MalariaPhase 1/2NCT01397227
A Study to Assess the Immunogenicity, Tolerability and Safety of a Malaria Vaccine and Also Its Protective Efficacy in a Malaria Challenge Model
A Phase 1/2 study testing Ad35.CS.01/Ad26.CS.01 low dose (1 x 10^10 vp) and Ad 35.CS.01/Ad 26.CS.01 high dose (5 x 10^10 vp) in people with Malaria, run by Crucell Holland BV at 1 site in United States.
Trial summary
The purpose of this study is to assess the safety, tolerability and immunogenicity of two dose levels (1x10^10 and 5x10^10 virus particles (vp)) of the adenovirus serotype (Ad) Ad35.CS.01/Ad26.CS.01 prime-boost malaria candidate vaccine, followed by an evaluation of the protective efficacy of the higher dose level in… 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?
- Ad35.CS.01/Ad26.CS.01 low dose (1 x 10^10 vp) and Ad 35.CS.01/Ad 26.CS.01 high dose (5 x 10^10 vp)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2011to May 2012
- Phase
- Phase 1/2
- 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
- Healthy male or non-pregnant female subjects aged ≥18 to ≤50 years on Study Day 0.
- Able and willing to participate for the duration of the study, to comply with protocol provisions and to undergo malaria challenge.
- Able and willing to provide written informed consent.
- Free of obvious health-problems as established by medical history, physical examination, laboratory assessment and clinical judgment of the investigator.
- If the participant is biologically female she must:
- Have a negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test performed at screening within 7 days before the 1st vaccine administration, and agree to a urine β-hCG pregnancy test at Study Day 0 and at each subsequent vaccine administration, before the challenge period, and at the end of the challenge period.
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- Agree to consistently use effective contraception from 21 days prior to Study Day 0 for the duration of the study, for sexual activity that could lead to pregnancy.
- Agree to not seek pregnancy through alternative methods such as artificial insemination or in vitro fertilization until after the last scheduled protocol visit.
- Male subjects engaged in sexual activities which could lead to pregnancy must agree to use a reliable barrier contraceptive plus spermicide for the duration of the study.
Who cannot join
- Clinically significant medical condition, physical examination findings, other clinically significant abnormal laboratory results, or past medical history that may have implications for current health status in the opinion of the Investigator. A clinically significant condition or process includes but is not limited to:
- A process that would affect the immune response,
- A process that would require medication that affects the immune response,
- Any contraindication to repeated phlebotomy,
- A condition or process in which signs or symptoms could be confused with reactions to vaccination or malaria challenge and/or infection, including dermatologic abnormalities at the site of sporozoite inoculation/vaccination, or
- Any condition specifically listed among the exclusion criteria below.
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- Clinically significant acute illness, including oral temperature >38.0 °C, or infection within 2 weeks of Study Day 0 that, in the opinion of the Investigator, would interfere with study assessments or cause significant implications for subject safety.
- History of, or known active cardiac disease including: (1) prior myocardial infarction (heart attack); (2) angina pectoris; (3) congestive heart failure; (4) valvular heart disease; (5) cardiomyopathy; (6) pericarditis; (7) stroke or transient ischemic attack; (8) exertional chest pain or shortness of breath; or (9) other heart conditions under the care of a doctor.
- Elevated (moderate or high) risk of coronary heart disease as determined by the NHANES I cardiovascular risk assessment criteria.
- Clinically significant ECG findings, as determined by the study cardiologist.
- History of malignancy, including hematologic and skin cancers (except for a localized basal cell carcinoma).
- History of coagulation defects or bleeding that can not be linked to trauma or surgery.
- History of receiving blood or blood products (such as blood transfusions, platelet transfusion, immunoglobulins, hyperimmune serum) within 6 months prior to Study Day 0.
- History of mental illness as defined by symptoms interfering with social or occupational function or suicidal thoughts / attempts, excluding minor depression resolved or successfully treated at least 3 years prior to Study Day 0.
- Any clinically significant history of known or suspected anaphylaxis or hypersensitivity reaction to vaccinations.
- History of splenectomy.
- Clinically significant screening laboratory abnormalities within 90 days of Study Day 0.
- Positive serology for human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B surface antigen (HBsAg).
- Positive Neutralizing Antibody titers (IC90 >16) against Ad26 and/or Ad35.
- Pregnant or lactating female.
- Chronic (longer than 14 days) administration of immunosuppressants (including oral or inhaled) or other immune-modifying drugs within 6 months prior to Study Day 0, including oral corticosteroids in dosages of ≥0.5 mg/kg/day prednisone or equivalent.
