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Clinical Trial Results:
A phase II observer blind, randomised, controlled study to evaluate the safety, reactogenicity and immunogenicity of GSK Biologicals’ candidate tuberculosis vaccine GSK 692342 when administered to adults aged 18 to 59 years with TB disease.

Summary
EudraCT number	2012-001820-36
Trial protocol	EE
Global end of trial date	10 Apr 2014

Results information
Results version number	v2(current)
This version publication date	19 Mar 2016
First version publication date	22 May 2015
Other versions	v1
Version creation reason	New data added to full data set Data for secondary endpoints have been added.

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

114886

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GlaxoSmithKline Biologicals

Sponsor organisation address

Rue de l’Institut 89, Rixensart, Belgium, B-1330

Public contact

Clinical Disclosure Advisor, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com

Scientific contact

Clinical Disclosure Advisor, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Interim

Date of interim/final analysis

20 Mar 2015

Is this the analysis of the primary completion data?

Yes

Primary completion date

10 Apr 2014

Global end of trial reached?

Yes

Global end of trial date

10 Apr 2014

Was the trial ended prematurely?

Yes

Main objective of the trial

To assess the safety and reactogenicity of GSK Biologicals’ candidate TB vaccine M72/AS01E in the study population.

Protection of trial subjects

All subjects were supervised after vaccination/product administration with appropriate medical treatment readily available. Vaccines were administered by qualified and trained personnel. Vaccines were administered only to eligible subjects that had no contraindications to any components of the vaccines.

Background therapy

Evidence for comparator

Actual start date of recruitment

14 Nov 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Estonia: 36

Country: Number of subjects enrolled

Taiwan: 106

Worldwide total number of subjects

142

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

142

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

During the screening the following was performed: informed consent was obtained and signed from parents or guardians of subjects, check for inclusion/exclusion criteria and contraindications/precautions was performed, and medical history of subjects was collected. Prior to vaccination, subjects’ pre-vaccination body temperature was evaluated.

Period 1 title

Overall study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer

Blinding implementation details

During the course of the study, the vaccine recipient and those responsible for the evaluation of any study endpoints have been unaware of which vaccine was administered.

Are arms mutually exclusive

Yes

TB Treatment GSK 692342 Group

Arm description

Subjects having completed the intensive phase of treatment, i.e. 2 to 4 months post initiation of treatment, who received the GSK 692342 vaccine according to a 2-dose schedule at Months 0 and 1.

Arm type

Experimental

Investigational medicinal product name

GSK 692342

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses of vaccine were administered intramuscularly in the deltoid region of the arm, on a 0, 1 Months schedule

TB Treatment Saline Group

Arm description

Subjects having completed the intensive phase of treatment, i.e. 2 to 4 months post initiation of treatment who received a placebo (physiological saline) according to a 2-dose schedule at Months 0 and 1.

Arm type

Placebo

Investigational medicinal product name

Physiological Saline

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Doses were administered intramuscularly in the deltoid of the arm at Months 0 and 1

TB Treated GSK 692342 Group

Arm description

Subjects having successfully completed treatment for TB disease at least 1 year prior to the study, who during this study received the GSK 692342 vaccine according to a 2-dose schedule at Months 0 and 1

Arm type

Experimental

Investigational medicinal product name

GSK 692342

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses of vaccine were administered intramuscularly in the deltoid region of the arm, on a 0, 1 Months schedule

TB Treated Saline Group

Arm description

Subjects having successfully completed treatment for TB disease at least 1 year prior to the study, who in this study received a placebo (physiological saline) according to a 2-dose schedule at Months 0 and 1.

Arm type

Placebo

Investigational medicinal product name

Physiological Saline

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Doses were administered intramuscularly in the deltoid of the arm at Months 0 and 1

TB Naive GSK 692342 Group

Arm description

Subjects unaffected by tuberculosis who received the GSK 692342 vaccine according to a 2-dose schedule at Months 0 and 1.

Arm type

Experimental

Investigational medicinal product name

GSK 692342

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Two doses of vaccine were administered intramuscularly in the deltoid region of the arm, on a 0, 1 Months schedule

TB Naive Saline Group

Arm description

Subjects unaffected by tuberculosis who received a placebo (physiological saline) according to a 2-dose schedule at Months 0 and 1.

Arm type

Placebo

Investigational medicinal product name

Physiological Saline

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Doses were administered intramuscularly in the deltoid of the arm at Months 0 and 1

Number of subjects in period 1	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Started	7	6	24	25	40	40
Completed	6	5	22	25	40	40
Not completed	1	1	2	0	0	0
Consent withdrawn by subject	1	1	1	-	-	-
Lost to follow-up	-	-	1	-	-	-

Baseline characteristics

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Reporting group title

TB Treatment GSK 692342 Group

Reporting group description

Subjects having completed the intensive phase of treatment, i.e. 2 to 4 months post initiation of treatment, who received the GSK 692342 vaccine according to a 2-dose schedule at Months 0 and 1.

Reporting group title

TB Treatment Saline Group

Reporting group description

Reporting group title

TB Treated GSK 692342 Group

Reporting group description

Reporting group title

TB Treated Saline Group

Reporting group description

Reporting group title

TB Naive GSK 692342 Group

Reporting group description

Subjects unaffected by tuberculosis who received the GSK 692342 vaccine according to a 2-dose schedule at Months 0 and 1.

Reporting group title

TB Naive Saline Group

Reporting group description

Subjects unaffected by tuberculosis who received a placebo (physiological saline) according to a 2-dose schedule at Months 0 and 1.

Reporting group values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group	Total
Number of subjects	7	6	24	25	40	40	142
Age categorical
Units: Subjects
In utero							0
Preterm newborn infants (gestational age < 37 wks)							0
Newborns (0-27 days)							0
Infants and toddlers (28 days-23 months)							0
Children (2-11 years)							0
Adolescents (12-17 years)							0
Adults (18-64 years)							0
From 65-84 years							0
85 years and over							0
Age continuous
Units: years
arithmetic mean (standard deviation)	42.9 ( 11.5 )	44.7 ( 11.8 )	44.5 ( 10.3 )	47 ( 9.8 )	33.8 ( 8.5 )	33.3 ( 9.8 )	-
Gender categorical
Units: Subjects
Female	1	2	13	7	16	21	60
Male	6	4	11	18	24	19	82

End points

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Reporting group title

TB Treatment GSK 692342 Group

Reporting group description

Subjects having completed the intensive phase of treatment, i.e. 2 to 4 months post initiation of treatment, who received the GSK 692342 vaccine according to a 2-dose schedule at Months 0 and 1.

Reporting group title

TB Treatment Saline Group

Reporting group description

Reporting group title

TB Treated GSK 692342 Group

Reporting group description

Reporting group title

TB Treated Saline Group

Reporting group description

Reporting group title

TB Naive GSK 692342 Group

Reporting group description

Subjects unaffected by tuberculosis who received the GSK 692342 vaccine according to a 2-dose schedule at Months 0 and 1.

Reporting group title

TB Naive Saline Group

Reporting group description

Subjects unaffected by tuberculosis who received a placebo (physiological saline) according to a 2-dose schedule at Months 0 and 1.

Primary: Number of subjects with solicited local symptoms

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End point title

Number of subjects with solicited local symptoms ^[1]

End point description

End point type

Primary

End point timeframe

During the 7 day (Days 0-6), after each vaccine dose

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	7	6	24	25	40	40
Units: Subjects
Pain, D1 (N=7,6,24,25,40,40)	6	1	21	2	38	5
Redness, D1 (N=7,6,24,25,40,40)	2	0	4	0	7	0
Swelling, D1 (N=7,6,24,25,40,40)	2	0	5	1	4	0
Pain, D2 (N=6,5,21,25,39,39)	5	1	19	1	36	6
Redness, D2 (N=6,5,21,25,39,39)	3	0	7	0	6	0
Swelling, D2 (N=6,5,21,25,39,39)	3	0	4	0	11	0
Pain, Across (N=7,6,24,25,40,40)	6	1	22	3	39	8
Redness, Across (N=7,6,24,25,40,40)	3	0	8	0	10	0
Swelling, Across (N=7,6,24,25,40,40)	3	0	6	1	11	0

No statistical analyses for this end point

Primary: Number of subjects with solicited general symptoms

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End point title

Number of subjects with solicited general symptoms ^[2]

