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TuberculosisPhase 1NCT02508376

Safety, Tolerability, and Immunogenicity of the Vaccine Candidates ID93 + AP10-602 and ID93 + GLA-SE Administered Intramuscularly in Healthy Adult Subjects

A Phase 1 study testing AP10-602, GLA-SE and ID93 in people with Tuberculosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a phase I randomized, double blind clinical trial designed to evaluate the safety, tolerability and immunogenicity of the ID93 recombinant protein antigen alone or formulated with GLA-SE or AP10-602 adjuvant in 70 healthy adults 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
Tuberculosis
What is being tested?
AP10-602, GLA-SE and ID93
Could I receive a placebo?
No, everyone receives an active treatment
How many people
70 participants
Where
1 siteUnited States
Study dates
22 Oct 2015to 31 Aug 2017
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 49 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 1. Males and nonpregnant females between the ages of 18 and 49 years, inclusive. 2. Women of childbearing potential must agree to practice adequate contraception for the 28-day period before Day 0 through 90 days after the third study injection. A woman is considered of childbearing potential unless surgically sterile (tubal ligation, bilateral oophorectomy, or hysterectomy) or post-menopausal (>/=1 year). Acceptable birth control methods include but are not limited to: abstinence from sexual intercourse with men; monogamous relationship with a vasectomized partner; barrier methods (condoms, diaphragms, spermicides, and intrauterine devices); and licensed hormonal methods. 3. In good health, as judged by the investigator and determined by vital signs, medical history, and a targeted physical examination. Temperature <38°C, heart rate </=100 bpm and >54 bpm, systolic blood pressure </=140 mmHg and >89 mmHg, diastolic blood pressure </=90 mmHg and >/=60 mmHg. NOTE: Athletically trained subjects with a pulse >/=45 may be enrolled at the discretion of the principal investigator or designated licensed clinical investigator. 4. Screening laboratory values must be within site normal limits, though trace urine protein is acceptable. -Blood hemoglobin -White blood cell (WBC) count -Neutrophil count -Platelets -Creatinine -AST -ALT -Bilirubin (total) -Glucose (random, must be less than 140) -Urine dipstick for protein and glucose (negative to trace protein are acceptable) -Negative Quantiferon-TB Gold test -Negative HIV 1/2 antibody, (HBsAg), and Hepatitis C virus (HCV) antibody NOTE: See Appendix D for site normal values. Creatinine values lower than the normal range may be acceptable if the PI or a designated licensed clinician determines that these laboratory findings are not clinically significant. HIV and hepatitis C viral load PCR testing may be performed for individuals suspected of having indeterminate antibody testing. For African American participants, a WBC of >/= 3.5 k/mm^3 is acceptable. 5. Able to understand and comply with planned study procedures and willing to be available for all study-required procedures, visits and calls for the duration of the study. 6. Provide written informed consent before initiation of any study procedures. 7. Willing to abstain from donating whole blood or blood derivatives until 90 days after the final study injection.

