Clinical trial NCT02066428: A Phase I Randomized Placebo-Controlled, Double-Blind Study to Evaluate Safety and Immunogenicity of AERAS-404 Administered as Different Amounts of Antigen and Adjuvant Combinations in HIV-Negative BCG-Vaccinated Adults Without Evidence of Tuberculosis Infection
Official title: A Phase I Randomized Placebo-Controlled, Double-Blind Study to Evaluate Safety and Immunogenicity of AERAS-404 Administered as Different Amounts of Antigen and Adjuvant Combinations in HIV-Negative BCG-Vaccinated Adults Without Evidence of Tuberculosis Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Tuberculosis
Keywords: BCG Vaccinated
HIV Negative
Lead sponsor: Aeras
Sponsor class: OTHER
Collaborators: name: Statens Serum Institut
First posted: 2014-02-19
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Phase I, randomized, double blinded, Placebo-controlled, immunogenicity and dose-range finding study of AERAS-404 in Bacille Calmette-Guerin (BCG) healthy adult male and sterile females.

Detailed description: This ia a Phase I, randomized, placebo-controlled, double-blind study in three groups of healthy adult males or sterile females who are BCG-vaccinated, HIV-negative, and have no evidence of tuberculosis infection.

Sixty-four subjects assigned to one of eight treatment groups to receive one of four different antigen/adjuvant combinations of study vaccine, or placebo control. Within each study group, subjects will be randomized to receive either a single-dose antigen/adjuvant regimen of study vaccine (vaccination with study vaccine on Study Day 0 followed by vaccination with placebo control on Study Day 56) or a two-dose antigen/adjuvant regimen of study vaccine (vaccination with study vaccine on Study Days 0 and 56).

All subjects will be followed for safety and immunogenicity evaluations for 182 days.

The sample sizes specified for each study group were selected because they are judged to be adequate for preliminary safety and immunogenicity evaluations for a Phase I study rather than for statistical reasons. If no SAE are observed among 56 subjects receiving active study vaccine, an approximation to the upper 95% confidence bound on the rate of SAE occurrence would be 5.4%.

Eligibility criteria: Inclusion Criteria:

1. Male or female
2. Age 18 through 50 years on Study Day 0
3. Completed wriiten Informed Consent
4. BCG vaccination at least 5 years ago,
5. General good health, confirmed by medical history
6. (BMI) between 19 and 33 (kg/m2)
7. Has ability to complete follow-up period of 182 days as required
8. Females must be physically incapable of conception
9. Avoiding elective surgery for the duration of the study
10. Stay in contact with the investigative site for the duration of the study
11. Complete simultaneous enrollment in Aeras Vaccine Development Registry protocol

Exclusion Criteria:

1. Acute illness on the day of randomization
2. Oral temperature \>=37.5 degree Celcius on the day of randomization
3. Evidence of significant active infection
4. Used immunosuppressive medication within 42 days before entry into the study
5. Received immunoglobulin or blood products within 42 days before entry into the study
6. Received any investigational drug therapy or investigational vaccine within 182 days
7. Received inactivated influenza vaccine or inactivated tick-borne encephalitis vaccine within 14 days before entry into the study.
8. Current chronic drug therapy including hormone replacement such as thyroxin, insulin, etc.
9. History or laboratory evidence of any past, present or future possible immunodeficiency state which will include any laboratory indication of virus type 1 (HIV-1) infection
10. History of allergic disease or reactions, including eczema.
11. Previous medical history that may compromise safety of subject
12. Evidence of new acute illness that may compromise safety of subject
13. Evidence of chronic hepatitis
14. Inability to discontinue daily medication except contraception
15. History of alcohol or drug abuse within 2yrs
16. Tobacco or cannabis smoking three
17. Positive urine test for illicit drugs
18. History or evidence of any systemic disease on physical examination
19. History of active TB
20. Shared residence within 1 year with an individual on anti-TB treatment
21. All females: nursing
22. Abnormal hemoglobin,hematocrit etc drawn within 36 hours prior to randomization
23. Laboratory test evidence of Mtb infection
24. History of positive tuberculin skin test within past 10 years
25. Received a tuberculin skin test within 3 years
26. History of autoimmune disease

Primary outcomes:
measure: Evaluate the safety of one or two injections of two AERAS 404 antigen amounts administered with three different amounts of adjuvant
timeFrame: All subjects will be followed for safety and immunogenicity evaluations for 182 days. A total of eleven clinic visits are planned (excluding screening) for all subjects
Secondary outcomes:
measure: Evaluate the immunogenicity of one or two injections of two AERAS 404 antigen amounts administered with three different amounts of adjuvant.
timeFrame: all subjects will have immunology samples taken at 9 time points over 182 days
Other outcomes:
Locations:
city: Huddinge
country: Sweden
facility: Karolinska Institutet, Karolinska University Hospital
state: Stockholm
Study officials:
affiliation: Aeras
name: Zhongkai SHI, MD
role: STUDY_DIRECTOR
affiliation: Karolinska Institutet
name: Jan Andersson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Norrby M, Vesikari T, Lindqvist L, Maeurer M, Ahmed R, Mahdavifar S, Bennett S, McClain JB, Shepherd BM, Li D, Hokey DA, Kromann I, Hoff ST, Andersen P, de Visser AW, Joosten SA, Ottenhoff THM, Andersson J, Brighenti S. Safety and immunogenicity of the novel H4:IC31 tuberculosis vaccine candidate in BCG-vaccinated adults: Two phase I dose escalation trials. Vaccine. 2017 Mar 14;35(12):1652-1661. doi: 10.1016/j.vaccine.2017.01.055. Epub 2017 Feb 17.