anopeles mosquito
p52-/p36- GAP VaccineBiological
Five doses separated by 4-weeks, each administered by 200 bites from GAP-infected Anopheles mosquito
| Study group | Role | What they receive |
|---|---|---|
| p52-p36- GAP Vaccine | Experimental | p52-/p56- GAP Vaccine: Administered by five bites from GAP-infected Anopheles mosquito.
p52-/p56- GAP Vaccine: Administered by 200 bites from GAP-infected Anopheles mosquito.
Challenge: Administered by five bites from Anopheles mosquitoes infected with wild type NF54 strain Plasmodium falciparum. Receives: Biological: p52-/p36- GAP Vaccine; Biological: p52-p36- GAP Vaccine |
| Infectivity Control | No intervention | Active Control: Administered by five bites from Anopheles mosquitoes infected with wild type NF54 strain Plasmodium falciparum |
| p52-p36- GAP Vaccine + Infectivity Challenge | Experimental | p52-/p36- GAP Vaccine: Five doses separated by 4-weeks, each administered by 200 bites from GAP-infected Anopheles mosquito.
Challenge: Administered by five bites from Anopheles mosquitoes infected with wild type NF54 strain Plasmodium falciparum. Receives: Biological: p52-/p36- GAP Vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of Solicited Adverse Events (AE)
Measured: From administration of study vaccine through 7 days (± 1 days) post dosing
Occurrence of Unsolicited AEs
Measured: From administration of study vaccine through 28 days (± 4 days) post dosing
Occurrence of Laboratory Adverse Events (AE)
Volunteers with any laboratory abnormality.
Measured: From administration of study vaccine through 7 days (± 1 days) post dosing
Detection of Breakthrough Peripheral Parasitemia by Thick Blood Film
Measured: From 7 days after administration of vaccine through 28 days (+ 4 days) post-dosing
Occurrence of Serious Adverse Events (SAE)
Measured: baseline through 28 days
Secondary outcomes (3)
Development of Parasitemia and Time to Parasitemia After Primary Malaria Challenge Following Administration of GAP
Measured: From administration of study vaccine through the duration of the trial
Development of Parasitemia and Time to Parasitemia After Re-challenge Following Administration of GAP
Measured: From administration of study vaccine through the duration of the trial
P. Falciparum Specific Cell-mediated Immune Responses
Measured: From administration of study vaccine through the duration of the trial
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Dec 2009 (estimated)
- Study startMar 2010
- Primary completionJun 2011
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by Seattle Children's HospitalThe 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 1/2
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seattle Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michele Spring, M.D., Principal investigator, Walter Reed Army Institute of Research (WRAIR)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01024686
- Sponsor's protocol ID
- WR 1584
- Status last verified
- Jun 2019
- First submitted
- 1 Dec 2009
- Last updated
- 28 Oct 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Spring M, Murphy J, Nielsen R, Dowler M, Bennett JW, Zarling S, Williams J, de la Vega P, Ware L, Komisar J, Polhemus M, Richie TL, Epstein J, Tamminga C, Chuang I, Richie N, O'Neil M, Heppner DG, Healer J, O'Neill M, Smithers H, Finney OC, Mikolajczak SA, Wang R, Cowman A, Ockenhouse C, Krzych U, Kappe SH. First-in-human evaluation of genetically attenuated Plasmodium falciparum sporozoites administered by bite of Anopheles mosquitoes to adult volunteers. Vaccine. 2013 Oct 9;31(43):4975-83. doi: 10.1016/j.vaccine.2013.08.007. Epub 2013 Sep 8.
PubMed 24029408
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2a Trial to Assess the Safety, Immunogenicity and Efficacy of Genetically-attenuated Plasmodium Falciparum Parasites p52-/p36- (GAP) Vaccine, Administered by Bite of Infected Anopheles Mosquito to Malaria-naïve Adults Living in the United States.