Who cannot join

  • 1. History of treatment for active or latent tuberculosis infection or history of positive PPD. 2. History or evidence of active tuberculosis. 3. Has received vaccination or immunotherapy with a BCG product at any time prior to randomization. 4. Shared a residence within the last year prior to randomization with an individual on anti-tuberculosis treatment or with culture or smear positive tuberculosis. 5. Received a tuberculin skin test within 3 months (90 days) prior to the time of randomization through study day 85. 6. Body temperature >/=100.4°F (>/=38°C) or acute illness within 3 days before study injection days (subject may be rescheduled). 7. A positive serum or urine pregnancy test at screening or within 24 hours prior to study injection, women who are planning to become pregnant, or women who are breastfeeding. At screening visit only If female of childbearing potential as defined in Inclusion Criterion #2 from 28 days prior to entering the study until 90 days after the final study injection 8. Immunosuppression as a result of an underlying illness or treatment or use of anticancer chemotherapy or radiation therapy (cytotoxic) within the preceding 36 months. 9. An active neoplastic disease (excluding nonmelanoma skin cancer) or a history of any hematologic malignancy. defined as neoplastic disease or treatment for neoplastic disease within the past 5 years 10. A history of autoimmune disease (systemic lupus, rheumatoid arthritis, scleroderma, polyarteritis, thyroiditis, etc). 11. Used an immunosuppressive or immunomodulatory drug for 2 or more consecutive weeks within 6 months prior to the first study injection (nasal and topical steroids are allowed). such as >0.5 mg/kg/day or >/=20 mg total dose/day of prednisone orally or >800 µg of inhaled beclomethasone 12. A diagnosis of schizophrenia, bipolar disease, or history of hospitalization for a psychiatric condition or previous suicide attempt. 13. A history of treatment for any other psychiatric disorder in the past 3 years that increases the risk to the subject in the opinion of the investigator. 14. A history of receiving immunoglobulin or other blood product within 3 months prior to enrollment through study day 85. 15. Received or plan to receive any live licensed vaccines within 4 weeks or inactivated licensed vaccines within 2 weeks of any study injection. 16. An acute or chronic medical condition that would render study injections unsafe or would interfere with the evaluation of responses or is not generally seen in healthy, normal subjects. in the opinion of the investigator NOTE: This includes, but is not limited to, known cardiac disease, pulmonary disease, liver disease, renal disease, unstable or progressive neurological disorders, diabetes mellitus, and transplant recipients. 17. History of anaphylaxis or severe allergic reaction to vaccines or history of allergic reaction to eggs, kanamycin-related antibiotics or other components in the antigen and adjuvant formulations. 18. Receipt of an experimental agent within 1 month before study injections in this study or expectation to receive an experimental agent during the 15-month study period. vaccine, drug, biologic, device, blood product, or medication 19. Any condition that would place the subject at an unacceptable injury risk, render him/her unable to meet the requirements of the protocol, or that may interfere with successful study completion. in the opinion of the investigator 20. A history of alcohol or drug abuse during the previous 1 year or chronic marijuana abuse or any other illicit drug use. for example, daily excessive alcohol use or frequ ent binge drinking as determined by the investigator 21. Presence of tattoos that would preclude evaluation of the injection site.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Iowa - Vaccine Research and Education Unit

    Iowa City, Iowa, 52242-2600

Other trials in United States

About this study

Official title: A Phase 1, Randomized, Double Blind Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of the Vaccine Candidates ID93 + AP10-602 and ID93 + GLA-SE Administered Intramuscularly in Healthy Adult Subjects

This is a phase I randomized, double blind clinical trial designed to evaluate the safety, tolerability and immunogenicity of the ID93 recombinant protein antigen alone or formulated with GLA-SE or AP10-602 adjuvant in 70 healthy adults 18-49 years of age. Subjects will receive a total of 3 doses administered intramuscularly on Days 1, 29 and 57. Subjects will be monitored for approximately 422 days (365 days following the third study injection), including safety laboratory analyses done just prior to and 7 days following each study injection. Blood samples will be obtained for immunological assays (Luminex, intracellular cytokine staining at Days 1 and 71, and antibody analysis at Days 1 and 85). The primary objective is to evaluate the safety and tolerability of 10 µg ID93 + 5 or 10 µg AP10-602 compared to 10 µg ID93 + 5 µg GLA-SE and 10 µg ID93 alone following three consecutive intramuscular injections administered on Days 1, 29 and 57.

Read the detailed description

TB causes significant morbidity and mortality throughout the world. Strains of Mtb are becoming increasingly resistant to antimycobacterial drugs and therapy is often associated with poor compliance, which increases the likelihood of antimicrobial resistance. The current licensed BCG vaccine does not prevent reactivation or reinfection in adults so there is a great need for a more effective vaccine. ID93 is a recombinant antigen that, when mixed with the adjuvants GLA-SE and AP10-602, shows great promise in eliciting what is thought to be an important Th1 T cell response and limits the bacterial burden in Mtb challenged animals. This study is a phase I randomized, double blind clinical trial designed to evaluate the safety, tolerability and immunogenicity of the ID93 recombinant protein antigen alone or formulated with GLA-SE or AP10-602. This study will enroll 70 healthy males and non-pregnant females subjects, aged 18 to 49. Subjects who meet all eligibility criteria will be randomized to ID93 alone, ID93 + GLA-SE, or ID93 + AP10-602 at either dose level. Study injections will be performed and subjects will be observed in clinic for 30 minutes. All subjects will complete a written subject memory aid that solicits local and systemic reactogenicity adverse events for 7 days following each study injection. After subjects are reevaluated to ensure they continue to meet eligibility criteria they will undergo second and third study injections on Days 29 and 57. General safety will be evaluated on Days 1, 3, 8, 29, 31, 36, 57, 59, 64, 71, 85, 169, and 422 for each subject. The occurrence of serious adverse events and the new onset of any adverse events of special interest (AESI) will be collected throughout the study period (approximately 422 days). Each subject's duration of participation will be about 15 months. The Primary Objective is : To evaluate the safety and tolerability of 10 µg ID93 + 5 or 10 µg AP10-602 compared to 10 µg ID93 + 5 µg GLA-SE and 10 µg ID93 alone following three consecutive intramuscular injections administered on Days 1, 29 and 57. The Secondary Objective is: To assess the immunogenicity of 10 µg ID93 + 5 or 10 µg AP10-602 compared to 10 µg ID93 + 5 µg GLA-SE and 10 µg ID93 alone by quantifying T cell responses and IgG antibody responses to ID93 at specified time points.

