Phase 2a ID93 + GLA-SE Vaccine Trial in TB Patients After Treatment Completion

• Sponsor: IDRI (Other)
• Overall Status: Completed
• CT.gov ID: NCT02465216
• Collaborator: Wellcome Trust (Other), South African Tuberculosis Vaccine Initiative (Other)
• Enrollment: 60
• Locations: 3
• Arms: 5
• Duration (Months): 19.1
• Patients Per Site: 20
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and immunogenicity of ID93 + GLA-SE vaccine when administered to adult pulmonary Tuberculosis (TB) patients, following successful completion of TB treatment with confirmed bacteriologic cure, in preparation for a future Phase 2b prevention of TB recurrence trial in the same population.

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Tuberculosis	Other: Placebo; Biological: ID93 + GLA-SE	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase 2A, Randomized, Double-Blind, Placebo-Controlled, Clinical Trial to Evaluate the Safety and Immunogenicity of the ID93 + GLA-SE Vaccine in HIV Uninfected Adult TB Patients After Treatment Completion
• Study Start Date: Jun 1, 2015
• Actual Primary Completion Date: Jan 1, 2017
• Actual Study Completion Date: Jan 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 2 mcg ID93 + 2 mcg GLA-SE Vaccine Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. Low dose of antigen and low dose of adjuvant.	Biological: ID93 + GLA-SE; ID93 + GLA-SE
Experimental: 10 mcg ID93 + 2 mcg GLA-SE Vaccine Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. High dose of antigen and low dose of adjuvant.	Biological: ID93 + GLA-SE; ID93 + GLA-SE
Experimental: 2 mcg ID93 + 5 mcg GLA-SE Vaccine Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. Low dose of antigen and high dose of adjuvant. Placebo injection at Day 28 to maintain blind with the 3 dose arm.	Biological: ID93 + GLA-SE; ID93 + GLA-SE
Placebo Comparator: Placebo Two intramuscular injections of normal saline at Days 0 and 56, or Days 0, 28, and 56.	Other: Placebo; Placebo
Experimental: 2 mcg ID93 + 5 mcg GLA-SE Vaccine 3 doses Three intramuscular injections of ID93 + GLA-SE at Days 0, 28, and 56. Low dose of antigen and high dose of adjuvant.	Biological: ID93 + GLA-SE; ID93 + GLA-SE

Outcome Measures

Primary Outcome Measures

1. Number of Adverse Events [224 days]

   Safety outcomes will include solicited adverse events within 7 days and unsolicited adverse events within 28 days after each study injection; and serious adverse events after the first study injection until end of study follow-up.

Secondary Outcome Measures

1. Immunogenicity Responder Rate [Day 70]

   Immunogenicity will be evaluated by measuring humoral and cellular responses to ID93 + GLA-SE at Day 70.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Males and females 18 to 60 years of age.

2. Subjects must have been successfully treated, i.e., completed the scheduled course of TB treatment as per the prevailing South African national guidelines, for MTB culture-confirmed, drug sensitive pulmonary TB, as evidenced by a record of positive liquid MTB culture with formal drug sensitivity testing (DST) and/or by Xpert MTB/RIF test at baseline.

3. Must have two separate samples showing bacteriologic confirmation of cure - defined in the first instance as Xpert MTB/RIF test negative, or, if Xpert MTB/RIF positive, as MTB liquid culture negative - on two successive occasions at least 30 days apart. Subjects who are sputum unproductive will be deemed Xpert MTB/RIF and MTB liquid culture negative.

4. Female subjects of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test on the day of each study injection, must not be breast-feeding, and be willing to avoid pregnancy for 3 months following first study injection. Women physically capable of pregnancy (not sterilized and still menstruating or within 1 year of the last menses if menopausal) in sexual relationships with men must use an acceptable method of avoiding pregnancy during this period. Acceptable methods of avoiding pregnancy include a sterile sexual partner, sexual abstinence (not engaging in sexual intercourse), hormonal contraceptives (oral, injection, transdermal patch, or implant), vaginal ring, intrauterine device (IUD), or the combination of a condom or diaphragm with spermicide gel.

5. The following screening laboratory values must be within the laboratory reference range or, if abnormal, deemed not clinically significant and less than Grade 2 severity on the FDA Toxicity Scale, as determined by the PI and LMM or Sponsor Medical Advisor: ALT, AST, total bilirubin, creatinine, total WBC count, hemoglobin, and platelet count.

6. The HIV 1/2 antibody serology tests must be negative.

7. Must give informed consent, be able and willing to make all evaluation visits, be reachable by telephone or personal contact by the study site personnel, and be willing to remain in the study area for the duration of the trial.