End point description

End point type

Primary

End point timeframe

During the 7 day (Days 0-6), after each vaccine dose

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	7	6	24	25	40	40
Units: Subjects
Fatigue, D1 (N=7,6,24,25,40,40)	1	2	14	6	19	8
Gastrointestinal symptoms, D1 (N=7,6,24,25,40,40)	0	0	4	2	5	5
Headache, D1 (N=7,6,24,25,40,40)	1	0	11	4	8	5
Malaise, D1 (N=7,6,24,25,40,40)	1	1	11	2	14	8
Myalgia, D1 (N=7,6,24,25,40,40)	2	0	13	4	24	7
Temperature/(Axillary), D1 (N=7,6,24,25,40,40)	0	0	1	0	2	0
Fatigue, D2 (N=6,5,21,25,39,39)	3	1	13	5	33	7
Gastrointestinal symptoms, D2 (N=6,5,21,25,39,39)	2	0	7	3	13	3
Headache, D2 (N=6,5,21,25,39,39)	3	1	12	2	22	3
Malaise, D2 (N=6,5,21,25,39,39)	3	2	11	5	32	3
Myalgia, D2 (N=6,5,21,25,39,39)	3	1	14	4	28	3
Temperature/(Axillary), D2 (N=6,5,21,25,39,39)	4	1	9	0	16	0
Fatigue, Across (N=7,6,24,25,40,40)	3	2	17	8	36	10
Gastrointestinal symptoms, Across (N=7,6,24,25,40,	2	0	10	4	16	6
Headache, Across (N=7,6,24,25,40,40)	3	1	18	4	24	6
Malaise, Across (N=7,6,24,25,40,40)	3	2	16	6	35	9
Myalgia, Across (N=7,6,24,25,40,40)	3	1	18	5	34	7
Temperature/(Axillary), Across (N=7,6,24,25,40,40)	4	1	10	0	17	0

No statistical analyses for this end point

Primary: Number of subjects with adverse events (AEs)

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End point title

Number of subjects with adverse events (AEs) ^[3]

End point description

End point type

Primary

End point timeframe

During the 30 day (Days 0-29) after vaccination

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	7	6	24	25	40	40
Units: Subjects
Any AEs	1	2	14	7	19	8

No statistical analyses for this end point

Primary: Number of subjects with serious adverse events (SAEs)

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End point title

Number of subjects with serious adverse events (SAEs) ^[4]

End point description

End point type

Primary

End point timeframe

Up to day 210

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed.

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	7	6	24	25	40	40
Units: Subjects
Any SAEs	0	0	2	2	1	0

No statistical analyses for this end point

Secondary: Number of subjects with anti-mycobacterium tuberculosis fusion protein M72 antibodies.

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End point title

Number of subjects with anti-mycobacterium tuberculosis fusion protein M72 antibodies.

End point description

Cut-off values assessed were greater than or equal to 2.8 measured by ELISA (Enzyme Linked Immunosorbent Assay) in the sera of subjects seronegative before vaccination.

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Day 30 – D30), post-dose 2 (Days 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	7	4	21	25	38	39
Units: Subjects
Anti-M72, PRE (N=7; 4; 21; 25; 37; 39)	0	0	0	0	1	2
Anti-M72, D30 (N=6; 4; 21; 25; 38; 39)	5	0	19	0	26	2
Anti-M72, D60 (N=6; 3; 19; 25; 38; 39)	6	0	18	0	37	3
Anti-M72, D210 (N=6; 3; 19; 25; 38; 39)	6	0	18	0	38	1

No statistical analyses for this end point

Secondary: Concentrations of mycobacterium tuberculosis fusion protein M72.

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End point title

Concentrations of mycobacterium tuberculosis fusion protein M72.

End point description

Concentrations are presented as geometric mean concentrations (GMCs), expressed in ELISA units per millilitre (EU/mL)

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Day 30 – D30), post-dose 2 (Days 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	7	4	21	25	38	39
Units: EU/mL
geometric mean (confidence interval 95%)
Anti-M72, PRE (N=7; 4; 21; 25; 37; 39)	1.4 (1.4 to 1.4)	1.4 (1.4 to 1.4)	1.4 (1.4 to 1.4)	1.4 (1.4 to 1.4)	1.4 (1.4 to 1.5)	1.5 (1.4 to 1.6)
Anti-M72, D30 (N=6; 4; 21; 25; 38; 39)	6.7 (2.1 to 21)	1.4 (1.4 to 1.4)	11.7 (6.3 to 22)	1.4 (1.4 to 1.4)	4.5 (3.3 to 6.2)	1.5 (1.4 to 1.6)
Anti-M72, D60 (N=6; 3; 19; 25; 38; 39)	206.6 (46.2 to 923.2)	1.4 (1.4 to 1.4)	226.2 (99 to 517.2)	1.4 (1.4 to 1.4)	248.6 (171 to 361.4)	1.7 (1.3 to 2.3)
Anti-M72, D210 (N=6; 3; 19; 25; 38; 39)	38.4 (18.9 to 77.9)	1.4 (1.4 to 1.4)	50.9 (27.3 to 94.8)	1.4 (1.4 to 1.4)	45.6 (34.2 to 60.8)	1.4 (1.4 to 1.5)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of the different immune markers.

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End point title

Frequency of M72-specific CD4+ T cells per million cells expressing any combination of the different immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD4-ALL doubles, PRE (N=4; 3; 15; 22; 30; 30)	247 (204.5 to 333.5)	178 (70 to 651)	347 (196 to 523)	549.5 (375 to 997)	286 (173 to 471)	352 (170 to 579)
CD4-ALL doubles, D7 (N=4; 3; 13; 15; 26; 28)	997.5 (714 to 1345)	182 (82 to 431)	1097 (985 to 1760)	469 (328 to 1075)	801.5 (440 to 1492)	265.5 (167.5 to 571.5)
CD4-ALL doubles, D30 (N=5; 2; 16; 16; 34; 34)	2959 (1289 to 2989)	730 (216 to 1244)	2616.5 (1417 to 5614)	466 (261.5 to 1145.5)	1228.5 (941 to 2131)	312.5 (202 to 726)
CD4-ALL doubles, D37 (N=5; 3; 18; 19; 34; 34)	4433 (3024 to 10010)	273 (221 to 445)	5705.5 (2219 to 11228)	533 (227 to 1235)	5987.5 (3987 to 9605)	247 (175 to 387)
CD4-ALL doubles, D60 (N=4; 2; 15; 18; 31; 32)	5648 (3686 to 7957)	241 (224 to 258)	2072 (1083 to 4199)	517 (352 to 1242)	5153 (2884 to 8978)	240 (146 to 476)
CD4-ALL doubles, D210 (N=6; 3; 13; 17; 37; 36)	2922.5 (967 to 4411)	118 (116 to 307)	1154 (1028 to 1808)	445 (243 to 734)	2155 (1389 to 4160)	254 (166 to 383)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing 2 or more immune markers among 6.

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End point title

Frequency of M72-specific CD4+ T cells per million cells expressing 2 or more immune markers among 6.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a), CD40-ligand (CD40-L), Interleukin-17 (IL-17) and/or Interleukin-17 (IL-17).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	16	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD4-At least 2, PRE (N=4; 3; 15; 22; 30; 30)	260 (217.5 to 346.5)	207 (96 to 687)	364 (238 to 536)	562.5 (402 to 1010)	325 (240 to 512)	365 (214 to 609)
CD4- At least 2, D7 (N=4; 3; 13; 15; 26; 28)	1010.5 (733.5 to 1358)	208 (95 to 457)	1152 (1011 to 1895)	482 (347 to 1088)	856 (479 to 1505)	278.5 (193.5 to 600)
CD4- At least 2, D30 (N=5; 2; 16; 16; 34; 34)	2972 (1302 to 3002)	765 (229 to 1301)	2636 (1437 to 5655)	497 (282 to 1179)	1248.5 (954 to 2144)	348.5 (238 to 754)
CD4- At least 2, D37 (N=5; 3; 18; 19; 34; 34)	4446 (3037 to 10107)	316 (234 to 458)	5733.5 (2232 to 11281)	565 (260 to 1262)	6051.5 (4191 to 9679)	277.5 (190 to 425)
CD4- At least 2, D60 (N=4; 2; 15; 18; 31; 32)	5661 (3699 to 7976.5)	254 (237 to 271)	2101 (1115 to 4275)	583 (378 to 1256)	5185 (2897 to 9031)	258 (160.5 to 496)
CD4- At least 2, D210 (N=6; 3; 13; 17; 37; 36)	2948.5 (993 to 4670)	131 (129 to 320)	1167 (1041 to 1821)	480 (298 to 770)	2269 (1419 to 4173)	299 (201.5 to 449.5)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

