Leprosy Skin Test Antigens Trial

Two New Leprosy Skin Test Antigens: MLSA-LAM and MLCwA Phase II Study in a Leprosy-Endemic Region

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00128193

Enrollment

260

Registered

2005-08-09

Start date

2002-04-30

Completion date

2009-09-30

Last updated

2014-12-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Leprosy

Keywords

leprosy, Mycobacterium leprae, Hansen's Disease, skin test, Nepal

Brief summary

The purpose of this study is to see how healthy people and leprosy patients react to 2 new skin tests for detecting leprosy. The study will evaluate the new skin tests that may aid in measuring the number of people exposed to leprosy and enable its diagnosis and treatment at an earlier stage. Participant's ages 18-60 living in Kathmandu, Nepal will be enrolled. Stages A and B of the study will use the skin test in healthy volunteers. Stage C will use the skin test in high risk volunteers (including individuals with leprosy), healthy individuals in contact with leprosy patients and individuals with tuberculosis (TB, lung disease). Study procedures will include injections, physical exam, and blood testing. Injection sites will be checked several times during the participant's study involvement (5 hours of time spread over approximately 1 month). Volunteers screened for the study, which have leprosy or tuberculosis will be treated or referred for treatment.

Detailed description

This double-blind Phase II clinical trial will be conducted in 3 stages to evaluate 2 new leprosy skin test antigens, Mycobacterium (M.) leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) and M. leprae Cell Wall Antigen (MLCwA), as diagnostic-epidemiological tools designed to measure incidence of leprosy infection in Kathmandu, Nepal, a leprosy endemic area. Stage A will provide an initial indication of safety of the 2 new test antigens in 10 healthy members of the leprosy endemic population (5 subjects per antigen at 2 dosages each). Stage B will expand this analysis by an additional 90 healthy subjects (45 subjects per antigen). If any subjects in Stage A or B show ulcerations at the 1.0 mcg dose of MLSA-LAM or MLCwA test sites, then only the 0.1 mcg dose will be used for Stage C. The final stage, Stage C, is divided into 2 parts. The first part, Stage C-1, will assess safety of both antigens at the high dose (1.0 mcg) in populations at a higher risk of developing ulcerations at skin test sites. Eighty subjects will be recruited: 20 household contacts of Borderline Lepromatous Leprosy (BL) / Lepromatous Leprosy (LL) leprosy patients, 20 BL/LL leprosy patients, 20 Borderline Tuberculoid Leprosy (BT) / Tuberculoid Leprosy (TT) patients and 20 tuberculosis (TB) patients. The second part, Stage C-1b, is a continuation of Stage C-1 with the same number of subjects recruited from the same groups to assess the reactivity of both antigens at the low dose (0.1 mcg). This study will define a positive skin test reaction for MLSA-LAM and MLCwA, and this definition will be used in estimating sensitivity and specificity for each skin test antigen and dosage. It is expected that the BT/TT leprosy patients and healthy contacts of leprosy patients will have larger indurations at both M. leprae-derived antigen sites and a variable reaction at the tuberculin/Purified Protein Derivative (PPD) site. The non-contacts, BL/LL leprosy patients, and TB patients will have smaller indurations at all leprosy skin test sites and a variable reaction at the tuberculin/PPD site. Finally, the TB patients will react with a large induration at the tuberculin/PPD site. Primary study objectives are to evaluate safety of these 2 new leprosy skin test antigens and to estimate specificity and sensitivity of these skin test antigens in detecting M. leprae infection by: selecting a dosage of the MLSA-LAM and MLCwA antigens that causes minimal induration in healthy non-exposed subjects; selecting a size of induration that will serve as a definition of a positive skin test reaction for MLSA-LAM and MLCwA in leprosy patients; and comparing proportion of positive skin test reactors in healthy subjects to proportion in BT/TT and BL/LL leprosy patients, contacts of leprosy patients, and TB patients. Secondary study objectives are to compare mean size of induration in response to each test antigen in healthy subjects versus BT/TT and BL/LL leprosy patients, contacts of leprosy patients, and TB patients as a measure of specificity and sensitivity; to compare the specificity and sensitivity of the 2 new antigens with tuberculin/PPD in patients with clinical leprosy, contacts of leprosy patients, and healthy unexposed subjects (non-patient contacts); to quantify release of IFN-gamma from lymphocytes in whole blood from leprosy patients, leprosy patient contacts, TB patients, and healthy nonexposed subjects, following in vitro stimulation with leprosy skin test antigens and PPD, using the QuantiFERON-CMI (Cellestis Limited, Valentia California) kit. Results will be compared to the magnitude of the skin test response; and to determine if antibodies against a M. leprae specific anti

