Yellow FeverPhase 1NCT00995865
Trial of Yellow Fever Inactivated Vaccine
A Phase 1 study testing XRX-001 Inactivated yellow fever vaccine in people with Yellow Fever, run by GE Healthcare at 1 site in United States.
Trial summary
The Phase 1 trial is a single-center, randomized, double blind, placebo-controlled, dose-ranging out-patient study designed to provide the first clinical data on the safety, tolerability and immunogenicity of XRX-001 inactivated yellow fever vaccine in 60 healthy male and female volunteers, 18-49 years of age. Read more about this study
- Who is it for?
- Ages 18 to 49 yearsHealthy volunteers can take part
- Conditions the study is for
- Yellow Fever
- What is being tested?
- XRX-001 Inactivated yellow fever vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2010to Oct 2010
- Phase
- Phase 1
- 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 49 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- All aspects of the protocol explained and written informed consent obtained from the subject;
- Aged 18 to 49 years, inclusive;
- In good general health, without significant medical history, physical examination findings, or abnormal laboratory results; and
- Subject must be available for the study duration, including all planned follow-up visits.
- For female subjects of child bearing potential: Negative serum pregnancy tests at Day -7 to -1, and negative urine pregnancy tests prior to vaccination on Days 0, in conjunction with a menstrual and contraceptive history indicating a low probability of pregnancy in the opinion of the physician. Females of childbearing potential will be required to be correctly using an efficacious hormonal method of contraception or intrauterine device for at least 1 month before randomization and during the on-study phase to Day 42. Barrier methods of contraception will not be considered acceptable for study entry. Female subjects of child-bearing potential will acknowledge by signing their informed consent that contraception will be correctly practised during the specified periods and will specify the method used. Female subjects unable to become pregnant must have this documented (e.g. tubal ligation, hysterectomy or postmenopausal [at least one year since last menstrual period]).
Who cannot join
- History of travel to South America or SubSaharan Africa;
- History of active duty military service;
- History of vaccination against yellow fever, tick-borne encephalitis (TBE), or Japanese encephalitis;
- Went to primary (grade) school in Austria, Germany, Japan, South Korea, India, Thailand, Nepal, Vietnam, or Taiwan (where TBE vaccination is practiced)
- History of dengue fever;
- Known or suspected immunodeficiency disorder, including leukemia, lymphoma, generalized malignancy, or treatment with immunosuppressive medications, including corticosteroids, alkylating agents, antimetabolites, or radiation therapy. Low dose steroids (≤ 10 mg prednisone or equivalent, topical or intra-articular/bursal/tendon/epidural injections of corticosteroids) do not constitute a reason for exclusion;
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- History of an autoimmune disorder, including systemic lupus, rheumatoid arthritis, scleroderma, other collagen vascular disease, multiple sclerosis, etc. Psoriasis limited to cutaneous manifestations is not an exclusion criterion;
- Prior history of anaphylaxis to foods, hymenoptera stings, vaccines or drugs;
- Transfusion of blood or treatment with any blood product, including intramuscular or intravenous serum globulin within 3 months of the Screening Visit or anticipated up to Study Day 42;
- Administration of another vaccine within 30 days preceding the screening visit or anticipated up to Day 42 (these subjects may be rescheduled for vaccination at a later date);
- Participation in another clinical trial within 60 days of the screening visit;
- Positive serum or urine pregnancy test prior to vaccination (women of child-bearing potential or lactation or intended pregnancy during study period);
- Abnormalities on laboratory assessment (i.e. meeting the criteria defined for a mild, moderate or severe adverse event in Appendix 1, a1A);
- Seropositive to HIV or HCV or positive for HBsAg;
- Physical examination indicating any clinically significant medical condition;
- Body temperature >38.1°C (100.6°F) or acute illness within 3 days prior to vaccination (subject may be rescheduled);
- Intention to travel out of the area prior to the study visit on Day 42;
- History of excessive alcohol consumption, drug abuse, significant psychiatric illness; and
- Intention to increase normal exercise routine, participate in contact sports or strenuous weight lifting or to initiate vigorous exercise from Screening until after Day 42.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized, Double Blind, Controlled Phase I Trial of the Safety, Tolerability,and Immunogenicity of Graded Doses of XRX-001 Yellow Fever 17D, Inactivated Vaccine, Alum Adsorbed in Healthy Adults.