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End point title

Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD40L+/IL2+/TNFa+/IFNg+, PRE (N=4;3;15;22;30;30)	106.5 (68 to 134)	4 (4 to 252)	87 (34 to 140)	124 (74 to 186)	60 (4 to 108)	54 (17 to 142)
CD40L+/IL2+/TNFa+/IFNg+, D7 (N=4;3;13;15;26;28)	267.5 (218.5 to 493.5)	42 (4 to 241)	329 (140 to 454)	84 (25 to 154)	87 (24 to 229)	55.5 (4 to 132)
CD40L+/IL2+/TNFa+/IFNg+, D30 (N=5;2;16;16;34;34)	1066 (261 to 1233)	330.5 (33 to 628)	776 (341 to 1070.5)	71 (30.5 to 161.5)	89.5 (37 to 287)	47 (17 to 157)
CD40L+/IL2+/TNFa+/IFNg+, D37 (N=5;3;18;19;34;34)	1186 (1084 to 1403)	80 (44 to 158)	897.5 (333 to 1123)	87 (52 to 135)	436.5 (192 to 592)	45 (11 to 106)
CD40L+/IL2+/TNFa+/IFNg+, D60 (N=4;2;15;18;31;32)	1444 (1039 to 1615.5)	4 (4 to 4)	417 (87 to 815)	132 (73 to 171)	436 (219 to 826)	31 (4 to 130.5)
CD40L+/IL2+/TNFa+/IFNg+, D210 (N=6;3;13;17;37;36)	585.5 (288 to 997)	18 (4 to 74)	288 (217 to 313)	68 (38 to 157)	201 (95 to 504)	35.5 (18 to 89.5)
CD40L+/IL2+/TNFa+/IFNg-, PRE (N=4;3;15;22;30;30)	12 (4 to 22)	55 (4 to 93)	25 (4 to 48)	20.5 (4 to 58)	4 (4 to 26)	4 (4 to 33)
CD40L+/IL2+/TNFa+/IFNg-, D7 (N=4;3;13;15;26;28)	33 (17 to 44)	17 (4 to 45)	44 (31 to 116)	27 (4 to 34)	19 (4 to 54)	16.5 (4 to 34)
CD40L+/IL2+/TNFa+/IFNg-, D30 (N=5;2;16;16;34;34)	204 (162 to 213)	48 (4 to 92)	250 (149.5 to 370.5)	16 (4 to 43)	279.5 (144 to 385)	20.5 (4 to 50)
CD40L+/IL2+/TNFa+/IFNg-, D37 (N=5;3;18;19;34;34)	436 (246 to 550)	35 (31 to 49)	292 (154 to 525)	9 (4 to 43)	558.5 (250 to 884)	4.5 (4 to 37)
CD40L+/IL2+/TNFa+/IFNg-, D60 (N=4;2;15;18;31;32)	654 (561.5 to 1140.5)	28 (24 to 32)	301 (183 to 458)	19 (4 to 42)	1117 (551 to 1690)	20 (4 to 33)
CD40L+/IL2+/TNFa+/IFNg-, D210 (N=6;3;13;17;37;36)	448 (202 to 552)	4 (4 to 5)	148 (116 to 209)	18 (4 to 31)	566 (245 to 997)	4 (4 to 27.5)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

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End point title

Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD40L+/IL2+/TNFa-/IFNg+, PRE (N=4;3;15;22;30;30)	4 (4 to 11)	4 (4 to 26)	4 (4 to 23)	17 (4 to 31)	4 (4 to 27)	12.5 (4 to 34)
CD40L+/IL2+/TNFa-/IFNg+, D7 (N=4;3;13;15;26;28)	33 (12 to 50.5)	4 (4 to 47)	40 (31 to 103)	4 (4 to 19)	32.5 (4 to 84)	4 (4 to 27.5)
CD40L+/IL2+/TNFa-/IFNg+, D30 (N=5;2;16;16;34;34)	48 (47 to 117)	25.5 (4 to 47)	82.5 (39 to 116)	4 (4 to 18.5)	39.5 (25 to 76)	17 (4 to 37)
CD40L+/IL2+/TNFa-/IFNg+, D37 (N=5;3;18;19;34;34)	118 (89 to 307)	4 (4 to 19)	133.5 (42 to 242)	4 (4 to 20)	278 (161 to 525)	17 (4 to 47)
CD40L+/IL2+/TNFa-/IFNg+, D60 (N=4;2;15;18;31;32)	151.5 (129.5 to 246)	32 (4 to 60)	75 (44 to 236)	4 (4 to 18)	269 (128 to 500)	4 (4 to 28.5)
CD40L+/IL2+/TNFa-/IFNg+, D210 (N=6;3;13;17;37;36)	112.5 (31 to 218)	18 (4 to 60)	47 (24 to 95)	4 (4 to 29)	126 (61 to 296)	10.5 (4 to 40)
CD40L+/IL2+/TNFa-/IFNg-, PRE (N=4;3;15;22;30;30)	11.5 (4 to 41)	4 (4 to 17)	14 (4 to 22)	17.5 (4 to 45)	19.5 (4 to 37)	4 (4 to 24)
CD40L+/IL2+/TNFa-/IFNg-, D7 (N=4;3;13;15;26;28)	45.5 (4 to 88)	4 (4 to 17)	43 (17 to 75)	4 (4 to 46)	44.5 (4 to 69)	5 (4 to 49.5)
CD40L+/IL2+/TNFa-/IFNg-, D30 (N=5;2;16;16;34;34)	102 (32 to 201)	84.5 (33 to 136)	150.5 (69 to 253.5)	25 (4 to 53)	300 (202 to 519)	18 (4 to 49)
CD40L+/IL2+/TNFa-/IFNg-, D37 (N=5;3;18;19;34;34)	263 (94 to 305)	20 (4 to 65)	182 (67 to 393)	4 (4 to 29)	732 (498 to 946)	4 (4 to 16)
CD40L+/IL2+/TNFa-/IFNg-, D60 (N=4;2;15;18;31;32)	381.5 (223.5 to 561.5)	46.5 (32 to 61)	171 (84 to 514)	4 (4 to 38)	939 (534 to 1537)	17.5 (4 to 30)
CD40L+/IL2+/TNFa-/IFNg-, D210 (N=6;3;13;17;37;36)	166.5 (66 to 380)	18 (4 to 31)	126 (101 to 148)	17 (4 to 32)	453 (281 to 768)	11 (4 to 37)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Top of page

End point title

Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD40L+/IL2-/TNFa+/IFNg+, PRE (N=4;3;15;22;30;30)	67 (47 to 74.5)	55 (4 to 161)	61 (19 to 218)	188.5 (66 to 272)	48.5 (17 to 101)	44.5 (19 to 164)
CD40L+/IL2-/TNFa+/IFNg+, D7 (N=4;3;13;15;26;28)	270.5 (224 to 408.5)	4 (4 to 73)	389 (207 to 735)	151 (79 to 278)	232 (46 to 491)	43 (10.5 to 148.5)
CD40L+/IL2-/TNFa+/IFNg+, D30 (N=5;2;16;16;34;34)	563 (541 to 1023)	115 (4 to 226)	902 (397.5 to 2177)	132.5 (54.5 to 398)	156.5 (76 to 481)	71.5 (18 to 221)
CD40L+/IL2-/TNFa+/IFNg+, D37 (N=5;3;18;19;34;34)	1236 (886 to 3361)	4 (4 to 111)	1828 (462 to 3273)	253 (45 to 463)	738.5 (422 to 1663)	46.5 (17 to 114)
CD40L+/IL2-/TNFa+/IFNg+, D60 (N=4;2;15;18;31;32)	2219.5 (1183 to 3234)	24.5 (4 to 45)	608 (361 to 1433)	149.5 (97 to 340)	560 (192 to 1563)	55.5 (25.5 to 150)
CD40L+/IL2-/TNFa+/IFNg+, D210 (N=6;3;13;17;37;36)	869 (202 to 1422)	32 (4 to 33)	439 (218 to 620)	174 (46 to 248)	301 (137 to 602)	22 (4 to 137)
CD40L+/IL2-/TNFa+/IFNg-, PRE (N=4;3;15;22;30;30)	10 (4 to 20.5)	20 (4 to 73)	8 (4 to 38)	18 (4 to 43)	9.5 (4 to 47)	20 (4 to 52)
CD40L+/IL2-/TNFa+/IFNg-, D7 (N=4;3;13;15;26;28)	34 (18 to 40.5)	17 (4 to 47)	58 (24 to 74)	4 (4 to 31)	40.5 (17 to 98)	4 (4 to 41)
CD40L+/IL2-/TNFa+/IFNg-, D30 (N=5;2;16;16;34;34)	132 (45 to 150)	25.5 (4 to 47)	152.5 (79 to 215)	25.5 (4 to 52.5)	125.5 (71 to 216)	17 (4 to 28)
CD40L+/IL2-/TNFa+/IFNg-, D37 (N=5;3;18;19;34;34)	276 (117 to 889)	37 (4 to 87)	375.5 (230 to 805)	40 (4 to 84)	915 (471 to 1575)	18 (4 to 38)
CD40L+/IL2-/TNFa+/IFNg-, D60 (N=4;2;15;18;31;32)	359.5 (255 to 556.5)	62.5 (4 to 121)	176 (75 to 327)	26 (4 to 65)	792 (421 to 1060)	4 (4 to 38.5)
CD40L+/IL2-/TNFa+/IFNg-, D210 (N=6;3;13;17;37;36)	167 (75 to 191)	19 (4 to 35)	77 (23 to 134)	4 (4 to 40)	272 (142 to 358)	18 (4 to 34.5)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Top of page