Interventions

BIOLOGICALTuberculin, Purified Protein Derivative

A tuberculin skin test used to diagnose latent tuberculosis (TB) infection. 2 TU dose

OTHERMLSA-LAM

Mycobacterium leprae soluble antigen with minimal amounts of immunosuppressive lipoglycans; dosages 0.1 and 1.0 micrograms; administered in sterile diluent 0.9% saline (NaCl).

OTHERMLCwA

Cell wall-associated proteins of Mycobacterium leprae; dosages 0.1 and 1.0 micrograms; administered in sterile diluent 0.9% saline (NaCl).

OTHERPlacebo

Saline (NaCl) serves as a diluent control in Stage A and B only.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

DIAGNOSTIC

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 60 Years

Healthy volunteers

Yes

Inclusion criteria

All Subjects * Between the ages of 18 and 60 years old * Male or female; not less than 30 percent for one gender * Agree to participate in the study after verbal explanation by the physician and nurses, as indicated by signing an informed consent form * Weight greater than 30 Kg (female) and 38 Kg (male) * Available for skin test readings * Nepali residents, including expatriates from India Healthy, Non-Contacts * Healthy (determined by history and physical examination) * No household or working contact with tuberculosis or leprosy patients Contacts of Leprosy Patients * Healthy (determined by history and physical examination) * Household contact of a person with leprosy for at least 6 months duration, and within 6 months of this study, or a person professionally exposed to leprosy for at least 5 years duration, and within 6 months of this study Persons with Leprosy * Having one or more of the following symptoms: 1. Hypopigmented or erythematous skin lesion(s) with definite loss of sensation 2. Damage to the peripheral nerves as demonstrated by palpable thickening with or without impairment of sensation and/or weakness of the muscles of hands, feet or face 3. Presence of acid-fast bacilli in slit skin smears 4. Histological changes diagnostic of leprosy in skin biopsy * Receiving standard multi drug treatment for leprosy or completed treatment for leprosy no more than 4 years prior to study enrollment Persons with Tuberculosis * Having active tuberculosis as defined by one of the following: 1. Extra-pulmonary tuberculosis if confirmed by culture 2. Pulmonary tuberculosis, defined as: * Having a history of a productive cough of more than 3 weeks duration that may be accompanied by night sweats, loss of appetite, haemoptysis, weight loss, chest pain, or shortness of breath, and * Having one or more of the following diagnostic criteria: * Sputum smear-positive, defined as one or more of the following: at least 2 of 3 successive sputum samples positive for acid-fast bacilli by microscopy; or at least one sputum specimen positive and x-ray abnormalities consistent with pulmonary tuberculosis; or at least one positive sputum specimen that is culture positive for Mycobacterium tuberculosis * Sputum smear-negative, defined as three sputum specimens negative for acid-fast bacilli but with x-ray evidence consistent with pulmonary tuberculosis and that does not clear with non-tuberculosis antibiotics; or three sputum samples negative for acid-fast bacilli by microscopy but culture positive for Mycobacterium tuberculosis * Completed the intensive phase of chemotherapy for tuberculosis, but still undergoing the continuation phase of therapy

Exclusion criteria

All subjects * Pregnant (as determined by a urine pregnancy test performed on females of child-bearing age on Day 0, prior to admission into the study) or lactating females * Currently on oral corticosteroid or other immunosuppressive treatment * Cancer, diabetes, or other chronic illness * Extra-pulmonary tuberculosis not confirmed by culture * Known hypersensitivities or allergies * Expatriates other than those from India * Participation in an earlier stage of this study * Concurrent participation in another clinical trial Healthy, Non-Contacts * History of treated tuberculosis or leprosy * Clinical signs of leprosy or tuberculosis * Known contact with persons with leprosy or tuberculosis Healthy Contacts of Leprosy Patients * History of treated tuberculosis or leprosy * Clinical signs of leprosy or tuberculosis Persons with Leprosy * Leprosy patients in reversal reaction or erythema nodosum leprosum (ENL) reaction or those being treated with corticosteroids or thalidomide for these conditions * History of treated tuberculosis * Clinical signs of tuberculosis * Completed full course of standard multidrug treatment (MDT) for leprosy more than 4 years prior to study enrollment Persons with Tuberculosis * History of treated leprosy * Clinical signs of leprosy * Completed full course of standard tuberculosis treatment * Known contact with leprosy patients