Exclusion Criteria:

1. TB treatment failure, as evidenced by clinical diagnosis or a positive MTB liquid culture at month 4 or 5 after starting treatment. A positive MTB liquid culture at, or after, end of treatment would exclude subjects from receiving further study injections.

2. Previous course of TB treatment completed within 5 calendar years prior to obtaining baseline diagnostic sputum samples.

3. Receipt of any investigational products or investigational drug in the past 6 months or investigational vaccine ever.

4. Treatment with immunosuppressive drugs (e.g., oral or injected steroids, such as prednisone; high dose inhaled steroids) in the past 6 months. Topical steroids would be allowable.

5. Received incomplete or investigational, or non-standard TB drug regimen, other than the prevailing current South African national guideline as reference standard, or poor adherence to TB treatment regimen.

6. Diagnosed with rifampicin-resistant MTB strain (by Xpert MTB/RIF and/or culture and formal DST).

7. History of autoimmune disease or other causes of immunosuppressive states.

8. History or evidence of any acute or chronic illness (including diabetes mellitus, asthma), medical or surgical condition, or chronic heavy ethanol or drug use, or use of medication that, in the opinion of the Principal Investigator, may interfere with the evaluation of the safety or immunogenicity of the vaccine.

9. Subjects with a history of previous anaphylaxis or severe allergic reaction to vaccines, eggs, or unknown allergens.

10. Subjects who are unlikely to cooperate with the requirements of the study protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	TASK Applied Sciences	Cape Town		South Africa	7530
2	Desmond Tutu HIV Centre (DTHC)	Cape Town		South Africa	7750
3	South African Tuberculosis Vaccine Initiative (SATVI)	Worcester		South Africa	6850

Sponsors and Collaborators

• IDRI
• Wellcome Trust
• South African Tuberculosis Vaccine Initiative

Investigators

• Principal Investigator: Mark Hatherill, MD, South African Tuberculosis Vaccine Initiative

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: IDRI
• ClinicalTrials.gov Identifier: NCT02465216
• Other Study ID Numbers: IDRI-TBVPX-203
• First Posted: Jun 8, 2015
• Last Update Posted: Mar 12, 2019
• Last Verified: Feb 1, 2019

• Keywords provided by IDRI: Tuberculosis; TB; Pulmonary; Vaccine; Adjuvant
• Additional relevant MeSH terms: Tuberculosis; Tuberculosis, Pulmonary

Study Results

Participant Flow

Arm/Group Title	2 mcg ID93 + 2 mcg GLA-SE Vaccine	10 mcg ID93 + 2 mcg GLA-SE Vaccine	2 mcg ID93 + 5 mcg GLA-SE Vaccine	2 mcg ID93 + 5 mcg GLA-SE Vaccine 3 Doses	Placebo
Arm/Group Description	Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. Low dose of antigen and low dose of adjuvant. ID93 + GLA-SE: ID93 + GLA-SE	Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. High dose of antigen and low dose of adjuvant. ID93 + GLA-SE: ID93 + GLA-SE	Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. Low dose of antigen and high dose of adjuvant. Placebo injection at Day 28 to maintain blind with the 3 dose arm. ID93 + GLA-SE: ID93 + GLA-SE	Three intramuscular injections of ID93 + GLA-SE at Days 0, 28, and 56. Low dose of antigen and high dose of adjuvant. ID93 + GLA-SE: ID93 + GLA-SE	Two intramuscular injections of normal saline at Days 0 and 56, or Days 0, 28, and 56. Placebo: Placebo
Period Title: Overall Study
STARTED	15	5	14	14	12
COMPLETED	12	5	13	12	9
NOT COMPLETED	3	0	1	2	3