End point title

Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD40L+/IL2-/TNFa-/IFNg+, PRE (N=4;3;15;22;30;30)	10.5 (4 to 40)	17 (4 to 20)	25 (6 to 61)	43 (4 to 80)	27.5 (4 to 54)	12 (4 to 60)
CD40L+/IL2-/TNFa-/IFNg+, D7 (N=4;3;13;15;26;28)	113.5 (62.5 to 155.5)	4 (4 to 31)	227 (65 to 469)	22 (4 to 71)	163 (100 to 239)	29.5 (4 to 54)
CD40L+/IL2-/TNFa-/IFNg+, D30 (N=5;2;16;16;34;34)	71 (60 to 75)	41 (32 to 50)	124.5 (64.5 to 284)	13.5 (4 to 65)	86.5 (27 to 154)	30 (4 to 59)
CD40L+/IL2-/TNFa-/IFNg+, D37 (N=5;3;18;19;34;34)	406 (406 to 1923)	5 (4 to 31)	649 (245 to 1982)	17 (4 to 72)	1355.5 (917 to 2882)	19 (4 to 58)
CD40L+/IL2-/TNFa-/IFNg+, D60 (N=4;2;15;18;31;32)	213 (75 to 378.5)	17.5 (4 to 31)	147 (58 to 339)	20.5 (4 to 46)	399 (135 to 664)	4 (4 to 35.5)
CD40L+/IL2-/TNFa-/IFNg+, D210 (N=6;3;13;17;37;36)	129 (18 to 304)	4 (4 to 73)	57 (37 to 115)	32 (4 to 62)	107 (65 to 180)	30.5 (5 to 48)
CD40L+/IL2-/TNFa-/IFNg-, PRE (N=4;3;15;22;30;30)	4 (4 to 98.5)	103 (4 to 244)	19 (4 to 41)	10.5 (4 to 73)	4 (4 to 29)	4 (4 to 32)
CD40L+/IL2-/TNFa-/IFNg-, D7 (N=4;3;13;15;26;28)	4 (4 to 10.5)	4 (4 to 506)	14 (4 to 83)	4 (4 to 23)	19 (4 to 171)	4 (4 to 41.5)
CD40L+/IL2-/TNFa-/IFNg-, D30 (N=5;2;16;16;34;34)	4 (4 to 18)	1375.5 (4 to 2747)	208 (11 to 689)	4 (4 to 37)	342 (133 to 769)	4 (4 to 136)
CD40L+/IL2-/TNFa-/IFNg-, D37 (N=5;3;18;19;34;34)	973 (17 to 1644)	213 (20 to 373)	1544 (787 to 2630)	18 (4 to 200)	3575.5 (2450 to 6212)	4 (4 to 32)
CD40L+/IL2-/TNFa-/IFNg-, D60 (N=4;2;15;18;31;32)	4 (4 to 373.5)	4 (4 to 4)	168 (4 to 727)	4 (4 to 104)	1426 (653 to 2820)	4 (4 to 89)
CD40L+/IL2-/TNFa-/IFNg-, D210 (N=6;3;13;17;37;36)	10.5 (4 to 712)	4 (4 to 4)	296 (13 to 743)	45 (4 to 233)	497 (34 to 900)	4 (4 to 89.5)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Top of page

End point title

Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD40L-/IL2+/TNFa+/IFNg+, PRE (N=4;3;15;22;30;30)	4 (4 to 4)	4 (4 to 26)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg+, D7 (N=4;3;13;15;26;28)	4 (4 to 68)	4 (4 to 17)	19 (4 to 74)	4 (4 to 18)	4 (4 to 26)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg+, D30 (N=5;2;16;16;34;34)	4 (4 to 41)	26 (4 to 48)	35 (4 to 85)	4 (4 to 10.5)	4 (4 to 25)	4 (4 to 19)
CD40L-/IL2+/TNFa+/IFNg+, D37 (N=5;3;18;19;34;34)	89 (46 to 93)	4 (4 to 4)	64.5 (17 to 148)	4 (4 to 4)	32.5 (4 to 66)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg+, D60 (N=4;2;15;18;31;32)	39.5 (17.5 to 62.5)	4 (4 to 4)	4 (4 to 60)	4 (4 to 4)	19 (4 to 33)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg+, D210 (N=6;3;13;17;37;36)	19 (4 to 32)	4 (4 to 4)	4 (4 to 19)	4 (4 to 4)	4 (4 to 31)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg-, PRE (N=4;3;15;22;30;30)	4 (4 to 11)	4 (4 to 4)	4 (4 to 20)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg-, D7 (N=4;3;13;15;26;28)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg-, D30 (N=5;2;16;16;34;34)	17 (4 to 17)	4 (4 to 4)	19.5 (4 to 54.5)	4 (4 to 17.5)	17.5 (4 to 33)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg-, D37 (N=5;3;18;19;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 24)	4 (4 to 4)	34 (8 to 67)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg-, D60 (N=4;2;15;18;31;32)	21 (10.5 to 55.5)	4 (4 to 4)	4 (4 to 19)	4 (4 to 4)	45 (16 to 79)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg-, D210 (N=6;3;13;17;37;36)	4 (4 to 21)	17 (4 to 18)	4 (4 to 4)	4 (4 to 4)	4 (4 to 34)	4 (4 to 10.5)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Top of page

End point title

Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD40L-/IL2+/TNFa-/IFNg+, PRE (N=4;3;15;22;30;30)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa-/IFNg+, D7 (N=4;3;13;15;26;28)	4 (4 to 16.5)	4 (4 to 4)	17 (4 to 18)	4 (4 to 4)	4 (4 to 19)	4 (4 to 4)
CD40L-/IL2+/TNFa-/IFNg+, D30 (N=5;2;16;16;34;34)	4 (4 to 4)	4 (4 to 4)	11 (4 to 23.5)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa-/IFNg+, D37 (N=5;3;18;19;34;34)	17 (17 to 32)	4 (4 to 4)	17 (4 to 24)	4 (4 to 4)	19.5 (4 to 61)	4 (4 to 4)
CD40L-/IL2+/TNFa-/IFNg+, D60 (N=4;2;15;18;31;32)	4 (4 to 4)	4 (4 to 4)	4 (4 to 20)	4 (4 to 4)	4 (4 to 22)	4 (4 to 4)
CD40L-/IL2+/TNFa-/IFNg+, D210 (N=6;3;13;17;37;36)	4 (4 to 24)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa-/IFNg-, PRE (N=4;3;15;22;30;30)	4 (4 to 10.5)	4 (4 to 20)	4 (4 to 23)	4 (4 to 18)	4 (4 to 4)	4 (4 to 21)
CD40L-/IL2+/TNFa-/IFNg-, D7 (N=4;3;13;15;26;28)	4 (4 to 18)	4 (4 to 17)	4 (4 to 17)	17 (4 to 30)	18.5 (4 to 26)	4 (4 to 12)
CD40L-/IL2+/TNFa-/IFNg-, D30 (N=5;2;16;16;34;34)	30 (19 to 32)	4 (4 to 4)	21 (6.5 to 44.5)	4 (4 to 19)	18 (4 to 32)	4 (4 to 20)
CD40L-/IL2+/TNFa-/IFNg-, D37 (N=5;3;18;19;34;34)	4 (4 to 4)	4 (4 to 4)	27.5 (17 to 45)	4 (4 to 5)	40.5 (19 to 82)	4 (4 to 20)
CD40L-/IL2+/TNFa-/IFNg-, D60 (N=4;2;15;18;31;32)	11 (4.5 to 28.5)	17.5 (4 to 31)	4 (4 to 20)	11 (4 to 23)	49 (20 to 70)	4 (4 to 18)
CD40L-/IL2+/TNFa-/IFNg-, D210 (N=6;3;13;17;37;36)	17.5 (4 to 59)	4 (4 to 32)	4 (4 to 17)	4 (4 to 26)	25 (8 to 44)	4 (4 to 19.5)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Top of page