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Reactions to the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 0.1 Microgram	Up to 28 Days	Participants returned to the clinic at Days 2 (Group A), 3 (all groups) and 7 (Groups B and C), and at Day 28 if reactions were still present (all groups), for reader measurements of erythema and induration and assessment of other adverse events of pain/tenderness, bleeding, urticaria, infection, or blistering/ulcerating. Participants are counted if they had any measurable erythema or induration, or reported any of the other listed adverse events. Reactions were reported as present or absent, and were not graded for severity.
Number of Participants With the Reaction of Itching to the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 0.1 Microgram	Up to 28 Days	Itching was assessed for participants in Groups B and C only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present. Itching was reported as present or absent, and not graded for severity.
Number of Participants With Reactions to the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 1.0 Microgram	Up to 28 Days	Participants returned to the clinic at Days 2 (Group A), 3 (all groups) and 7 (Groups B and C), and at Day 28 if reactions were still present (all groups), for reader measurements of erythema and induration and assessment of other adverse events of pain/tenderness, bleeding, urticaria, infection, or blistering/ulcerating. Participants are counted if they had any measurable eythema or induration, or reported any of the other listed adverse events. Reactions were reported as present or absent, and were not graded for severity.
Number of Participants With the Reaction of Itching to the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 1.0 Microgram	Up to 28 Days	Itching was assessed for participants in Groups B and C only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present. Itching was reported as present or absent, and not graded for severity.
Number of Participants With Reactions to the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 0.1 Microgram	Up to 28 Days	Participants returned to the clinic at Days 2 (Group A), 3 (all groups) and 7 (Groups B and C), and at Day 28 if reactions were still present (all groups), for reader measurements of erythema and induration and assessment of other adverse events of pain/tenderness, bleeding, urticaria, infection, or blistering/ulcerating. Participants are counted if they had any measurable eythema or induration, or reported any of the other listed adverse events. Reactions were reported as present or absent, and were not graded for severity.
Number of Participants With Reaction of Itching to the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 0.1 Microgram	Up to 28 Days	Itching was assessed for participants in Groups B and C only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present. Itching was reported as present or absent, and not graded for severity.
Number of Participants With Reactions to the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 1.0 Microgram	Up to 28 Days	Participants returned to the clinic at Days 2 (Group A), 3 (all groups) and 7 (Groups B and C), and at Day 28 if reactions were still present (all groups), for reader measurements of erythema and induration and assessment of other adverse events of pain/tenderness, bleeding, urticaria, infection, or blistering/ulcerating. Participants are counted if they had any measurable eythema or induration, or reported any of the other listed adverse events. Reactions were reported as present or absent, and were not graded for severity.
Number of Participants With the Reaction of Itching to the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 1.0 Microgram	Up to 28 Days	Itching was assessed for participants in Groups B and C only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present. Itching was reported as present or absent, and not graded for severity.
Number of Participants With Reactions to the Antigen Purified Protein Derivative (PPD)	Up to 28 Days	Participants returned to the clinic at Days 2 (Group A), 3 (all groups) and 7 (Groups B and C), and at Day 28 if reactions were still present (all groups), for reader measurements of erythema and induration and assessment of other adverse events of pain/tenderness, bleeding, urticaria, infection, or blistering/ulcerating. Participants are counted if they had any measurable eythema or induration, or reported any of the other listed adverse events. Reactions were reported as present or absent, and were not graded for severity.
Number of Participants With the Reaction of Itching to the Antigen Purified Protein Derivative (PPD)	Up to 28 Days	Itching was assessed for participants in Groups B and C only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present. Itching was reported as present or absent, and not graded for severity.
Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 0.1 Micrograms	Day 3	If erythema was present, it was measured in millimeters for participants in Groups C1 and C1b only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present.
Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 1.0 Micrograms	Day 3	If erythema was present, it was measured in millimeters for participants in Groups C1 and C1b only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present.
Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 0.1 Micrograms	Day 3	If erythema was present, it was measured in millimeters for participants in Groups C1 and C1b only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present.
Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 1.0 Micrograms	Day 3	If erythema was present, it was measured in millimeters for participants in Groups C1 and C1b only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present.
Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	Day 3	If erythema was present, it was measured in millimeters for participants in Groups C1 and C1b only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present.
Mean Diameter of Induration at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 0.1 Micrograms	Day 3	If induration was present, it was measured in millimeters at Days 2 (Group A), 3 (all groups) and 7 (Groups B and C), and at Day 28 if reactions were still present (all groups).
Mean Diameter of Induration at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 1.0 Micrograms	Day 2	If induration was present, it was measured in millimeters at Days 2 (Group A), 3 (all groups) and 7 (Groups B and C), and at Day 28 if reactions were still present (all groups).
Mean Diameter of Induration at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 0.1 Micrograms	Day 3	If induration was present, it was measured in millimeters at Days 2 (Group A), 3 (all groups) and 7 (Groups B and C), and at Day 28 if reactions were still present (all groups).
Mean Diameter of Induration at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 1.0 Micrograms	Day 2	If induration was present, it was measured in millimeters at Days 2 (Group A), 3 (all groups) and 7 (Groups B and C), and at Day 28 if reactions were still present (all groups).
Mean Diameter of Induration at Site of Injection With the Antigen Purified Protein Derivative (PPD)	Day 2	If induration was present, it was measured in millimeters at Days 2 (Group A), 3 (all groups) and 7 (Groups B and C), and at Day 28 if reactions were still present (all groups).
Number of Participants With QuantiFERON Responses Based on the Presence or Absence of Induration at the Injection Site for the Antigen MLSA-LAM at Doses of 0.1 Microgram.	Day 0 for QuantiFERON; Days 3, 7, and 28 for induration	Blood collection for the QuantiFERON assessment was at Day 0 prior to antigen administration. Participants are considered to have a positive QuantiFERON response if the result was greater than 0. The categories present the number of participants who are positive or negative by QuantiFERON based on whether or not induration was assessed as present at any of the follow up visit assessments. A fifth category is listed to report the number of participants who were missing either a QuantiFERON result or induration assessment. The categories are mutually exclusive.
Number of Participants With QuantiFERON Responses Based on the Presence or Absence of Induration at the Injection Site for the Antigen MLSA-LAM at Doses of 1.0 Microgram.	Day 0 for QuantiFERON; Days 3, 7, and 28 for induration	Blood collection for the QuantiFERON assessment was at Day 0 prior to antigen administration. Participants are considered to have a positive QuantiFERON response if the result was greater than 0. The categories present the number of participants who are positive or negative by QuantiFERON based on whether or not induration was assessed as present at any of the follow up visit assessments. A fifth category is listed to report the number of participants who were missing either a QuantiFERON result or induration assessment. The categories are mutually exclusive.
Number of Participants With QuantiFERON Responses Based on the Presence or Absence of Induration at the Injection Site for the Antigen MLCwA at Doses of 0.1 Microgram.	Day 0 for QuantiFERON; Days 3, 7, and 28 for induration	Blood collection for the QuantiFERON assessment was at Day 0 prior to antigen administration. Participants are considered to have a positive QuantiFERON response if the result was greater than 0. The categories present the number of participants who are positive or negative by QuantiFERON based on whether or not induration was assessed as present at any of the follow up visit assessments. A fifth category is listed to report the number of participants who were missing either a QuantiFERON result or induration assessment. The categories are mutually exclusive.
Number of Participants With QuantiFERON Responses Based on the Presence or Absence of Induration at the Injection Site for the Antigen MLCwA at Doses of 1.0 Microgram.	Day 0 for QuantiFERON; Days 3, 7, and 28 for induration	Blood collection for the QuantiFERON assessment was at Day 0 prior to antigen administration. Participants are considered to have a positive QuantiFERON response if the result was greater than 0. The categories present the number of participants who are positive or negative by QuantiFERON based on whether or not induration was assessed as present at any of the follow up visit assessments. A fifth category is listed to report the number of participants who were missing either a QuantiFERON result or induration assessment. The categories are mutually exclusive.