Conditions
Tuberculosis
Being tested
AP10-602, GLA-SE, ID93
Keywords
adjuvants, AP10-602, GLA-SE, ID93, Tuberculosis, vaccine
Medical subject headings
Tuberculosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AP10-602Other

    AP10-602 contains GLA formulated with liposomes and an additional immunological adjuvant. The ID93 (10 mcg) + AP10-602 (5 mcg) arm will receive intervention on days 1, 29 and 57. The ID93 (10 mcg) + AP10-602 (10 mcg) arm will receive intervention on days 1, 29 and 57.

  • GLA-SEBiological

    Glucopyranosyl Lipid A- Stable oil-in-water emulsion (GLA-SE). The ID93 (10 mcg) + GLA-SE (5 mcg) arm will receive intervention on days 1, 29 and 57

  • ID93Biological

    ID93 is a fusion polyprotein comprising four Mtb antigens (Rv2608, Rv3619, Rv3620, Rv1813). All arms will receive 10 mcg ID93 IM on days 1, 29 and 57

Study groups in NCT02508376
Study groupRoleWhat they receive
ID93 (10 mcg) + AP10-602 (10 mcg)ExperimentalN=20 subjects will receive intervention on Days 1, 29, 57
Receives: Other: AP10-602; Biological: ID93
ID93 (10 mcg) + AP10-602 (5 mcg)ExperimentalN=20 subjects will receive intervention on Days 1, 29, 57
Receives: Other: AP10-602; Biological: ID93
ID93 (10 mcg) + GLA-SE (5 mcg)ExperimentalN=20 subjects will receive intervention on Days 1, 29, 57
Receives: Biological: GLA-SE; Biological: ID93
ID93 (10 mcg) aloneExperimentalN=10 subjects will receive intervention on Days 1, 29, 57
Receives: Biological: ID93

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The number of serious adverse events considered related to the study injection reported at any point during the study period.

    Measured: Day 1 through Day 422

  2. The number of subjects experiencing solicited injection site reactions within 7 days following study injection.

    Measured: 7 days following each study injection

  3. The number of subjects experiencing solicited systemic reactions within 7 days following study injection.

    Measured: 7 days following each study injection

  4. The number of subjects spontaneously reporting adverse events considered related to the study injection at any point during the study period.

    Measured: Day 1 through Day 422

Secondary outcomes (4)
  1. Mean fold change from baseline (Day 1) in IgG antibody responses to ID93 on Day 85.

    Measured: Day 1 and Day 85

  2. Percentage of CD4 and CD8 T cells producing 1 or more cytokines (IFN-gamma, TNF and IL-2) simultaneously in response to stimulation with the ID93 antigen as measured by intracellular cytokine staining at Day 71 relative to baseline (Day 1).

    Measured: Day 1 and Day 71

  3. The magnitude of Th1 and Th2 cytokine production in PBMCs in response to the ID93 antigen relative to baseline (Day 1) at Day 71, as assayed by Luminex.

    Measured: Day 1 and Day 71

  4. The proportion of subjects with at least a 4-fold increase in IgG antibody responses to ID93 on Day 85 relative to baseline (Day 1).

    Measured: Day 1 through Day 85

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jul 2015 (estimated)
  2. Study start22 Oct 2015
  3. Primary completion31 Aug 2017
  4. Study completion31 Aug 2017

Resources

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
Double blind
Who is masked
Participant, Investigator
Enrolment
70 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02508376
Sponsor's protocol ID
12-0109
Other IDs
HHSN272201300020I
Status last verified
5 Apr 2017
First submitted
23 Jul 2015
Last updated
15 Sep 2017
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing AP10-602, GLA-SE and ID93 in people with Tuberculosis, 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 1 inclusion and 1 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 15 Sep 2017. 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?

The number of serious adverse events considered related to the study injection reported at any point during the study period. (time frame: Day 1 through Day 422). 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 15 Sep 2017.

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