End point title

Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD40L-/IL2-/TNFa+/IFNg+, PRE (N=4;3;15;22;30;30)	10.5 (4 to 25)	4 (4 to 4)	24 (4 to 59)	13.5 (4 to 136)	17.5 (4 to 32)	4 (4 to 57)
CD40L-/IL2-/TNFa+/IFNg+, D7 (N=4;3;13;15;26;28)	53.5 (34.5 to 87.5)	4 (4 to 17)	102 (40 to 230)	18 (4 to 234)	53 (17 to 246)	4 (4 to 53)
CD40L-/IL2-/TNFa+/IFNg+, D30 (N=5;2;16;16;34;34)	76 (4 to 117)	26 (4 to 48)	112 (21.5 to 212)	44 (10.5 to 334.5)	42 (4 to 89)	20 (4 to 46)
CD40L-/IL2-/TNFa+/IFNg+, D37 (N=5;3;18;19;34;34)	246 (116 to 288)	34 (4 to 65)	212.5 (94 to 698)	50 (5 to 361)	185.5 (61 to 463)	4 (4 to 33)
CD40L-/IL2-/TNFa+/IFNg+, D60 (N=4;2;15;18;31;32)	162.5 (76 to 214)	14 (4 to 24)	34 (19 to 338)	46 (4 to 534)	69 (32 to 277)	18.5 (4 to 45.5)
CD40L-/IL2-/TNFa+/IFNg+, D210 (N=6;3;13;17;37;36)	19.5 (4 to 156)	4 (4 to 18)	30 (18 to 112)	29 (4 to 169)	46 (4 to 77)	11.5 (4 to 38)
CD40L-/IL2-/TNFa+/IFNg-, PRE (N=4;3;15;22;30;30)	11.5 (5 to 31)	18 (18 to 29)	20 (4 to 55)	4 (4 to 41)	8 (4 to 38)	22.5 (4 to 68)
CD40L-/IL2-/TNFa+/IFNg-, D7 (N=4;3;13;15;26;28)	25.5 (11 to 38)	17 (4 to 45)	19 (4 to 75)	17 (4 to 32)	26 (4 to 57)	28.5 (4 to 81.5)
CD40L-/IL2-/TNFa+/IFNg-, D30 (N=5;2;16;16;34;34)	21 (6 to 26)	4 (4 to 4)	51.5 (15 to 101)	32.5 (4.5 to 67)	8 (4 to 61)	12.5 (4 to 31)
CD40L-/IL2-/TNFa+/IFNg-, D37 (N=5;3;18;19;34;34)	46 (31 to 153)	66 (31 to 117)	87 (31 to 256)	11 (4 to 119)	309 (137 to 532)	7.5 (4 to 26)
CD40L-/IL2-/TNFa+/IFNg-, D60 (N=4;2;15;18;31;32)	67 (57.5 to 108)	50 (40 to 60)	23 (4 to 104)	36 (4 to 59)	88 (35 to 225)	22 (4 to 44)
CD40L-/IL2-/TNFa+/IFNg-, D210 (N=6;3;13;17;37;36)	4 (4 to 60)	4 (4 to 4)	5 (4 to 57)	23 (4 to 54)	24 (4 to 76)	4 (4 to 34.5)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Top of page

End point title

Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD40L-/IL2-/TNFa-/IFNg+, PRE (N=4;3;15;22;30;30)	17.5 (4 to 52.5)	20 (4 to 61)	47 (4 to 64)	51 (4 to 99)	70 (38 to 157)	14.5 (4 to 85)
CD40L-/IL2-/TNFa-/IFNg+, D7 (N=4;3;13;15;26;28)	69.5 (17.5 to 114)	4 (4 to 83)	59 (12 to 363)	46 (6 to 482)	78 (32 to 248)	25.5 (4 to 76)
CD40L-/IL2-/TNFa-/IFNg+, D30 (N=5;2;16;16;34;34)	45 (45 to 61)	4 (4 to 4)	52 (4 to 201.5)	33.5 (4 to 270)	47 (4 to 138)	26.5 (4 to 132)
CD40L-/IL2-/TNFa-/IFNg+, D37 (N=5;3;18;19;34;34)	191 (89 to 408)	34 (31 to 97)	273 (131 to 720)	27 (4 to 261)	495.5 (267 to 1466)	19 (4 to 86)
CD40L-/IL2-/TNFa-/IFNg+, D60 (N=4;2;15;18;31;32)	14.5 (4 to 48.5)	4 (4 to 4)	32 (4 to 267)	51.5 (17 to 144)	129 (40 to 276)	19.5 (4 to 84)
CD40L-/IL2-/TNFa-/IFNg+, D210 (N=6;3;13;17;37;36)	53.5 (31 to 117)	4 (4 to 60)	30 (4 to 85)	34 (4 to 92)	31 (4 to 126)	55 (32.5 to 115)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing at least 2 immune markers.

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End point title

Frequency of M72-specific CD8+ T cells per million cells expressing at least 2 immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD8-ALL doubles, PRE (N=4; 3; 15; 22; 30; 30)	93 (63.5 to 269)	44 (44 to 135)	99 (75 to 159)	110.5 (59 to 326)	73 (44 to 144)	69.5 (44 to 132)
CD8-ALL doubles, D7 (N=4; 3; 13; 15; 26; 28)	94.5 (80.5 to 141)	72 (45 to 77)	222 (146 to 329)	62 (44 to 324)	74.5 (44 to 144)	92.5 (53 to 191)
CD8-ALL doubles, D30 (N=5; 2; 16; 16; 34; 34)	44 (44 to 64)	81.5 (44 to 119)	243 (101 to 385)	153.5 (75.5 to 1064)	80 (44 to 150)	77.5 (59 to 172)
CD8-ALL doubles, D37 (N=5; 3; 18; 19; 34; 34)	126 (118 to 134)	76 (44 to 93)	347 (97 to 604)	108 (59 to 295)	72.5 (57 to 149)	75.5 (44 to 140)
CD8-ALL doubles, D60 (N=4; 2; 15; 18; 31; 32)	85.5 (55.5 to 233)	118 (69 to 167)	189 (60 to 367)	161 (84 to 491)	96 (44 to 245)	71 (44 to 157.5)
CD8-ALL doubles, D210 (N=6; 3; 13; 17; 37; 36)	347.5 (170 to 572)	78 (44 to 91)	259 (61 to 312)	119 (44 to 390)	110 (69 to 248)	71.5 (49.5 to 233)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing 2 or more immune markers among 6.