Baseline Characteristics

Arm/Group Title	2 mcg ID93 + 2 mcg GLA-SE Vaccine	10 mcg ID93 + 2 mcg GLA-SE Vaccine	2 mcg ID93 + 5 mcg GLA-SE Vaccine	2 mcg ID93 + 5 mcg GLA-SE Vaccine 3 Doses	Placebo	Total
Arm/Group Description	Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. Low dose of antigen and low dose of adjuvant. ID93 + GLA-SE: ID93 + GLA-SE	Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. High dose of antigen and low dose of adjuvant. ID93 + GLA-SE: ID93 + GLA-SE	Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. Low dose of antigen and high dose of adjuvant. Placebo injection at Day 28 to maintain blind with the 3 dose arm. ID93 + GLA-SE: ID93 + GLA-SE	Three intramuscular injections of ID93 + GLA-SE at Days 0, 28, and 56. Low dose of antigen and high dose of adjuvant. ID93 + GLA-SE: ID93 + GLA-SE	Two intramuscular injections of normal saline at Days 0 and 56, or Days 0, 28, and 56. Placebo: Placebo	Total of all reporting groups
Overall Participants	15	5	14	14	12	60
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	15 100%	5 100%	14 100%	14 100%	12 100%	60 100%
>=65 years	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	11 73.3%	3 60%	7 50%	2 14.3%	4 33.3%	27 45%
Male	4 26.7%	2 40%	7 50%	12 85.7%	8 66.7%	33 55%
Race/Ethnicity, Customized (Count of Participants)
African Mixed Race	10 66.7%	1 20%	11 78.6%	7 50%	8 66.7%	37 61.7%
Black African	5 33.3%	4 80%	3 21.4%	7 50%	4 33.3%	23 38.3%
Region of Enrollment (Count of Participants)
South Africa	15 100%	5 100%	14 100%	14 100%	12 100%	60 100%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	20.6 (2.32)	22.8 (5.4)	19.6 (2.38)	21.4 (4.92)	21.4 (1.94)	20.9 (3.39)

Outcome Measures

1. Primary Outcome

Title	Number of Adverse Events
Description	Safety outcomes will include solicited adverse events within 7 days and unsolicited adverse events within 28 days after each study injection; and serious adverse events after the first study injection until end of study follow-up.
Time Frame	224 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2 mcg ID93 + 2 mcg GLA-SE Vaccine	10 mcg ID93 + 2 mcg GLA-SE Vaccine	2 mcg ID93 + 5 mcg GLA-SE Vaccine	2 mcg ID93 + 5 mcg GLA-SE Vaccine 3 Doses	Placebo
Arm/Group Description	Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. Low dose of antigen and low dose of adjuvant. ID93 + GLA-SE: ID93 + GLA-SE	Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. High dose of antigen and low dose of adjuvant. ID93 + GLA-SE: ID93 + GLA-SE	Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. Low dose of antigen and high dose of adjuvant. Placebo injection at Day 28 to maintain blind with the 3 dose arm. ID93 + GLA-SE: ID93 + GLA-SE	Three intramuscular injections of ID93 + GLA-SE at Days 0, 28, and 56. Low dose of antigen and high dose of adjuvant. ID93 + GLA-SE: ID93 + GLA-SE	Two intramuscular injections of normal saline at Days 0 and 56, or Days 0, 28, and 56. Placebo: Placebo
Measure Participants	15	5	14	14	12
Local Injection Site Reactions	5 33.3%	4 80%	10 71.4%	8 57.1%	3 25%
Solicited Systemic Reactions	1 6.7%	0 0%	1 7.1%	1 7.1%	0 0%
Any Adverse Event	12 80%	5 100%	13 92.9%	12 85.7%	9 75%
Serious Adverse Events	0 0%	0 0%	0 0%	0 0%	2 16.7%

2. Secondary Outcome

Title	Immunogenicity Responder Rate
Description	Immunogenicity will be evaluated by measuring humoral and cellular responses to ID93 + GLA-SE at Day 70.
Time Frame	Day 70

Outcome Measure Data

Analysis Population Description

Those participants without major protocol deviations and with samples available for analysis.

Arm/Group Title	2 mcg ID93 + 2 mcg GLA-SE Vaccine	10 mcg ID93 + 2 mcg GLA-SE Vaccine	2 mcg ID93 + 5 mcg GLA-SE Vaccine	2 mcg ID93 + 5 mcg GLA-SE Vaccine 3 Doses	Placebo
Arm/Group Description	Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. Low dose of antigen and low dose of adjuvant. ID93 + GLA-SE: ID93 + GLA-SE	Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. High dose of antigen and low dose of adjuvant. ID93 + GLA-SE: ID93 + GLA-SE	Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. Low dose of antigen and high dose of adjuvant. Placebo injection at Day 28 to maintain blind with the 3 dose arm. ID93 + GLA-SE: ID93 + GLA-SE	Three intramuscular injections of ID93 + GLA-SE at Days 0, 28, and 56. Low dose of antigen and high dose of adjuvant. ID93 + GLA-SE: ID93 + GLA-SE	Two intramuscular injections of normal saline at Days 0 and 56, or Days 0, 28, and 56. Placebo: Placebo
Measure Participants	13	5	13	11	11
IgG antibody responder rate	12 80%	5 100%	13 92.9%	11 78.6%	0 0%
CD4 T cell responder rate (whole antigen stim)	4 26.7%	2 40%	10 71.4%	1 7.1%	1 8.3%

