Live Attenuated ETEC Vaccine ACE527 With and Without dmLT Adjuvant in Adults

NCT01739231 | Completed Phase 1 Results DMC

• 1 other identifier: VAC 006
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study about an experimental (investigational) oral ETEC vaccine (ACE527). ACE527 is a live attenuated vaccine that is being made to prevent disease from enterotoxigenic Escherichia coli (ETEC), which causes watery diarrhea, largely in children living in developing countries and in travelers to those countries. This research study is also testing an investigational adjuvant called dmLT. An adjuvant is something that is added to a vaccine to make it work better. The purpose of this study is two-fold. First, Part A aims to find out if the vaccine by itself or the vaccine combined with the adjuvant is safe, tolerable, and initiates an immune response. Second, Part B aims to find out if the vaccine by itself or the vaccine combined with the adjuvant prevents diarrheal disease when challenged with ETEC H10407. About 60 healthy adults, ages 18-50, will participate in Part A, and they will be required to stay in the research facility for several nights for the first dose, but will not be required to stay overnight for the second and third doses. Participants will be assigned to receive either the vaccine alone, the vaccine with adjuvant, or placebo by mouth. Study procedures include: stool samples, blood samples, and documentation of side effects. Participants will be involved in study related procedures for about 8 months. Interested volunteers from Part A will along with volunteers who were never vaccinated in Part A will return to participate in Part B. These volunteers will be required to stay overnight in the research facility for several nights after challenge, after which they will be treated with antibiotics and sent home. Study procedures include stool samples, blood samples, and documentation of infection with ETEC H10407. If the vaccine with/without adjuvant is effective, the volunteers should not development diarrhea, but if the vaccine with/without adjuvant is not effective, the volunteers will have diarrhea for a few days.

Conditions

Diarrhea

Outcome Measures

Primary Outcomes (40)

• Part A: Number of Serious Adverse Events and Adverse Events Leading to Withdrawal

  Unsolicited adverse events were collected throughout Part A of the study, were graded for severity, and assessed for relationship to vaccine. Withdrawal from the study due to adverse event was determined at the discretion of the study staff.

  up to 1 month after last vaccination (3 months)

• Part A: Number of Participants Experiencing Unsolicited Adverse Events, by Severity and Relationship to Vaccination

  Unsolicited adverse events were collected throughout Part A of the study, were graded for severity, and assessed for relationship to vaccine. Generally, mild severity is discomfort with no disruption of normal daily activities and relieved with or without symptomatic treatment; moderate severity is discomfort sufficient to reduce or affect normal daily activity somewhat and only partially relieved with symptomatic treatment; and severe is discomfort sufficient to reduce or affect normal daily activity considerably; prevents regular activities, and not relieved with symptomatic treatment. Additional description of severity for diarrhea, body temperature, and vomiting is described in the protocol.

  up to 1 month after last vaccination (3 months)

• Part A: Number of Solicited Reactions

  Solicited reactions were collected 1 week after each vaccination.

  up to 1 week after each vaccination (at 0, 1, and 2 months)

• Part A: Number and Percentage of Subjects With Positive Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

  Defined as a four-fold rise or greater in geometric mean titer.

  Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

• Part A: Geometric Mean Fold Change in Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

  Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

• Part A: Geometric Mean Titer of Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

  Pre and day 7 post all vaccinations; day 3 post-vaccination 1 and 2; week 4 post vaccination 3

• Part A: Number and Percentage of Subjects With Positive Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

  Defined as a four-fold rise or greater in geometric mean titer.

  Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

• Part A: Geometric Mean Fold Change in Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

  Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

• Part A: Geometric Mean Titer of Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

  Pre and day 7 post all vaccinations; day 3 post-vaccination 1 and 2; week 4 post vaccination 3

• Part A: Number and Percentage of Subjects With Positive Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

  Defined as a four-fold rise or greater in geometric mean titer.

  Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

• Part A: Geometric Mean Fold Change in Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

  Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

• Part A: Geometric Mean Titer of Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

  Pre all vaccinations; day 3 post-vaccination 1 and 2; day 7 post all vaccinations; 4 weeks post-vaccination 3

• Part A: Number and Percentage of Subjects With Positive Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

  Defined as a four-fold rise or greater in geometric mean titer.

  Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

• Part A: Geometric Mean Fold Change in Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

  Vaccination 1 Day 3 and 7; Vaccination 2 pre-vaccination, Day 3, and Day 7; Vaccination 3 pre-vaccination, Day 7, and Week 4

• Part A: Geometric Mean Titer of Antibody in Lymphocyte Supernatant (ALS) Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

  Pre and day 7 post all vaccinations; day 3 post-vaccination 1 and 2; week 4 post vaccination 3

• Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

  Defined as a 2.5-fold rise or greater in geometric mean titer.

  Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

• Part A: Geometric Mean Fold Change in Antibody in Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

  Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

• Part A: Geometric Mean Titer of Antibody in Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

  Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

• Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

  Defined as a 2.5-fold rise or greater in geometric mean titer.

  Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

• Part A: Geometric Mean Fold Change in Serum ELISA Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

  Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

• Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin A (IgA) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

  Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

• Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

  Defined as a 2.5-fold rise or greater in geometric mean titer.

  Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

• Part A: Geometric Mean Fold Change in Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

  Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

• Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 3 (CS3)

  Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

• Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

  Defined as a 2.5-fold rise or greater in geometric mean titer.

  Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

• Part A: Geometric Mean Fold Change in Antibody in Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

  Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

• Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin A (IgA) Response to E. Coli Surface Antigen 6 (CS6)

  Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

• Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

  Defined as a 2.5-fold rise or greater in geometric mean titer.

  Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

• Part A: Geometric Mean Fold Change in Antibody in Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

  Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

• Part A: Geometric Mean Titer of Antibody in Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Heat Labile Toxin B Subunit (LTB)

  Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

• Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin G (IgG) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

  Defined as a 2.5-fold rise or greater in geometric mean titer.

  Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

• Part A: Geometric Mean Fold Change in Serum ELISA Immunoglobulin G (IgG) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

  Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

• Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin G (IgG) Response to Enterotoxigenic Escherichia Coli (ETEC) Colonization Factor 1 (CFA/I)

  Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

• Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 3 (CS3)

  Defined as a 2.5-fold rise or greater in geometric mean titer.

  Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

• Part A: Geometric Mean Fold Change in Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 3 (CS3)

  Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

• Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 3 (CS3)

  Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

• Part A: Number and Percentage of Subjects With Positive Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 6 (CS6)

  Defined as a 2.5-fold rise or greater in geometric mean titer.

  Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

• Part A: Geometric Mean Fold Change in Antibody in Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 6 (CS6)

  Day 7 post-all vaccinations; pre-vaccination 2 and 3; week 4 post-vaccination 3

• Part A: Geometric Mean Titer of Serum ELISA Immunoglobulin G (IgG) Response to E. Coli Surface Antigen 6 (CS6)

  Pre and day 7 post all vaccinations; and 4 weeks post vaccination 3

• Part B: Number and Percentage of Subjects Experiencing Severe Diarrhea Following H10407 Challenge Strain

  Severe diarrhea was defined as \>800 grams of grade 3-5 stools passed over the 120-hour observation period. For episodes starting at or before 120 hours post-challenge, volunteers were followed to resolution and the total stool output weight was considered in determining whether a specific volunteer met the primary definition of severe diarrhea. The end of a diarrheal episode occurred when a volunteer did not pass any grade 3-5 stool in a 24-hour period. Grades were defined as follows: Grade 1: firm, formed (normal) Grade 2: soft, formed (normal) Grade 3: viscous opaque liquid or semi-liquid which assumes the shape of the container Grade 4: watery, non-viscous, opaque liquid which assumes the shape of the container Grade 5: clear or translucent, watery or mucoid liquid which assumes the shape of the container

  5 days

Secondary Outcomes (13)

• Part A: Number of Participants Shedding E. Coli on Qualification Plate

  Pre- and day 7 post-all vaccinations; and Day 3 post-vaccinations 1 and 2; and 4 weeks post vaccination 3

• Part A: Number of Participants With Positive Shedding Results for ACE527

  Pre- and day 7 post-all vaccinations; and Day 3 post-vaccinations 1 and 2; and 4 weeks post vaccination 3

• Number of Participants Shedding Vaccine Strains Included in ACE527

  3 days after the first and second vaccinations

• Part B: Number and Percentage of Subjects Experiencing Diarrhea of Any Severity

  5 days

• Part B: Mean Total Weight of Grade 3-5 Stools Passed Per Volunteer

  5 days

Study Arms (4)

ACE527 alone

EXPERIMENTAL

In Part A of the study, subjects were split into two cohorts whereby enrollment of the second cohort depended on the safety profile of the first cohort. In Part A, subjects received three oral doses of ACE527 at 0, 1, and 2 months. For Part B of the study, eligible subjects who expressed interest of the study were administered H10407 challenge strain 5-7 months after the three-dose vaccination series.