Number of Participants With QuantiFERON Responses Based on the Presence or Absence of Induration at the Injection Site for the Antigen PPD.	Day 0 for QuantiFERON; Days 3, 7, and 28 for induration	Blood collection for the QuantiFERON assessment was at Day 0 prior to antigen administration. Participants are considered to have a positive QuantiFERON response if the result was greater than 0. The categories present the number of participants who are positive or negative by QuantiFERON based on whether or not induration was assessed as present at any of the follow up visit assessments. A fifth category is listed to report the number of participants who were missing either a QuantiFERON result or induration assessment. The categories are mutually exclusive.
Number of Participants Positive for Phenolic Glycolipid-1 (PGL-1) by QuantiFERON Results and the Presence or Absence of Induration at the Injection Site for the Antigen MLSA-LAM at Doses of 0.1 Microgram	Day 0 for PGL-1 and QuantiFERON; Days 3, 7, and 28 for induration	Blood was collected at Day 0 prior to antigen administration for the assessment of PGL-1 and QuantiFERON. The mutually exclusive categories present the number of participants positive or negative by the two assays based on presence of induration at any of the follow up visit assessments. Results for PGL-1 of weakly, moderately or strongly positive are grouped as positive. A result greater than 0 is considered positive for QuantiFERON. A fifth category is listed to report the number of participants who were missing either assay result or the induration assessment.
Number of Participants Positive for Phenolic Glycolipid-1 (PGL-1) by QuantiFERON Results and the Presence or Absence of Induration at the Injection Site for the Antigen MLSA-LAM at Doses of 1.0 Microgram	Day 0 for PGL-1 and QuantiFERON; Days 3, 7, and 28 for induration	Blood was collected at Day 0 prior to antigen administration for the assessment of PGL-1 and QuantiFERON. The mutually exclusive categories present the number of participants positive or negative by the two assays based on presence of induration at any of the follow up visit assessments. Results for PGL-1 of weakly, moderately or strongly positive are grouped as positive. A result greater than 0 is considered positive for QuantiFERON. A fifth category is listed to report the number of participants who were missing either assay result or the induration assessment.
Number of Participants Positive for Phenolic Glycolipid-1 (PGL-1) by QuantiFERON Results and the Presence or Absence of Induration at the Injection Site for the Antigen MLCwA at Doses of 0.1 Microgram	Day 0 for PGL-1 and QuantiFERON; Days 3, 7, and 28 for induration	Blood was collected at Day 0 prior to antigen administration for the assessment of PGL-1 and QuantiFERON. The mutually exclusive categories present the number of participants positive or negative by the two assays based on presence of induration at any of the follow up visit assessments. Results for PGL-1 of weakly, moderately or strongly positive are grouped as positive. A result greater than 0 is considered positive for QuantiFERON. A fifth category is listed to report the number of participants who were missing either assay result or the induration assessment.
Number of Participants Positive for Phenolic Glycolipid-1 (PGL-1) by QuantiFERON Results and the Presence or Absence of Induration at the Injection Site for the Antigen MLCwA at Doses of 1.0 Microgram	Day 0 for PGL-1 and QuantiFERON; Days 3, 7, and 28 for induration	Blood was collected at Day 0 prior to antigen administration for the assessment of PGL-1 and QuantiFERON. The mutually exclusive categories present the number of participants positive or negative by the two assays based on presence of induration at any of the follow up visit assessments. Results for PGL-1 of weakly, moderately or strongly positive are grouped as positive. A result greater than 0 is considered positive for QuantiFERON. A fifth category is listed to report the number of participants who were missing either assay result or the induration assessment.
Number of Participants Positive for Phenolic Glycolipid-1 (PGL-1) by QuantiFERON Results and the Presence or Absence of Induration at the Injection Site for the Antigen PPD	Day 0 for PGL-1 and QuantiFERON; Days 3, 7, and 28 for induration	Blood was collected at Day 0 prior to antigen administration for the assessment of PGL-1 and QuantiFERON. The mutually exclusive categories present the number of participants positive or negative by the two assays based on presence of induration at any of the follow up visit assessments. Results for PGL-1 of weakly, moderately or strongly positive are grouped as positive. A result greater than 0 is considered positive for QuantiFERON. A fifth category is listed to report the number of participants who were missing either assay result or the induration assessment.