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End point title

Frequency of M72-specific CD8+ T cells per million cells expressing 2 or more immune markers among 6.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a), CD40-ligand (CD40-L), Interleukin-17 (IL-17) and/or Interleukin-17 (IL-17).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD8-At least 2, PRE (N=4; 3; 15; 22; 30; 30)	106 (76.5 to 282)	57 (57 to 148)	143 (88 to 172)	151.5 (81 to 339)	96 (57 to 157)	85.5 (57 to 169)
CD8- At least 2, D7 (N=4; 3; 13; 15; 26; 28)	107.5 (93.5 to 154)	85 (58 to 90)	245 (159 to 369)	75 (57 to 337)	116 (71 to 158)	124 (88 to 232)
CD8- At least 2, D30 (N=5; 2; 16; 16; 34; 34)	57 (57 to 77)	109 (86 to 132)	256 (114 to 410.5)	166.5 (88.5 to 1077)	96 (73 to 163)	106.5 (77 to 198)
CD8- At least 2, D37 (N=5; 3; 18; 19; 34; 34)	139 (131 to 147)	89 (57 to 106)	362 (110 to 617)	121 (72 to 308)	85.5 (70 to 162)	103.5 (58 to 161)
CD8- At least 2, D60 (N=4; 2; 15; 18; 31; 32)	98.5 (68.5 to 246)	131 (82 to 180)	202 (89 to 380)	174 (97 to 504)	111 (76 to 270)	106.5 (57 to 191)
CD8- At least 2, D210 (N=6; 3; 13; 17; 37; 36)	403.5 (183 to 585)	91 (57 to 151)	272 (74 to 379)	133 (76 to 403)	137 (83 to 291)	124.5 (81.5 to 292)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Top of page

End point title

Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD40L+/IL2+/TNFa+/IFNg+, PRE (N=4;3;15;22;30;30)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa+/IFNg+, D7 (N=4;3;13;15;26;28)	4 (4 to 14)	4 (4 to 4)	4 (4 to 62)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa+/IFNg+, D30 (N=5;2;16;16;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 25)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa+/IFNg+, D37 (N=5;3;18;19;34;34)	4 (4 to 41)	4 (4 to 4)	4 (4 to 48)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa+/IFNg+, D60 (N=4;2;15;18;31;32)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa+/IFNg+, D210 (N=6;3;13;17;37;36)	58 (4 to 99)	4 (4 to 38)	4 (4 to 4)	4 (4 to 33)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa+/IFNg-, PRE (N=4;3;15;22;30;30)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa+/IFNg-, D7 (N=4;3;13;15;26;28)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa+/IFNg-, D30 (N=5;2;16;16;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa+/IFNg-, D37 (N=5;3;18;19;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa+/IFNg-, D60 (N=4;2;15;18;31;32)	4 (4 to 19)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa+/IFNg-, D210 (N=6;3;13;17;37;36)	35 (4 to 46)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 25)	4 (4 to 4)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Top of page

End point title

Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD40L+/IL2+/TNFa-/IFNg+, PRE (N=4;3;15;22;30;30)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa-/IFNg+, D7 (N=4;3;13;15;26;28)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa-/IFNg+, D30 (N=5;2;16;16;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa-/IFNg+, D37 (N=5;3;18;19;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa-/IFNg+, D60 (N=4;2;15;18;31;32)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa-/IFNg+, D210 (N=6;3;13;17;37;36)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa-/IFNg-, PRE (N=4;3;15;22;30;30)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa-/IFNg-, D7 (N=4;3;13;15;26;28)	4 (4 to 4)	4 (4 to 32)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa-/IFNg-, D30 (N=5;2;16;16;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa-/IFNg-, D37 (N=5;3;18;19;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa-/IFNg-, D60 (N=4;2;15;18;31;32)	4 (4 to 4)	14 (4 to 24)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2+/TNFa-/IFNg-, D210 (N=6;3;13;17;37;36)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Top of page

End point title

Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD40L+/IL2-/TNFa+/IFNg+, PRE (N=4;3;15;22;30;30)	4 (4 to 33.5)	4 (4 to 4)	4 (4 to 4)	4 (4 to 23)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2-/TNFa+/IFNg+, D7 (N=4;3;13;15;26;28)	4 (4 to 4)	4 (4 to 4)	4 (4 to 55)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2-/TNFa+/IFNg+, D30 (N=5;2;16;16;34;34)	4 (4 to 4)	4 (4 to 4)	36.5 (4 to 84)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2-/TNFa+/IFNg+, D37 (N=5;3;18;19;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 168)	4 (4 to 21)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2-/TNFa+/IFNg+, D60 (N=4;2;15;18;31;32)	4 (4 to 4)	4 (4 to 4)	4 (4 to 42)	4 (4 to 24)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2-/TNFa+/IFNg+, D210 (N=6;3;13;17;37;36)	4 (4 to 13)	4 (4 to 51)	4 (4 to 56)	4 (4 to 4)	4 (4 to 21)	4 (4 to 4)
CD40L+/IL2-/TNFa+/IFNg-, PRE (N=4;3;15;22;30;30)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2-/TNFa+/IFNg-, D7 (N=4;3;13;15;26;28)	4 (4 to 4)	4 (4 to 37)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2-/TNFa+/IFNg-, D30 (N=5;2;16;16;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 17)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2-/TNFa+/IFNg-, D37 (N=5;3;18;19;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2-/TNFa+/IFNg-, D60 (N=4;2;15;18;31;32)	4 (4 to 21)	24.5 (4 to 45)	4 (4 to 20)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L+/IL2-/TNFa+/IFNg-, D210 (N=6;3;13;17;37;36)	4 (4 to 4)	4 (4 to 4)	4 (4 to 21)	4 (4 to 4)	4 (4 to 19)	4 (4 to 9)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Top of page

End point title

Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD40L+/IL2-/TNFa-/IFNg+, PRE (N=4;3;15;22;30;30)	4 (4 to 23.5)	4 (4 to 26)	4 (4 to 5)	4 (4 to 4)	4 (4 to 26)	4 (4 to 18)
CD40L+/IL2-/TNFa-/IFNg+, D7 (N=4;3;13;15;26;28)	4 (4 to 4)	4 (4 to 4)	4 (4 to 54)	4 (4 to 22)	4 (4 to 24)	4 (4 to 4.5)
CD40L+/IL2-/TNFa-/IFNg+, D30 (N=5;2;16;16;34;34)	4 (4 to 4)	41.5 (4 to 79)	4 (4 to 4)	4 (4 to 28.5)	4 (4 to 25)	4 (4 to 31)
CD40L+/IL2-/TNFa-/IFNg+, D37 (N=5;3;18;19;34;34)	4 (4 to 4)	4 (4 to 36)	4 (4 to 4)	4 (4 to 4)	4 (4 to 21)	4 (4 to 23)
CD40L+/IL2-/TNFa-/IFNg+, D60 (N=4;2;15;18;31;32)	4 (4 to 21)	16.5 (4 to 29)	4 (4 to 4)	14.5 (4 to 46)	4 (4 to 76)	4 (4 to 14.5)
CD40L+/IL2-/TNFa-/IFNg+, D210 (N=6;3;13;17;37;36)	19.5 (4 to 88)	4 (4 to 4)	4 (4 to 35)	4 (4 to 4)	4 (4 to 29)	4 (4 to 34.5)
CD40L+/IL2-/TNFa-/IFNg-, PRE (N=4;3;15;22;30;30)	97.5 (4 to 412)	143 (4 to 178)	29 (4 to 203)	4 (4 to 139)	7.5 (4 to 130)	25 (4 to 222)
CD40L+/IL2-/TNFa-/IFNg-, D7 (N=4;3;13;15;26;28)	33.5 (4 to 68)	110 (93 to 390)	4 (4 to 4)	4 (4 to 413)	4 (4 to 183)	26 (4 to 164)
CD40L+/IL2-/TNFa-/IFNg-, D30 (N=5;2;16;16;34;34)	73 (4 to 113)	161 (83 to 239)	4 (4 to 23)	4 (4 to 78.5)	4 (4 to 71)	99.5 (4 to 288)
CD40L+/IL2-/TNFa-/IFNg-, D37 (N=5;3;18;19;34;34)	4 (4 to 203)	4 (4 to 216)	4 (4 to 293)	43 (4 to 125)	4 (4 to 127)	13.5 (4 to 213)
CD40L+/IL2-/TNFa-/IFNg-, D60 (N=4;2;15;18;31;32)	18.5 (4 to 163.5)	44.5 (4 to 85)	101 (4 to 345)	85 (4 to 270)	61 (4 to 153)	36.5 (4 to 214)
CD40L+/IL2-/TNFa-/IFNg-, D210 (N=6;3;13;17;37;36)	53 (15 to 92)	122 (4 to 202)	333 (4 to 583)	121 (4 to 249)	22 (4 to 311)	33.5 (4 to 302.5)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Top of page

End point title

Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD40L-/IL2+/TNFa+/IFNg+, PRE (N=4;3;15;22;30;30)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg+, D7 (N=4;3;13;15;26;28)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg+, D30 (N=5;2;16;16;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg+, D37 (N=5;3;18;19;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg+, D60 (N=4;2;15;18;31;32)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg+, D210 (N=6;3;13;17;37;36)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg-, PRE (N=4;3;15;22;30;30)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg-, D7 (N=4;3;13;15;26;28)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg-, D30 (N=5;2;16;16;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg-, D37 (N=5;3;18;19;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg-, D60 (N=4;2;15;18;31;32)	4 (4 to 15.5)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa+/IFNg-, D210 (N=6;3;13;17;37;36)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Top of page