- ClinicalTrials.gov ID
- NCT01024686
- Acronym / sponsor ID
- WR 1584
- Conditions
- Malaria
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Seattle Children's HospitalUniversity, hospital or other
- Study start
- Mar 2010
- Primary completion
- Jun 2011 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 3 Dec 2009 (estimated)
- Results
- Posted 28 Oct 2019
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 assess safety and tolerability of escalating doses of a genetically attenuated parasite malaria vaccine (p52-/p36- GAP vaccine) in healthy malaria-naive adults. The study will also assess preliminary efficacy of p52-/p36- GAP vaccine following primary experimental challenge with P. falciparum sporozoites. Lastly, the study will assess immunogenicity of p52-/p36- GAP in malaria-naïve healthy adults and preliminary efficacy of p52-/p36- GAP vaccine following primary experimental re-challenge with P. falciparum sporozoites.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| p52-p36- GAP Vaccine | Experimental | Biological: p52-/p36- GAP Vaccine, Biological: p52-p36- GAP Vaccinep52-/p56- GAP Vaccine: Administered by five bites from GAP-infected Anopheles mosquito. p52-/p56- GAP Vaccine: Administered by 200 bites from GAP-infected Anopheles mosquito. Challenge: Administered by five bites from Anopheles mosquitoes infected with wild type NF54 strain Plasmodium falciparum. |
| Infectivity Control | No intervention | –Active Control: Administered by five bites from Anopheles mosquitoes infected with wild type NF54 strain Plasmodium falciparum |
| p52-p36- GAP Vaccine + Infectivity Challenge | Experimental | Biological: p52-/p36- GAP Vaccinep52-/p36- GAP Vaccine: Five doses separated by 4-weeks, each administered by 200 bites from GAP-infected Anopheles mosquito. Challenge: Administered by five bites from Anopheles mosquitoes infected with wild type NF54 strain Plasmodium falciparum. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (15 listed)
- A male or non-pregnant, non-lactating female 18 to 50 years of age (inclusive) at the time of enrollment
- Free of significant health problems as established by medical history, laboratory assessment and clinical examination before entering into the study
- Volunteers must have low cardiac risk factors according to the NHANES I criteria and a non-significant electrocardiogram (EKG) as determined by a expert consultant cardiologist
- Available to participate for duration of study
- Reproductive status: a female participant must:
Key exclusion criteria (25 listed)
- Prior receipt of any investigational malaria vaccine
- Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period
- Administration of any vaccine within 30 days of first study vaccination Any past history of malaria
- Planned travel to malarious areas during the study period
- Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
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 |
|---|---|---|
| p52-/p36- GAP VaccineAdministered by five bites from GAP-infected Anopheles mosquito | Biological | p52-p36- GAP Vaccine |
| p52-p36- GAP VaccineAdministered by 200 bites from GAP-infected Anopeles mosquito | Biological | p52-p36- GAP Vaccine |
| p52-/p36- GAP VaccineFive doses separated by 4-weeks, each administered by 200 bites from GAP-infected Anopheles mosquito | Biological | p52-p36- GAP Vaccine + Infectivity Challenge |
Primary outcome
Occurrence of Solicited Adverse Events (AE)
Time frame: From administration of study vaccine through 7 days (± 1 days) post dosing
Occurrence of Unsolicited AEs
Time frame: From administration of study vaccine through 28 days (± 4 days) post dosing
Occurrence of Laboratory Adverse Events (AE)
Time frame: From administration of study vaccine through 7 days (± 1 days) post dosing
Volunteers with any laboratory abnormality.
Detection of Breakthrough Peripheral Parasitemia by Thick Blood Film
Time frame: From 7 days after administration of vaccine through 28 days (+ 4 days) post-dosing
Occurrence of Serious Adverse Events (SAE)
Time frame: baseline through 28 days
3 secondary outcomes
Development of Parasitemia and Time to Parasitemia After Primary Malaria Challenge Following Administration of GAP
Time frame: From administration of study vaccine through the duration of the trial
Development of Parasitemia and Time to Parasitemia After Re-challenge Following Administration of GAP
Time frame: From administration of study vaccine through the duration of the trial
P. Falciparum Specific Cell-mediated Immune Responses
Time frame: From administration of study vaccine through the duration of the trial
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24029408Spring M, Murphy J, Nielsen R, Dowler M, Bennett JW, Zarling S, Williams J, de la Vega P, Ware L, Komisar J, Polhemus M, Richie TL, Epstein J, Tamminga C, Chuang I, Richie N, O'Neil M, Heppner DG, Healer J, O'Neill M, Smithers H, Finney OC, Mikolajczak SA, Wang R, Cowman A, Ockenhouse C, Krzych U, Kappe SH. First-in-human evaluation of genetically attenuated Plasmodium falciparum sporozoites administered by bite of Anopheles mosquitoes to adult volunteers. Vaccine. 2013 Oct 9;31(43):4975-83. doi: 10.1016/j.vaccine.2013.08.007. Epub 2013 Sep 8.
- First-in-human evaluation of genetically attenuated Plasmodium falciparum sporozoites administered by bite of Anopheles mosquitoes to adult volunteers.Link provided by the sponsor.
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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.
Michele Spring, M.D. principal investigator
Walter Reed Army Institute of Research (WRAIR)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing p52-/p36- GAP Vaccine and p52-p36- GAP Vaccine in people with Malaria, run by Seattle Children's Hospital 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 15 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: stopped early, as of the sponsor's last update on 28 Oct 2019. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Occurrence of Solicited Adverse Events (AE) (time frame: From administration of study vaccine through 7 days (± 1 days) post dosing). The study lists 5 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 NCT01024686, 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 28 Oct 2019.