Countries

Nepal, United States

Participant flow

Recruitment details

Stage A (10) and B (90) participants were recruited from Lalitpur Nursing Campus in Kathmandu, Nepal. All participants for stages C1 (80) and C1b (80) were recruited from either Anandaban Hospital in Kathmandu, Nepal or Patan Hospital in Lalitpur, Nepal. Enrollment occurred between 30Apr2002 and 12Aug2009.

Participants by arm

Arm	Count
A1 - MLSA in Healthy Non-Exposed Participants 5 healthy non-exposed participants received 1.0 mcg of Mycobacterium (M.) leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM), 0.1 mcg of MLSA-LAM, 5 tuberculin units (TU) Purified Protein Derivative(PPD)/Tubersol®, saline (NaCl)	5
A2 - MLC in Healthy Non-Exposed Participants 5 healthy non-exposed participants received 1.0 mcg of M. leprae Cell Wall Antigen (MLCwA), 0.1 mcg of MLCwA, 5 TU Purified Protein Derivative/Tubersol®, saline (NaCl)	5
B1 - MLSA in Healthy Non-Exposed Participants 45 healthy non-exposed participants received 1.0 mcg of MLSA-LAM, 0.1 mcg of MLSA-LAM, 5 TU Purified Protein Derivative/Tubersol®, saline (NaCl)	45
B2 - MLC in Healthy Non-Exposed Participants 45 healthy non-exposed participants received 1.0 mcg of MLCwA, 0.1 mcg of MLCwA, 5 TU Purified Protein Derivative/Tubersol®, saline (NaCl)	45
C1 - High Dose MLSA and MLC in BL/LL Leprosy Patients 20 borderline lepromatous/lepromatous (BL/LL) leprosy patients received 1.0 mcg of MLSA-LAM, 1.0 mcg of MLCwA and 2TU Purified Protein Derivative/RT-23	20
C1 - High Dose MLSA and MLC in BT/TT Leprosy Patients 20 borderline tuberculoid/tuberculoid (BT/TT) leprosy patients received 1.0 mcg of MLSA-LAM, 1.0 mcg of MLCwA and 2TU Purified Protein Derivative/RT-23	20
C1 - High Dose MLSA and MLC in BL/LL Healthy Contacts 20 healthy contacts of BL/LL leprosy patients received 1.0 mcg of MLSA-LAM, 1.0 mcg of MLCwA and 2TU Purified Protein Derivative/RT-23	20
CI - High Dose MLSA and MLC in TB Patients 20 tuberculosis (TB) patients received 1.0 mcg of MLSA-LAM, 1.0 mcg of MLCwA and 2TU Purified Protein Derivative/RT-23	20
C1b - Low Dose MLSA and MLC in BL/LL Leprosy Patients 20 borderline lepromatous/lepromatous (BL/LL) leprosy patients received 0.1 mcg MLSA-LAM, 0.1 mcg MLCwA, 2 TU Purified Protein Derivative/RT-23	20
C1b - Low Dose MLSA and MLC in BT/TT Leprosy Patients 20 borderline tuberculoid/tuberculoid (BT/TT) leprosy patients received 0.1 mcg MLSA-LAM, 0.1 mcg MLCwA, 2 TU Purified Protein Derivative/RT-23.	20
C1b - Low Dose MLSA and MLC in Healthy Contacts 20 healthy contacts of BL/LL leprosy patients received 0.1 mcg MLSA-LAM, 0.1 mcg MLCwA, 2 TU Purified Protein Derivative/RT-23.	20
C1b - Low Dose MLSA and MLC in TB Patients 20 TB patients received 0.1 mcg MLSA-LAM, 0.1 mcg MLCwA, 2 TU Purified Protein Derivative/RT-23.	20
Total	260