End point title

Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD40L-/IL2+/TNFa-/IFNg+, PRE (N=4;3;15;22;30;30)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa-/IFNg+, D7 (N=4;3;13;15;26;28)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa-/IFNg+, D30 (N=5;2;16;16;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa-/IFNg+, D37 (N=5;3;18;19;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa-/IFNg+, D60 (N=4;2;15;18;31;32)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa-/IFNg+, D210 (N=6;3;13;17;37;36)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)
CD40L-/IL2+/TNFa-/IFNg-, PRE (N=4;3;15;22;30;30)	4 (4 to 4)	4 (4 to 4)	4 (4 to 41)	4 (4 to 4)	4 (4 to 4)	4 (4 to 5)
CD40L-/IL2+/TNFa-/IFNg-, D7 (N=4;3;13;15;26;28)	4 (4 to 4)	4 (4 to 37)	4 (4 to 4)	4 (4 to 4)	4 (4 to 20)	4 (4 to 23.5)
CD40L-/IL2+/TNFa-/IFNg-, D30 (N=5;2;16;16;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 32)	4 (4 to 4)	4 (4 to 19)	4 (4 to 4)
CD40L-/IL2+/TNFa-/IFNg-, D37 (N=5;3;18;19;34;34)	28 (4 to 49)	4 (4 to 4)	4 (4 to 6)	4 (4 to 4)	4 (4 to 18)	4 (4 to 28)
CD40L-/IL2+/TNFa-/IFNg-, D60 (N=4;2;15;18;31;32)	4 (4 to 15.5)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 20)	4 (4 to 19)
CD40L-/IL2+/TNFa-/IFNg-, D210 (N=6;3;13;17;37;36)	4 (4 to 13)	38 (4 to 98)	4 (4 to 4)	4 (4 to 4)	4 (4 to 4)	4 (4 to 19)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

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End point title

Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD40L-/IL2-/TNFa+/IFNg+, PRE (N=4;3;15;22;30;30)	4 (4 to 199.5)	4 (4 to 73)	4 (4 to 47)	30 (4 to 286)	4 (4 to 37)	4 (4 to 45)
CD40L-/IL2-/TNFa+/IFNg+, D7 (N=4;3;13;15;26;28)	50 (30.5 to 101)	4 (4 to 5)	32 (4 to 109)	4 (4 to 284)	4 (4 to 104)	9 (4 to 102)
CD40L-/IL2-/TNFa+/IFNg+, D30 (N=5;2;16;16;34;34)	4 (4 to 4)	4 (4 to 4)	4 (4 to 107)	91.5 (4 to 1024)	4 (4 to 39)	4 (4 to 73)
CD40L-/IL2-/TNFa+/IFNg+, D37 (N=5;3;18;19;34;34)	41 (4 to 66)	4 (4 to 53)	28.5 (4 to 285)	28 (4 to 228)	4 (4 to 30)	4 (4 to 85)
CD40L-/IL2-/TNFa+/IFNg+, D60 (N=4;2;15;18;31;32)	19 (4 to 144)	35 (4 to 66)	29 (4 to 149)	58 (4 to 432)	4 (4 to 39)	4 (4 to 45)
CD40L-/IL2-/TNFa+/IFNg+, D210 (N=6;3;13;17;37;36)	51 (4 to 264)	4 (4 to 4)	4 (4 to 184)	4 (4 to 101)	4 (4 to 27)	4 (4 to 30.5)
CD40L-/IL2-/TNFa+/IFNg-, PRE (N=4;3;15;22;30;30)	21 (4 to 80)	4 (4 to 61)	4 (4 to 36)	7.5 (4 to 37)	25.5 (4 to 57)	4 (4 to 18)
CD40L-/IL2-/TNFa+/IFNg-, D7 (N=4;3;13;15;26;28)	17 (4 to 61)	4 (4 to 5)	4 (4 to 59)	4 (4 to 82)	20.5 (4 to 39)	4 (4 to 27)
CD40L-/IL2-/TNFa+/IFNg-, D30 (N=5;2;16;16;34;34)	4 (4 to 4)	80 (4 to 156)	4 (4 to 67.5)	47.5 (6 to 123)	20.5 (4 to 67)	24.5 (4 to 71)
CD40L-/IL2-/TNFa+/IFNg-, D37 (N=5;3;18;19;34;34)	40 (4 to 128)	4 (4 to 69)	36.5 (4 to 112)	4 (4 to 43)	4 (4 to 27)	5 (4 to 64)
CD40L-/IL2-/TNFa+/IFNg-, D60 (N=4;2;15;18;31;32)	16 (4 to 54)	4 (4 to 4)	4 (4 to 89)	18.5 (4 to 90)	20 (4 to 56)	4.5 (4 to 30)
CD40L-/IL2-/TNFa+/IFNg-, D210 (N=6;3;13;17;37;36)	4 (4 to 4)	4 (4 to 8)	4 (4 to 4)	4 (4 to 42)	4 (4 to 60)	4 (4 to 29)

No statistical analyses for this end point

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

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End point title

Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

End point description

Immune markers expressed were among Interleukin-2 (IL-2), Interferon-gamma (IFN-g), Tumour necrosis factor-alpha (TNF-a) and/or CD40-ligand (CD40-L).

End point type

Secondary

End point timeframe

Prior to dose 1 (Day 0 - PRE), post-dose 1 (Days 7 – D7 and 30 – D30), post-dose 2 (Days 37 – D37, 60 – D60 and 210 – D210)

End point values	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Number of subjects analysed	6	3	18	22	37	36
Units: T cells/million cells
median (inter-quartile range (Q1-Q3))
CD40L-/IL2-/TNFa-/IFNg+, PRE (N=4;3;15;22;30;30)	54.5 (25.5 to 821)	6 (4 to 95)	70 (12 to 541)	216.5 (57 to 1831)	54.5 (4 to 159)	78.5 (25 to 349)
CD40L-/IL2-/TNFa-/IFNg+, D7 (N=4;3;13;15;26;28)	89 (36.5 to 893.5)	9 (4 to 31)	152 (4 to 575)	205 (90 to 1660)	69.5 (43 to 830)	90.5 (4.5 to 484.5)
CD40L-/IL2-/TNFa-/IFNg+, D30 (N=5;2;16;16;34;34)	96 (26 to 163)	118 (4 to 232)	127.5 (13 to 327.5)	386.5 (27 to 1969.5)	64.5 (4 to 438)	151.5 (28 to 467)
CD40L-/IL2-/TNFa-/IFNg+, D37 (N=5;3;18;19;34;34)	48 (4 to 78)	33 (4 to 81)	100.5 (48 to 326)	229 (4 to 1022)	46.5 (4 to 179)	83.5 (4 to 335)
CD40L-/IL2-/TNFa-/IFNg+, D60 (N=4;2;15;18;31;32)	147.5 (55 to 824.5)	4 (4 to 4)	70 (4 to 1116)	172 (18 to 1492)	13 (4 to 65)	59 (4 to 310)
CD40L-/IL2-/TNFa-/IFNg+, D210 (N=6;3;13;17;37;36)	286.5 (48 to 469)	4 (4 to 59)	51 (4 to 245)	85 (4 to 628)	69 (4 to 233)	60 (22 to 232.5)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Solicited symptoms: During the 7 day (Days 0-6), after each vaccine dose, unsolicited AEs: During the 30 day (Days 0-29) after vaccination, SAEs: Up to day 210

Adverse event reporting additional description

Results presented per group consist of a summary of the events (SAEs and AEs other than SAEs, respectively) reported, compiling overall number of subjects with events across the different periods of assessment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

18.0

Reporting group title

TB Treatment GSK 692342 Group

Reporting group description

Subjects having completed the intensive phase of treatment, i.e. 2 to 4 months post initiation of treatment, who received the GSK 692342 vaccine according to a 2-dose schedule at Months 0 and 1.

Reporting group title

TB Treatment Saline Group

Reporting group description

Reporting group title

TB Treated GSK 692342 Group

Reporting group description

Reporting group title

TB Treated Saline Group

Reporting group description

Reporting group title

TB Naive GSK 692342 Group

Reporting group description

Subjects unaffected by tuberculosis who received the GSK 692342 vaccine according to a 2-dose schedule at Months 0 and 1.