The Phase 1 trial is a single-center, randomized, double blind, placebo-controlled, dose-ranging out-patient study designed to provide the first clinical data on the safety, tolerability and immunogenicity of XRX-001 inactivated yellow fever vaccine in 60 healthy male and female volunteers, 18-49 years of age. Subjects will receive two inoculations of one of two dose levels of XRX-001 vaccine. A control group will receive placebo.
Safety will be determined by the incidence and severity of adverse events in each treatment group and in the combined cohorts in the double blind treatment period up to 42 days post-vaccination. Subjects will also be followed-up at 3, 6 and 12 months to determine severe adverse events (SAEs) and changes in health status.
Read more
Efficacy will be assessed by neutralizing antibody response to the vaccine. The co-primary immunogenicity endpoints will be the dose-response analysis of seroconversion rates (fourfold or greater increase in neutralizing antibody titer between baseline and Day 42) and of the 50% plaque reduction neutralization test (PRNT50) geometric mean titers (GMT) at Day 42.
Secondary immunogenicity endpoints will include:
- The seroconversion rates and GMT neutralizing antibody titers for all dose groups combined on Days 21 and 42.
- The reverse cumulative distribution curve of antibody titers on Days 21 and 42 for each dose group and for all dose groups combined
- The duration of antibody titers displaying the seroconversion rate and GMT across all time-points to Month 12, by treatment group and for both dose groups combined.
- Conditions
- Yellow Fever
- Being tested
- XRX-001 Inactivated yellow fever vaccine, Placebo
- Keywords
- Prevention of yellow fever virus infection
- Medical subject headings
- Yellow Fever
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XRX-001 Inactivated yellow fever vaccineBiological
Inactivated yellow fever vaccine, alum adsorbed, High dose = 2.3 x 10^8 VE/0.5mL and Mid dose = 2.2 x 10^7 VE/0.5mL
PlaceboBiological
NaCl Injectable 0.9%
| Study group | Role | What they receive |
|---|---|---|
| High dose | Active comparator | Not described Receives: Biological: XRX-001 Inactivated yellow fever vaccine |
| Mid Dose | Active comparator | Not described Receives: Biological: XRX-001 Inactivated yellow fever vaccine |
| Placebo | Placebo comparator | NaCl Injectable 0.9% Receives: Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination.
Subjects were observed for 60 minutes (greater than of equal to 60 minutes and less than of equal to 90 minutes) after vaccine adminstration for any signs or symptoms or local and/or systematic intolerance to the test articles and vital signs were to be checked within the same observation timeframe.
After vaccination, subjects were to complete a memory aid to record daily temperature, symptoms, and concomitant medications from Day-0 to Day-42.
Subjects were to return to the clinic on Days 3, 10, 21, 24, 31, and 42 with a second vaccination given on Day 21.
At each visit, study personnel were to conduct a structured adverse event (AE) interview, and subject were to use their memory aid to assist with the recall of symptoms experiences and daily oral temperatures.
Measured: Measured from 0 up to 21 Days
The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination.
Subjects were observed for 60 minutes (greater than of equal to 60 minutes and less than of equal to 90 minutes) after vaccine adminstration for any signs or symptoms or local and/or systematic intolerance to the test articles and vital signs were to be checked within the same observation timeframe.
After vaccination, subjects were to complete a memory aid to record daily temperature, symptoms, and concomitant medications from Day-0 to Day-42.
Subjects were to return to the clinic on Days 3, 10, 21, 24, 31, and 42 with a second vaccination given on Day 21.
At each visit, study personnel were to conduct a structured adverse event (AE) interview, and subject were to use their memory aid to assist with the recall of symptoms experiences and daily oral temperatures.
Measured: Measured from 22 up to 42 Days.