- Blood donation (typical US blood volume donations are 470 mL) or significant blood loss (defined as total cumulative volume >500 mL, including screening blood volumes) within 56 days before first dosing or plasma donation within 7 days prior to Study Day 0.
- Vaccination with a live vaccine within 30 days prior to Study Day 0 or with a non-replicating, inactivated or subunit vaccine within 14 days prior to Study Day 0 or planned vaccination of any type during the study period.
- Prior receipt of a malaria vaccine.
- Any history of malaria diagnosed on positive blood smear.
- Use of antimalarial prophylaxis, or travel to a malaria endemic region within 6 months prior to Study Day 0.
- Any history of residence (>3 months) in area known to have significant transmission of Plasmodium falciparum.
- Planned travel to a malaria endemic region during the study period.
- Prior receipt of a recombinant adenovirus vector vaccine.
- Known hypersensitivity to components of the vaccine or proposed antimalarial medications.
- Employee at the malaria clinical trial center or investigator or relative children or spouse of any investigator.
- Identification of any condition or finding that, in the opinion of the investigator, would interfere with or serve as a contraindication to protocol adherence, assessment of study endpoints or would jeopardize the rights, safety or welfare of the subject participating in the study.
- Smokers with current use of >10 cigarettes/day or >15 pack-years of lifetime cigarette use.
- Known history of hemoglobinopathy.
- Suspected or known alcohol or drug abuse as defined by the American Psychiatric Association in the DSM IV.
- Ocular disease defined as retinopathy or visual field defects.
- Chronic neurological symptoms including seizures or migraine headaches.
- Concurrent participation in other investigational protocols or in receipt of an investigational product within the previous 6 months of Study Day 0 or planned receipt of another investigational product during the course of the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Malaria Clinical Trials Center at Seattle Biomedical Research Institute
Seattle, Washington, 98109
About this study
Official title: A Phase I/IIa, Double-blind, Randomized, Placebo-controlled, Dose-escalation Clinical Study Evaluating Safety, Tolerability and Immunogenicity of Two Dose Levels of Recombinant Adenoviral Serotype Ad35 and Serotype Ad26 Vectors Expressing the Malaria Plasmodium Falciparum Circumsporozoite Antigen Administered as Heterologous Prime-boost Regimen, and Assessing Protective Efficacy of the Higher Dose in a Malaria Challenge Model in Unblinded Conditions
The purpose of this study is to assess the safety, tolerability and immunogenicity of two dose levels (1x10^10 and 5x10^10 virus particles (vp)) of the adenovirus serotype (Ad) Ad35.CS.01/Ad26.CS.01 prime-boost malaria candidate vaccine, followed by an evaluation of the protective efficacy of the higher dose level in an experimental malaria challenge.
The study will be in 3 phases:
- a dose escalation / vaccination phase in which both dose levels will be tested
- a malaria challenge phase in which only subjects receiving the Ad35.CS.01/Ad26.CS.01 5x10^10 vp dose level, together with six infectivity control subjects, will be exposed to experimental challenge with Plasmodium falciparum
- a long term follow up phase in which all subjects who received active vaccine from both dose levels and/or malaria challenge will be included
- Conditions
- Malaria
- Being tested
- Ad35.CS.01/Ad26.CS.01 low dose (1 x 10^10 vp), Ad 35.CS.01/Ad 26.CS.01 high dose (5 x 10^10 vp), Placebo
- Keywords
- Malaria, Plasmodium falciparum, Vaccination, Prophylaxis, Adenovirus
- Medical subject headings
- Malaria, Malaria, Falciparum, Adenoviridae Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ad35.CS.01/Ad26.CS.01 low dose (1 x 10^10 vp)Biological
Prime-boost schedule: Each subject receives two injections of Ad35.CS.01 (on Days 0 and 28) followed by one injection of Ad26.CS.01 (on either Day 55 or 59).
Ad 35.CS.01/Ad 26.CS.01 high dose (5 x 10^10 vp)Biological
Prime-boost schedule: Each subject receives two injections of Ad35.CS.01 (on Days 0 and 28) followed by one injection of Ad26.CS.01 (on either Day 55 or 59).