Biological: ACE527; Biological: H10407 challenge strain

ACE527 plus dmLT

EXPERIMENTAL

In Part A of the study, subjects were split into two cohorts whereby enrollment of the second cohort depended on the safety profile of the first cohort. In Part A, subjects received three oral doses of ACE527 with mucosal adjuvant (dmLT) at 0, 1, and 2 months. For Part B of the study, eligible subjects who expressed interest of the study were administered H10407 challenge strain 5-7 months after the three-dose vaccination series.

Biological: ACE527; Biological: dmLT; Biological: H10407 challenge strain

Control: Part A and B

ACTIVE COMPARATOR

In Part A of the study, subjects were split into two cohorts whereby enrollment of the second cohort depended on the safety profile of the first cohort. In Part A, subjects received three oral doses of CeraVacx placebo at 0, 1, and 2 months. For Part B of the study, eligible subjects who expressed interest of the study were administered H10407 challenge strain 5-7 months after the three-dose vaccination series.

Biological: CeraVacx placebo; Biological: H10407 challenge strain

Control: Part B only

ACTIVE COMPARATOR

Eligible participants were screened and administered H10407 challenge strain concurrently with other arms in Part B of the study. Their results for Part B are combined with that of the Control Arm in Part A, which received three oral doses of CeraVacx placebo.

Biological: H10407 challenge strain

Interventions

ACE527 BIOLOGICAL

3x10\^9 cfu ACE527 vaccine strain. Comprised of three genetically attenuated and engineered strains of E. coli, with antigen profiles covering a wide range of ETEC surface colonization factor antigens (CFA/I, CFA/II \[CS1, CS2, CS3\] and CFA/IV \[CS5, CS6\]) and also expressing LTB, the inactive subunit of LT (ETEC heat labile toxin). The constituent strains of ACE527 were: * ACAM2025: a live, attenuated, CFA/I, LTB positive strain * ACAM2022: a live, attenuated, CS5, CS6, LTB positive strain, and * ACAM2027: a live, attenuated, CS1, CS2, CS3, LTB positive strain.

ACE527 alone; ACE527 plus dmLT

dmLT BIOLOGICAL

A derivative of wild-type enterotoxigenic Escherichia coli heat-labile enterotoxin that has been genetically modified by replacing the arginine at amino acid position 192 with glycine and the leucine at amino acid position 211 with alanine (13). These two amino acid substitutions take place in proteolytic cleavage sites which are critical for activation of the secreted toxin molecules.

Also known as: LT(R192G/L211A)

ACE527 plus dmLT

CeraVacx placebo BIOLOGICAL

CeraVacx® is used to neutralize gastric acidity upon ingestion of vaccine. It was also used as the placebo in this study. CeraVacx® was prepared from the commercial product (Cera Products, Inc.); 9.5 grams were added to sterile water for each dose and mixed. Each dose contained 7 grams of rice syrup, 2 grams of sodium bicarbonate, and 0.5 grams of trisodium citrate.

Control: Part A and B

H10407 challenge strain BIOLOGICAL

Approximately 2 x 10\^7 cfu of the fully virulent ETEC strain. Previously administered to 91 volunteers at this challenge dose by the CIR clinical team over the previous 4 years in conjunction with other Phase 1/2b trials.