Secondary outcomes (2)
Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001
Secondary immunogenicity endpoints will use 2 dose levels of XRX-001 inactivated yellow fever vaccine determined by 50% plaque reduction neutralization test (PRNT50). Dose groups were to be compared for neutralizing antibody seroconverison rate, distribution of antibody titers, and geometric mean antibody titers (GMTs) to yellow fever 17D virus. The seroconversion rates and GMT neutralizing antibody titers for each dose group and all dose groups combined; The reverse cumulative distribution curve of antibody titers;
Measured: Days 21 and 42, 12 months
Distribution of Geometric Mean Antibody Titers (GMTs) to Yellow Fever 17D Virus.
Geometric mean antibody titers (GMT) neutralizing antibody titers for each dose groups.
Measured: GMT titers measured at days 21, 31 and 42 for different dose rates.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2009 (estimated)
- Study startJan 2010
- Primary completionMay 2010
- Study completionOct 2010
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 Yellow FeverStudies of the same condition, open and under way.
- More trials run by GE HealthcareThe 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- GE Healthcare
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Amanada Culliton, Study director, GE Healthcare Bio-Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00995865
- Sponsor's protocol ID
- X-100-001
- Status last verified
- Apr 2016
- First submitted
- 8 Oct 2009
- Last updated
- 5 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Monath TP, Fowler E, Johnson CT, Balser J, Morin MJ, Sisti M, Trent DW. An inactivated cell-culture vaccine against yellow fever. N Engl J Med. 2011 Apr 7;364(14):1326-33. doi: 10.1056/NEJMoa1009303.
PubMed 21470010
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double Blind, Controlled Phase I Trial of the Safety, Tolerability,and Immunogenicity of Graded Doses of XRX-001 Yellow Fever 17D, Inactivated Vaccine, Alum Adsorbed in Healthy Adults.
- ClinicalTrials.gov ID
- NCT00995865
- Acronym / sponsor ID
- X-100-001
- Conditions
- Yellow Fever
- Keywords
- Prevention of yellow fever virus infection
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- GE HealthcareIndustry (pharma, biotech, devices)
- Study start
- Jan 2010
- Primary completion
- May 2010 (actual)
- Study completion
- Oct 2010 (actual)
- First posted
- 15 Oct 2009 (estimated)
- Results
- Posted 5 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The Phase 1 trial is a single-center, randomized, double blind, placebo-controlled, dose-ranging out-patient study designed to provide the first clinical data on the safety, tolerability and immunogenicity of XRX-001 inactivated yellow fever vaccine in 60 healthy male and female volunteers, 18-49 years of age. Subjects will receive two inoculations of one of two dose levels of XRX-001 vaccine. A control group will receive placebo.
Safety will be determined by the incidence and severity of adverse events in each treatment group and in the combined cohorts in the double blind treatment period up to 42 days post-vaccination. Subjects will also be followed-up at 3, 6 and 12 months to determine severe adverse events (SAEs) and changes in health status.
Efficacy will be assessed by neutralizing antibody response to the vaccine. The co-primary immunogenicity endpoints will be the dose-response analysis of seroconversion rates (fourfold or greater increase in neutralizing antibody titer between baseline and Day 42) and of the 50% plaque reduction neutralization test (PRNT50) geometric mean titers (GMT) at Day 42.
Secondary immunogenicity endpoints will include:
- The seroconversion rates and GMT neutralizing antibody titers for all dose groups combined on Days 21 and 42.
- The reverse cumulative distribution curve of antibody titers on Days 21 and 42 for each dose group and for all dose groups combined
- The duration of antibody titers displaying the seroconversion rate and GMT across all time-points to Month 12, by treatment group and for both dose groups combined.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| High dose | Active comparator | Biological: XRX-001 Inactivated yellow fever vaccine |
| Mid Dose | Active comparator | Biological: XRX-001 Inactivated yellow fever vaccine |
| Placebo | Placebo comparator | Biological: PlaceboNaCl Injectable 0.9% |
Who may qualify
- Ages
- 18 to 49 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- All aspects of the protocol explained and written informed consent obtained from the subject;
- Aged 18 to 49 years, inclusive;
- In good general health, without significant medical history, physical examination findings, or abnormal laboratory results; and
- Subject must be available for the study duration, including all planned follow-up visits.