Adverse Events

Time Frame	224 days
Arm/Group Title	2 mcg ID93 + 2 mcg GLA-SE Vaccine		10 mcg ID93 + 2 mcg GLA-SE Vaccine		2 mcg ID93 + 5 mcg GLA-SE Vaccine		2 mcg ID93 + 5 mcg GLA-SE Vaccine 3 Doses		Placebo
Arm/Group Description	Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. Low dose of antigen and low dose of adjuvant. ID93 + GLA-SE: ID93 + GLA-SE		Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. High dose of antigen and low dose of adjuvant. ID93 + GLA-SE: ID93 + GLA-SE		Two intramuscular injections of ID93 + GLA-SE at Days 0 and 56. Low dose of antigen and high dose of adjuvant. Placebo injection at Day 28 to maintain blind with the 3 dose arm. ID93 + GLA-SE: ID93 + GLA-SE		Three intramuscular injections of ID93 + GLA-SE at Days 0, 28, and 56. Low dose of antigen and high dose of adjuvant. ID93 + GLA-SE: ID93 + GLA-SE		Two intramuscular injections of normal saline at Days 0 and 56, or Days 0, 28, and 56. Placebo: Placebo
All Cause Mortality
	2 mcg ID93 + 2 mcg GLA-SE Vaccine		10 mcg ID93 + 2 mcg GLA-SE Vaccine		2 mcg ID93 + 5 mcg GLA-SE Vaccine		2 mcg ID93 + 5 mcg GLA-SE Vaccine 3 Doses		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/5 (0%)		0/14 (0%)		0/14 (0%)		1/12 (8.3%)
Serious Adverse Events
	2 mcg ID93 + 2 mcg GLA-SE Vaccine		10 mcg ID93 + 2 mcg GLA-SE Vaccine		2 mcg ID93 + 5 mcg GLA-SE Vaccine		2 mcg ID93 + 5 mcg GLA-SE Vaccine 3 Doses		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/5 (0%)		0/14 (0%)		0/14 (0%)		2/12 (16.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chest wall tumour	0/15 (0%)	0	0/5 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/12 (8.3%)	1
Psychiatric disorders
Delirium tremens	0/15 (0%)	0	0/5 (0%)	0	0/14 (0%)	0	0/14 (0%)	0	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	2 mcg ID93 + 2 mcg GLA-SE Vaccine		10 mcg ID93 + 2 mcg GLA-SE Vaccine		2 mcg ID93 + 5 mcg GLA-SE Vaccine		2 mcg ID93 + 5 mcg GLA-SE Vaccine 3 Doses		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/15 (80%)		5/5 (100%)		13/14 (92.9%)		12/14 (85.7%)		9/12 (75%)
General disorders
Injection site erythema	0/15 (0%)	0	0/5 (0%)	0	4/14 (28.6%)	5	1/14 (7.1%)	1	0/12 (0%)	0
Injection site induration	1/15 (6.7%)	1	0/5 (0%)	0	3/14 (21.4%)	4	3/14 (21.4%)	3	0/12 (0%)	0
Injection site pain	5/15 (33.3%)	6	4/5 (80%)	4	10/14 (71.4%)	16	7/14 (50%)	13	3/12 (25%)	3
Infections and infestations
Tonsilitis	0/15 (0%)		0/5 (0%)		3/14 (21.4%)		0/14 (0%)		0/12 (0%)
URTI	3/15 (20%)		1/5 (20%)		3/14 (21.4%)		1/14 (7.1%)		3/12 (25%)
Investigations
ALT increased	2/15 (13.3%)		0/5 (0%)		1/14 (7.1%)		3/14 (21.4%)		2/12 (16.7%)
Blood bilirubin increased	1/15 (6.7%)		0/5 (0%)		1/14 (7.1%)		0/14 (0%)		1/12 (8.3%)
Haemoglobin decreased	1/15 (6.7%)		1/5 (20%)		1/14 (7.1%)		0/14 (0%)		0/12 (0%)
WBC count decreased	0/15 (0%)		1/5 (20%)		2/14 (14.3%)		2/14 (14.3%)		0/12 (0%)
WBC count increased	1/15 (6.7%)		0/5 (0%)		1/14 (7.1%)		1/14 (7.1%)		1/12 (8.3%)
Nervous system disorders
Headache	1/15 (6.7%)		2/5 (40%)		1/14 (7.1%)		0/14 (0%)		3/12 (25%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	0/15 (0%)		1/5 (20%)		2/14 (14.3%)		0/14 (0%)		0/12 (0%)
Vascular disorders
Hypertension	1/15 (6.7%)		0/5 (0%)		1/14 (7.1%)		1/14 (7.1%)		0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.