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

NCT02508376 | Completed Phase 1 FDA Drug

• 2 other identifiers: 12-0109HHSN272201300020I
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Tuberculosis

Keywords

adjuvants; AP10-602; GLA-SE; ID93; Tuberculosis; vaccine

Outcome Measures

Primary Outcomes (4)

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

  Day 1 through Day 422

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

  7 days following each study injection

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

  7 days following each study injection

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

  Day 1 through Day 422

Secondary Outcomes (4)

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

  Day 1 and Day 85

• 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).

  Day 1 and Day 71

• 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.

  Day 1 and Day 71

• 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).

  Day 1 through Day 85

Study Arms (4)

ID93 (10 mcg) + AP10-602 (10 mcg)

EXPERIMENTAL

N=20 subjects will receive intervention on Days 1, 29, 57

Other: AP10-602; Biological: ID93

ID93 (10 mcg) + AP10-602 (5 mcg)

EXPERIMENTAL

N=20 subjects will receive intervention on Days 1, 29, 57

Other: AP10-602; Biological: ID93

ID93 (10 mcg) + GLA-SE (5 mcg)

EXPERIMENTAL

N=20 subjects will receive intervention on Days 1, 29, 57

Biological: GLA-SE; Biological: ID93

ID93 (10 mcg) alone

EXPERIMENTAL

N=10 subjects will receive intervention on Days 1, 29, 57

Biological: ID93

Interventions

AP10-602 OTHER

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.

ID93 (10 mcg) + AP10-602 (10 mcg); ID93 (10 mcg) + AP10-602 (5 mcg)

GLA-SE BIOLOGICAL

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

ID93 (10 mcg) + GLA-SE (5 mcg)

ID93 BIOLOGICAL

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

ID93 (10 mcg) + AP10-602 (10 mcg); ID93 (10 mcg) + AP10-602 (5 mcg); ID93 (10 mcg) + GLA-SE (5 mcg); ID93 (10 mcg) alone

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \. 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

University of Iowa - Vaccine Research and Education Unit

Iowa City, Iowa, 52242-2600, United States

Location

MeSH Terms

Conditions

Tuberculosis

Interventions

glucopyranosyl lipid-A

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2015
• First Posted: July 24, 2015
• Study Start: October 22, 2015
• Primary Completion: August 31, 2017
• Study Completion: August 31, 2017
• Last Updated: September 15, 2017

Record last verified: 2017-04-05

Locations

US (1)