- For female subjects of child bearing potential: Negative serum pregnancy tests at Day -7 to -1, and negative urine pregnancy tests prior to vaccination on Days 0, in conjunction with a menstrual and contraceptive history indicating a low probability of pregnancy in the opinion of the physician. Females of childbearing potential will be required to be correctly using an efficacious hormonal method of contraception or intrauterine device for at least 1 month before randomization and during the on-study phase to Day 42. Barrier methods of contraception will not be considered acceptable for study entry. Female subjects of child-bearing potential will acknowledge by signing their informed consent that contraception will be correctly practised during the specified periods and will specify the method used. Female subjects unable to become pregnant must have this documented (e.g. tubal ligation, hysterectomy or postmenopausal [at least one year since last menstrual period]).
Key exclusion criteria (19 listed)
- History of travel to South America or SubSaharan Africa;
- History of active duty military service;
- History of vaccination against yellow fever, tick-borne encephalitis (TBE), or Japanese encephalitis;
- Went to primary (grade) school in Austria, Germany, Japan, South Korea, India, Thailand, Nepal, Vietnam, or Taiwan (where TBE vaccination is practiced)
- History of dengue fever;
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 |
|---|---|---|
| XRX-001 Inactivated yellow fever vaccineInactivated yellow fever vaccine, alum adsorbed, High dose = 2.3 x 10^8 VE/0.5mL and Mid dose = 2.2 x 10^7 VE/0.5mL | Biological | High dose, Mid Dose |
| PlaceboNaCl Injectable 0.9% | Biological | Placebo |
Primary outcome
The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination.
Time frame: Measured from 0 up to 21 Days
Subjects were observed for 60 minutes (greater than of equal to 60 minutes and less than of equal to 90 minutes) after vaccine adminstration for any signs or symptoms or local and/or systematic intolerance to the test articles and vital signs were to be checked within the same observation timeframe. After vaccination, subjects were to complete a memory aid to record daily temperature, symptoms, and concomitant medications from Day-0 to Day-42. Subjects were to return to the clinic on Days 3, 10, 21, 24, 31, and 42 with a second vaccination given on Day 21. At each visit, study personnel were to conduct a structured adverse event (AE) interview, and subject were to use their memory aid to assist with the recall of symptoms experiences and daily oral temperatures.
The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination.
Time frame: Measured from 22 up to 42 Days.
Subjects were observed for 60 minutes (greater than of equal to 60 minutes and less than of equal to 90 minutes) after vaccine adminstration for any signs or symptoms or local and/or systematic intolerance to the test articles and vital signs were to be checked within the same observation timeframe. After vaccination, subjects were to complete a memory aid to record daily temperature, symptoms, and concomitant medications from Day-0 to Day-42. Subjects were to return to the clinic on Days 3, 10, 21, 24, 31, and 42 with a second vaccination given on Day 21. At each visit, study personnel were to conduct a structured adverse event (AE) interview, and subject were to use their memory aid to assist with the recall of symptoms experiences and daily oral temperatures.
2 secondary outcomes
Percentage of Subjects With Seroconversions or Who Are Seropositive Using 2 Dose Levels of XRX-001
Time frame: Days 21 and 42, 12 months
Distribution of Geometric Mean Antibody Titers (GMTs) to Yellow Fever 17D Virus.
Time frame: GMT titers measured at days 21, 31 and 42 for different dose rates.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21470010Monath TP, Fowler E, Johnson CT, Balser J, Morin MJ, Sisti M, Trent DW. An inactivated cell-culture vaccine against yellow fever. N Engl J Med. 2011 Apr 7;364(14):1326-33. doi: 10.1056/NEJMoa1009303.
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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.
Amanada Culliton study director
GE Healthcare Bio-Sciences
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 XRX-001 Inactivated yellow fever vaccine in people with Yellow Fever, run by GE Healthcare 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 5 inclusion and 19 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 5 May 2016. 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 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?
Yes. Results are posted in the registry (first posted 5 May 2016). 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?
The Incidence and Severity of Adverse Events in Each Treatment Group in the Double-blind Treatment Period up to 42 Days Post-vaccination. (time frame: Measured from 0 up to 21 Days). The study lists 2 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 NCT00995865, 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 5 May 2016.