Baseline characteristics

Characteristic	A2 - MLC in Healthy Non-Exposed Participants	B1 - MLSA in Healthy Non-Exposed Participants	B2 - MLC in Healthy Non-Exposed Participants	C1 - High Dose MLSA and MLC in BL/LL Leprosy Patients	C1 - High Dose MLSA and MLC in BT/TT Leprosy Patients	C1 - High Dose MLSA and MLC in BL/LL Healthy Contacts	A1 - MLSA in Healthy Non-Exposed Participants	CI - High Dose MLSA and MLC in TB Patients	C1b - Low Dose MLSA and MLC in BL/LL Leprosy Patients	C1b - Low Dose MLSA and MLC in BT/TT Leprosy Patients	C1b - Low Dose MLSA and MLC in Healthy Contacts	C1b - Low Dose MLSA and MLC in TB Patients	Total
Age, Categorical <=18 years	0 Participants	13 Participants	10 Participants	0 Participants	0 Participants	0 Participants	0 Participants	4 Participants	0 Participants	1 Participants	4 Participants	1 Participants	33 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	5 Participants	32 Participants	35 Participants	20 Participants	20 Participants	20 Participants	5 Participants	16 Participants	20 Participants	19 Participants	16 Participants	19 Participants	227 Participants
Age, Continuous	29.4 years STANDARD_DEVIATION 2.9	21.1 years STANDARD_DEVIATION 5.3	23.1 years STANDARD_DEVIATION 6.7	37.5 years STANDARD_DEVIATION 12.3	32.9 years STANDARD_DEVIATION 12.9	32.9 years STANDARD_DEVIATION 11	30.6 years STANDARD_DEVIATION 6.4	26.0 years STANDARD_DEVIATION 7.7	35.2 years STANDARD_DEVIATION 13.1	39.0 years STANDARD_DEVIATION 13.5	30.2 years STANDARD_DEVIATION 12.1	31.1 years STANDARD_DEVIATION 13.1	28.5 years STANDARD_DEVIATION 11.3
Region of Enrollment Nepal	5 participants	45 participants	45 participants	20 participants	20 participants	20 participants	5 participants	20 participants	20 participants	20 participants	20 participants	20 participants	260 participants
Sex: Female, Male Female	4 Participants	14 Participants	8 Participants	6 Participants	6 Participants	7 Participants	4 Participants	7 Participants	5 Participants	4 Participants	14 Participants	5 Participants	84 Participants
Sex: Female, Male Male	1 Participants	31 Participants	37 Participants	14 Participants	14 Participants	13 Participants	1 Participants	13 Participants	15 Participants	16 Participants	6 Participants	15 Participants	176 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk	EG005 affected / at risk	EG006 affected / at risk	EG007 affected / at risk	EG008 affected / at risk	EG009 affected / at risk	EG010 affected / at risk	EG011 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	5 / 5	4 / 5	36 / 45	35 / 45	13 / 20	15 / 20	19 / 20	20 / 20	11 / 20	16 / 20	18 / 20	20 / 20
serious Total, serious adverse events	0 / 5	0 / 5	2 / 45	0 / 45	0 / 20	0 / 20	0 / 20	0 / 20	0 / 20	0 / 20	0 / 20	0 / 20

Outcome results

Primary

Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 0.1 Micrograms

If erythema was present, it was measured in millimeters for participants in Groups C1 and C1b only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present.

Time frame: Day 3

Population: The analysis population is restricted to participants in Group C1b who had measurable erythema at the time of assessment.

Arm	Measure	Value (MEAN)	Dispersion
A1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 0.1 Micrograms	15.1 Millimeters	Standard Deviation 3.3
B1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 0.1 Micrograms	13.0 Millimeters	Standard Deviation 4.6
C1b - Low Dose MLSA and MLC in BL/LL Leprosy Patients	Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 0.1 Micrograms	9.6 Millimeters	Standard Deviation 2.3

Primary

Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 0.1 Micrograms

If erythema was present, it was measured in millimeters for participants in Groups C1 and C1b only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present.

Time frame: Day 7

Population: The analysis population is restricted to participants in Group C1b who had measurable erythema at the time of assessment.

Arm	Measure	Value (MEAN)	Dispersion
A1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 0.1 Micrograms	12.1 Millimeters	Standard Deviation 5
B1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 0.1 Micrograms	12.2 Millimeters	Standard Deviation 3.4
C1b - Low Dose MLSA and MLC in BL/LL Leprosy Patients	Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 0.1 Micrograms	8.9 Millimeters	Standard Deviation 1.4

Primary

Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 1.0 Micrograms

If erythema was present, it was measured in millimeters for participants in Groups C1 and C1b only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present.

Time frame: Day 3

Population: The analysis population is restricted to participants in Group C1 who had measurable erythema at the time of assessment.

Arm	Measure	Value (MEAN)	Dispersion
A1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 1.0 Micrograms	9.0 Millimeters	—
B1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 1.0 Micrograms	20.8 Millimeters	Standard Deviation 2.9
C1b - Low Dose MLSA and MLC in BL/LL Leprosy Patients	Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 1.0 Micrograms	14.7 Millimeters	Standard Deviation 5.7
C1b - Low Dose MLSA and MLC in BT/TT Leprosy Patients	Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 1.0 Micrograms	15.0 Millimeters	Standard Deviation 6.1

Primary

Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 1.0 Micrograms

If erythema was present, it was measured in millimeters for participants in Groups C1 and C1b only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present.

Time frame: Day 7

Population: The analysis population is restricted to participants in Group C1 who had measurable erythema at the time of assessment.