Also known as: ST+, LT+, CFA/I toxin

ACE527 alone; ACE527 plus dmLT; Control: Part A and B; Control: Part B only

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male and female healthy adults between 18 and 50 years of age at the time of enrollment.
• General good health, without clinically significant medical history, physical examination findings or clinical laboratory abnormalities per clinical judgment of PI.
• Negative pregnancy test at screening and before the first (V0), second (V28), and third vaccinations (V56) for female volunteers of childbearing potential. Females of childbearing potential must agree to use an efficacious hormonal or barrier method of birth control during the study. Abstinence is acceptable. Female volunteers unable to bear children must have this documented (e.g. tubal ligation or hysterectomy) or must have negative pregnancy tests.
• Willingness to participate in the study after all aspects of the protocol have been explained and written informed consent obtained.
• Completion of a training session and demonstrated comprehension of the protocol procedures and knowledge of ETEC associated illness by passing a written examination (70% pass score).
• Availability for the study duration, including all planned follow-up visits.
• Received at least 2 doses of ACE527 vaccine alone or in combination with 25 ug dmLT 4-6 months prior to challenge (Part B only)

You may not qualify if:

• Presence of a significant medical or psychiatric condition which in the opinion of the investigator precludes participation in the study. Some medical conditions which are adequately treated and stable would not preclude entry into the study. These conditions might include stable asthma controlled with inhalers or mild hypertension stably controlled with a single agent.
• Significant abnormalities in screening hematology, or serum chemistry as determined by PI or PI in consultation with the Medical Officer and sponsor.
• Presence in the serum of HIV antibody, HBsAg, or HCV antibody.
• Evidence of IgA deficiency (serum IgA \< 7 mg/dl or limit of detection of assay).
• Evidence of current excessive alcohol consumption or drug dependence.
• Volunteers whose Body Mass Index (BMI) is less than 19.0 or greater than 34.0 (kg/m2)
• Recent vaccination or receipt of an investigational product (within 30 days before vaccination).
• Intention to donate blood or blood products within one month following the completion of study participation (note: The Red Cross will not allow blood donations for 1 year following participation in an investigational research study).
• Any other criteria which, in the investigator's opinion, would compromise the ability of the volunteer to participate in the study, the safety of the study, or the results of the study
• Working as a food handler, in child-care or as a healthcare worker with direct patient contact.
• Have household contacts who are \<2 years old or \>80 years old or infirm or immunocompromised (for reasons including corticosteroid therapy, HIV infection, cancer chemotherapy, or other chronic debilitating disease).
• Abnormal stool pattern (fewer than 3 per week or more than 3 per day).
• Regular (≥ weekly) use of laxatives, antacids, or other agents to lower stomach acidity.
• Use of any medication known to affect the immune function (e.g., corticosteroids and others) within 30 days preceding the first vaccination or planned use during the active study period.
• Symptoms consistent with Traveler's Diarrhea concurrent with travel to countries where ETEC infection is endemic (most of the developing world) within two years prior to dosing, OR planned travel to endemic countries during the length of the study.

Sponsors & Collaborators

• PATH: lead

Study Sites (1)

Center for Immunization Research (CIR) at Johns Hopkins School of Public Health (JHSPH)

Baltimore, Maryland, 21224, United States

Location

Related Publications (1)

• Harro C, Louis Bourgeois A, Sack D, Walker R, DeNearing B, Brubaker J, Maier N, Fix A, Dally L, Chakraborty S, Clements JD, Saunders I, Darsley MJ. Live attenuated enterotoxigenic Escherichia coli (ETEC) vaccine with dmLT adjuvant protects human volunteers against virulent experimental ETEC challenge. Vaccine. 2019 Mar 28;37(14):1978-1986. doi: 10.1016/j.vaccine.2019.02.025. Epub 2019 Feb 21.

  PMID: 30797634 DERIVED

MeSH Terms

Conditions

Diarrhea

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Richard Walker
• Organization: PATH

rwalker@path.org

202-822-0033

Study Officials

• Clayton D Harro, MD, ScM

  Johns Hopkins Bloomberg School of Public Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part A of the study was masked to the participant, care provider, investigator, and outcomes assessor. Part B was open label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2012
• First Posted: December 3, 2012
• Study Start: September 1, 2012
• Primary Completion: October 1, 2013
• Study Completion: January 1, 2014
• Last Updated: February 12, 2019
• Results First Posted: December 21, 2018

Record last verified: 2019-01

Locations

US (1)