PlaceboBiological
Each placebo subject receives in total three injections of placebo: Day 0, Day 28, and either Day 55 or 59
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 (Low Dose) | Experimental | Ad35.CS.01/Ad26.CS.01 - 1 x 10^10 vp Receives: Biological: Ad35.CS.01/Ad26.CS.01 low dose (1 x 10^10 vp) |
| Cohort 2 (High Dose) | Experimental | Ad35.CS.01/Ad26.CS.01 - 5 x 10^10 vp Receives: Biological: Ad 35.CS.01/Ad 26.CS.01 high dose (5 x 10^10 vp) |
| Cohort 1 - Placebo | Placebo comparator | Not described Receives: Biological: Placebo |
| Cohort 2 - Placebo | Placebo comparator | Not described Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Solicited local and systemic adverse events (AEs)
Type and frequency of solicited local and systemic AEs to be recorded. Solicited AEs in the challenge period are collected via a reactogenicity checklist during study visits. Solicited AEs in the vaccination period are collected via a Subject Diary.
Measured: For 7 days after each vaccination and at each visit during the challenge period
Unsolicited AEs
Type and frequency of unsolicited AEs to be recorded
Measured: At each visit during the vaccination period
Vital signs
Temperature (oral), pulse, respiratory rate, blood pressure and pulse oximetry will be measured
Measured: Before and after each vaccination during the vaccination period, before and after malaria challenge and at each visit during the challenge period
Changes in laboratory parameters from baseline to end of vaccination phase
Assessment made on the changes in each laboratory parameter from baseline to the end of the vaccination phase at each time point. Parameters measured:
Biochemistry: glucose, potassium, creatinine, γ-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, C-reactive protein and erythrocyte sedimentation rate.
Hematology: hemoglobin, hematocrit, white blood cell count, white blood cell differential, red blood cell count and platelet count.
Urinalysis: leucocytes, blood, protein, ketones and glucose (by dipstick).
Measured: Screening/baseline, 7 days after each vaccination, and Days 101 and 115 of the challenge period
Secondary outcomes (2)
Immunogenicity
- Anti-circumsporozoite antibodies will be assessed by enzyme-linked immunosorbent assay
- T-cell responses against circumsporozoite protein will be assessed by ELISPOT assays and flow cytometry
- Neutralizing antibodies to Ad26, and Ad35 will be assessed by neutralizing antibody assay
Measured: Blood samples drawn at baseline (screening) and Study Days 14, 28, 42, 55/59, 69/73, 86 and 115
Efficacy - patent parasitemia
Development of patent parasitemia diagnosed on peripheral blood smear
Measured: Vaccine recipients are monitored for the development of parasitemia for 28 days post-malaria challenge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2011 (estimated)
- Study startJun 2011
- Primary completionMay 2012
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MalariaStudies of the same condition, open and under way.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Crucell Holland BV
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- The PATH Malaria Vaccine Initiative (MVI), Seattle Children's Hospital
- Responsible party
- Sponsor
- Investigators
- Angela Talley, MD, Principal investigator, Seattle Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01397227
- Sponsor's protocol ID
- MAL-V-A001
- Status last verified
- Sep 2012
- First submitted
- 12 Jul 2011
- Last updated
- 7 Sep 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/IIa, Double-blind, Randomized, Placebo-controlled, Dose-escalation Clinical Study Evaluating Safety, Tolerability and Immunogenicity of Two Dose Levels of Recombinant Adenoviral Serotype Ad35 and Serotype Ad26 Vectors Expressing the Malaria Plasmodium Falciparum Circumsporozoite Antigen Administered as Heterologous Prime-boost Regimen, and Assessing Protective Efficacy of the Higher Dose in a Malaria Challenge Model in Unblinded Conditions
- ClinicalTrials.gov ID
- NCT01397227
- Acronym / sponsor ID
- MAL-V-A001
- Conditions
- Malaria
- Keywords
- Malaria, Plasmodium falciparum, Vaccination, Prophylaxis, Adenovirus
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Crucell Holland BVIndustry (pharma, biotech, devices)
- Collaborators
- The PATH Malaria Vaccine Initiative (MVI), Seattle Children's Hospital
- Study start
- Jun 2011
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 19 Jul 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.
The purpose of this study is to assess the safety, tolerability and immunogenicity of two dose levels (1x10^10 and 5x10^10 virus particles (vp)) of the adenovirus serotype (Ad) Ad35.CS.01/Ad26.CS.01 prime-boost malaria candidate vaccine, followed by an evaluation of the protective efficacy of the higher dose level in an experimental malaria challenge.