Reporting group title

TB Naive Saline Group

Reporting group description

Subjects unaffected by tuberculosis who received a placebo (physiological saline) according to a 2-dose schedule at Months 0 and 1.

Serious adverse events	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 7 (0.00%)	0 / 6 (0.00%)	2 / 24 (8.33%)	2 / 25 (8.00%)	1 / 40 (2.50%)	0 / 40 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Immune system disorders
Hypersensitivity
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 24 (4.17%)	0 / 25 (0.00%)	0 / 40 (0.00%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Anal fistula
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 40 (2.50%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haemorrhoids
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	1 / 40 (2.50%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Calculus ureteric
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 40 (0.00%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Calculus urinary
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 7 (0.00%)	0 / 6 (0.00%)	1 / 24 (4.17%)	0 / 25 (0.00%)	0 / 40 (0.00%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hydronephrosis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 40 (0.00%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 24 (0.00%)	1 / 25 (4.00%)	0 / 40 (0.00%)	0 / 40 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	TB Treatment GSK 692342 Group	TB Treatment Saline Group	TB Treated GSK 692342 Group	TB Treated Saline Group	TB Naive GSK 692342 Group	TB Naive Saline Group
Total subjects affected by non serious adverse events
subjects affected / exposed	6 / 7 (85.71%)	2 / 6 (33.33%)	22 / 24 (91.67%)	8 / 25 (32.00%)	39 / 40 (97.50%)	10 / 40 (25.00%)
Investigations
Hepatic enzyme increased
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 7 (0.00%)	0 / 6 (0.00%)	2 / 24 (8.33%)	0 / 25 (0.00%)	0 / 40 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	0	2	0	0	0
Nervous system disorders
Headache
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	2 / 40 (5.00%)	0 / 40 (0.00%)
occurrences all number	0	0	0	0	2	0
General disorders and administration site conditions
Pain
subjects affected / exposed	6 / 7 (85.71%)	1 / 6 (16.67%)	22 / 24 (91.67%)	3 / 25 (12.00%)	39 / 40 (97.50%)	8 / 40 (20.00%)
occurrences all number	6	1	22	3	39	8
Redness
subjects affected / exposed	3 / 7 (42.86%)	0 / 6 (0.00%)	8 / 24 (33.33%)	0 / 25 (0.00%)	10 / 40 (25.00%)	0 / 40 (0.00%)
occurrences all number	3	0	8	0	10	0
Swelling
subjects affected / exposed	3 / 7 (42.86%)	0 / 6 (0.00%)	6 / 24 (25.00%)	1 / 25 (4.00%)	11 / 40 (27.50%)	0 / 40 (0.00%)
occurrences all number	3	0	6	1	11	0
Fatigue
subjects affected / exposed	3 / 7 (42.86%)	2 / 6 (33.33%)	17 / 24 (70.83%)	8 / 25 (32.00%)	36 / 40 (90.00%)	10 / 40 (25.00%)
occurrences all number	3	2	17	8	36	10
Gastrointestinal symptoms
subjects affected / exposed	2 / 7 (28.57%)	0 / 6 (0.00%)	10 / 24 (41.67%)	4 / 25 (16.00%)	16 / 40 (40.00%)	6 / 40 (15.00%)
occurrences all number	2	0	10	4	16	6
Headache (solicited)
subjects affected / exposed	3 / 7 (42.86%)	1 / 6 (16.67%)	18 / 24 (75.00%)	4 / 25 (16.00%)	24 / 40 (60.00%)	6 / 40 (15.00%)
occurrences all number	3	1	18	4	24	6
Malaise
subjects affected / exposed	3 / 7 (42.86%)	2 / 6 (33.33%)	16 / 24 (66.67%)	6 / 25 (24.00%)	35 / 40 (87.50%)	9 / 40 (22.50%)
occurrences all number	3	2	16	6	35	9
Myalgia
subjects affected / exposed	3 / 7 (42.86%)	1 / 6 (16.67%)	18 / 24 (75.00%)	5 / 25 (20.00%)	34 / 40 (85.00%)	7 / 40 (17.50%)
occurrences all number	3	1	18	5	34	7
Temperature/(Axillary)
subjects affected / exposed	4 / 7 (57.14%)	1 / 6 (16.67%)	10 / 24 (41.67%)	0 / 25 (0.00%)	17 / 40 (42.50%)	0 / 40 (0.00%)
occurrences all number	4	1	10	0	17	0
Musculoskeletal and connective tissue disorders
Arthralgia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 7 (0.00%)	0 / 6 (0.00%)	3 / 24 (12.50%)	0 / 25 (0.00%)	0 / 40 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	0	3	0	0	0
Infections and infestations
Upper respiratory tract infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 7 (0.00%)	0 / 6 (0.00%)	3 / 24 (12.50%)	0 / 25 (0.00%)	4 / 40 (10.00%)	3 / 40 (7.50%)
occurrences all number	0	0	3	0	4	3
Gastroenteritis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 7 (0.00%)	0 / 6 (0.00%)	0 / 24 (0.00%)	0 / 25 (0.00%)	2 / 40 (5.00%)	1 / 40 (2.50%)
occurrences all number	0	0	0	0	2	1
Nasopharyngitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 7 (0.00%)	0 / 6 (0.00%)	2 / 24 (8.33%)	0 / 25 (0.00%)	1 / 40 (2.50%)	0 / 40 (0.00%)
occurrences all number	0	0	2	0	1	0
Urinary tract infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 7 (0.00%)	0 / 6 (0.00%)	2 / 24 (8.33%)	0 / 25 (0.00%)	0 / 40 (0.00%)	0 / 40 (0.00%)
occurrences all number	0	0	2	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

14 May 2012

• At the European Medicines Agency’s (EMA) request, GSK Biologicals has updated its procedure for emergency unblinding during the conduct of a clinical study. According to the revised procedure, the responsibility and the decision to break the treatment code in emergency situations resides solely with the investigator and consequently, the investigator will have full authority to break the treatment code. • Change in the number of participating countries in this study. • It has been clarified that TB treatment for subjects belonging to the TB-treatment cohort will be provided independent of this study. • Additional minor modifications have been implemented.

18 Feb 2013

This amendment aims to correct the centre-specific information provided in the protocol. However, as centre-specific information is available in other documents included in the clinical trial application, it was decided to remove centre-specific information from the protocol to avoid future amendments in case enrolment of subjects in the TB treated and TB treatment cohorts remains difficult and additional centres/countries might need to be added to the study.

16 Jan 2014

Due to a safety signal identified in the TB treatment cohort (increased local solicited symptoms post-dose 2), the protocol was amended to include exploratory testing on blood samples taken at Days 0, 7, 30, 37, 60 and 210.

Were there any global interruptions to the trial? Yes

Date	Interruption	Restart date
10 Apr 2014	A safety signal was observed during a planned interim safety review. In consequence the trial was put on hold. After careful consideration further conduct of this safety study is not considered the best course of action and enrolment in the study was terminated.	-

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A phase II observer blind, randomised, controlled study to evaluate the safety, reactogenicity and immunogenicity of GSK Biologicals’ candidate tuberculosis vaccine GSK 692342 when administered to adults aged 18 to 59 years with TB disease.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of subjects with solicited local symptoms

Primary: Number of subjects with solicited local symptoms

Primary: Number of subjects with solicited general symptoms

Primary: Number of subjects with solicited general symptoms

Primary: Number of subjects with adverse events (AEs)

Primary: Number of subjects with adverse events (AEs)

Primary: Number of subjects with serious adverse events (SAEs)

Primary: Number of subjects with serious adverse events (SAEs)

Secondary: Number of subjects with anti-mycobacterium tuberculosis fusion protein M72 antibodies.

Secondary: Number of subjects with anti-mycobacterium tuberculosis fusion protein M72 antibodies.

Secondary: Concentrations of mycobacterium tuberculosis fusion protein M72.

Secondary: Concentrations of mycobacterium tuberculosis fusion protein M72.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of the different immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of the different immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing 2 or more immune markers among 6.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing 2 or more immune markers among 6.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD4+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing at least 2 immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing at least 2 immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing 2 or more immune markers among 6.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing 2 or more immune markers among 6.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Secondary: Frequency of M72-specific CD8+ T cells per million cells expressing any combination of immune markers.

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A phase II observer blind, randomised, controlled study to evaluate the safety, reactogenicity and immunogenicity of GSK Biologicals’ candidate tuberculosis vaccine GSK 692342 when administered to adults aged 18 to 59 years with TB disease.