The study will be in 3 phases:
- a dose escalation / vaccination phase in which both dose levels will be tested
- a malaria challenge phase in which only subjects receiving the Ad35.CS.01/Ad26.CS.01 5x10^10 vp dose level, together with six infectivity control subjects, will be exposed to experimental challenge with Plasmodium falciparum
- a long term follow up phase in which all subjects who received active vaccine from both dose levels and/or malaria challenge will be included
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 (Low Dose) | Experimental | Biological: Ad35.CS.01/Ad26.CS.01 low dose (1 x 10^10 vp)Ad35.CS.01/Ad26.CS.01 - 1 x 10^10 vp |
| Cohort 2 (High Dose) | Experimental | Biological: Ad 35.CS.01/Ad 26.CS.01 high dose (5 x 10^10 vp)Ad35.CS.01/Ad26.CS.01 - 5 x 10^10 vp |
| Cohort 1 - Placebo | Placebo comparator | Biological: Placebo |
| Cohort 2 - Placebo | Placebo comparator | Biological: Placebo |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Healthy male or non-pregnant female subjects aged ≥18 to ≤50 years on Study Day 0.
- Able and willing to participate for the duration of the study, to comply with protocol provisions and to undergo malaria challenge.
- Able and willing to provide written informed consent.
- Free of obvious health-problems as established by medical history, physical examination, laboratory assessment and clinical judgment of the investigator.
- If the participant is biologically female she must:
Key exclusion criteria (38 listed)
- Clinically significant medical condition, physical examination findings, other clinically significant abnormal laboratory results, or past medical history that may have implications for current health status in the opinion of the Investigator. A clinically significant condition or process includes but is not limited to:
- A process that would affect the immune response,
- A process that would require medication that affects the immune response,
- Any contraindication to repeated phlebotomy,
- A condition or process in which signs or symptoms could be confused with reactions to vaccination or malaria challenge and/or infection, including dermatologic abnormalities at the site of sporozoite inoculation/vaccination, or
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 |
|---|---|---|
| Ad35.CS.01/Ad26.CS.01 low dose (1 x 10^10 vp)Prime-boost schedule: Each subject receives two injections of Ad35.CS.01 (on Days 0 and 28) followed by one injection of Ad26.CS.01 (on either Day 55 or 59). | Biological | Cohort 1 (Low Dose) |
| Ad 35.CS.01/Ad 26.CS.01 high dose (5 x 10^10 vp)Prime-boost schedule: Each subject receives two injections of Ad35.CS.01 (on Days 0 and 28) followed by one injection of Ad26.CS.01 (on either Day 55 or 59). | Biological | Cohort 2 (High Dose) |
| PlaceboEach placebo subject receives in total three injections of placebo: Day 0, Day 28, and either Day 55 or 59 | Biological | Cohort 1 - Placebo, Cohort 2 - Placebo |
Primary outcome
Solicited local and systemic adverse events (AEs)
Time frame: For 7 days after each vaccination and at each visit during the challenge period
Type and frequency of solicited local and systemic AEs to be recorded. Solicited AEs in the challenge period are collected via a reactogenicity checklist during study visits. Solicited AEs in the vaccination period are collected via a Subject Diary.
Unsolicited AEs
Time frame: At each visit during the vaccination period
Type and frequency of unsolicited AEs to be recorded
Vital signs
Time frame: Before and after each vaccination during the vaccination period, before and after malaria challenge and at each visit during the challenge period
Temperature (oral), pulse, respiratory rate, blood pressure and pulse oximetry will be measured
Changes in laboratory parameters from baseline to end of vaccination phase
Time frame: Screening/baseline, 7 days after each vaccination, and Days 101 and 115 of the challenge period
Assessment made on the changes in each laboratory parameter from baseline to the end of the vaccination phase at each time point. Parameters measured: Biochemistry: glucose, potassium, creatinine, γ-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, C-reactive protein and erythrocyte sedimentation rate. Hematology: hemoglobin, hematocrit, white blood cell count, white blood cell differential, red blood cell count and platelet count. Urinalysis: leucocytes, blood, protein, ketones and glucose (by dipstick).
2 secondary outcomes
Immunogenicity
Time frame: Blood samples drawn at baseline (screening) and Study Days 14, 28, 42, 55/59, 69/73, 86 and 115
Efficacy - patent parasitemia
Time frame: Vaccine recipients are monitored for the development of parasitemia for 28 days post-malaria challenge
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 7 Sep 2012.
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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.
Angela Talley, MD principal investigator
Seattle Children's Hospital
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 Ad35.CS.01/Ad26.CS.01 low dose (1 x 10^10 vp) and Ad 35.CS.01/Ad 26.CS.01 high dose (5 x 10^10 vp) in people with Malaria, run by Crucell Holland BV 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 9 inclusion and 38 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 7 Sep 2012. 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. Some participants in this study may receive a placebo. 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?
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?
Solicited local and systemic adverse events (AEs) (time frame: For 7 days after each vaccination and at each visit during the challenge period). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Sep 2012.