Arm	Measure	Value (MEAN)	Dispersion
A1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 1.0 Micrograms	17.8 Millimeters	Standard Deviation 7
B1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 1.0 Micrograms	16.4 Millimeters	Standard Deviation 5.1
C1b - Low Dose MLSA and MLC in BL/LL Leprosy Patients	Mean Diameter of Erythema at Site of Injection With the Antigen M. Leprae Cell Wall Antigen (MLCwA) at Doses of 1.0 Micrograms	13.8 Millimeters	Standard Deviation 5.3

Primary

Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 0.1 Micrograms

If erythema was present, it was measured in millimeters for participants in Groups C1 and C1b only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present.

Time frame: Day 7

Population: The analysis population is restricted to participants in Group C1b who had measurable erythema at the time of assessment.

Arm	Measure	Value (MEAN)	Dispersion
A1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 0.1 Micrograms	11.3 Millimeters	Standard Deviation 3.4
B1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 0.1 Micrograms	10.3 Millimeters	Standard Deviation 0.8
C1b - Low Dose MLSA and MLC in BL/LL Leprosy Patients	Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 0.1 Micrograms	9.8 Millimeters	Standard Deviation 2.4

Primary

Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 0.1 Micrograms

If erythema was present, it was measured in millimeters for participants in Groups C1 and C1b only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present.

Time frame: Day 3

Population: The analysis population is restricted to participants in Group C1b who had measurable erythema at the time of assessment.

Arm	Measure	Value (MEAN)	Dispersion
A1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 0.1 Micrograms	12.6 Millimeters	Standard Deviation 4.2
B1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 0.1 Micrograms	9.8 Millimeters	Standard Deviation 1.8
C1b - Low Dose MLSA and MLC in BL/LL Leprosy Patients	Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 0.1 Micrograms	9.3 Millimeters	Standard Deviation 0.6

Primary

Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 1.0 Micrograms

If erythema was present, it was measured in millimeters for participants in Groups C1 and C1b only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present.

Time frame: Day 7

Population: The analysis population is restricted to participants in Group C1 who had measurable erythema at the time of assessment.

Arm	Measure	Value (MEAN)	Dispersion
A1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 1.0 Micrograms	16.0 Millimeters	—
B1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 1.0 Micrograms	20.3 Millimeters	Standard Deviation 5.3
C1b - Low Dose MLSA and MLC in BL/LL Leprosy Patients	Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 1.0 Micrograms	13.8 Millimeters	Standard Deviation 6.6
C1b - Low Dose MLSA and MLC in BT/TT Leprosy Patients	Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 1.0 Micrograms	14.3 Millimeters	Standard Deviation 6.6

Primary

Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 1.0 Micrograms

If erythema was present, it was measured in millimeters for participants in Groups C1 and C1b only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present.

Time frame: Day 3

Population: The analysis population is restricted to participants in Group C1 who had measurable erythema at the time of assessment.

Arm	Measure	Value (MEAN)	Dispersion
A1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 1.0 Micrograms	20.0 Millimeters	—
B1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 1.0 Micrograms	23.3 Millimeters	Standard Deviation 4.6
C1b - Low Dose MLSA and MLC in BL/LL Leprosy Patients	Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 1.0 Micrograms	13.0 Millimeters	Standard Deviation 5.9
C1b - Low Dose MLSA and MLC in BT/TT Leprosy Patients	Mean Diameter of Erythema at Site of Injection With the Antigen Mycobacterium (M.) Leprae Soluble Antigen (MLSA)-Lipoarabinomannan (LAM) at Doses of 1.0 Micrograms	14.8 Millimeters	Standard Deviation 6.5

Primary

Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)

If erythema was present, it was measured in millimeters for participants in Groups C1 and C1b only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present.

Time frame: Day 7

Population: The analysis population is restricted to participants in Group C1 and C1b who had measurable erythema at the time of assessment.

Arm	Measure	Value (MEAN)	Dispersion
A1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	18.6 Millimeters	Standard Deviation 5.4
B1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	19.0 Millimeters	Standard Deviation 6.5
C1b - Low Dose MLSA and MLC in BL/LL Leprosy Patients	Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	17.8 Millimeters	Standard Deviation 5.7
C1b - Low Dose MLSA and MLC in BT/TT Leprosy Patients	Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	20.9 Millimeters	Standard Deviation 4.6
C1b - Low Dose MLSA and MLC in Healthy Contacts	Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	16.8 Millimeters	Standard Deviation 4.2
C1b - Low Dose MLSA and MLC in TB Patients	Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	17.1 Millimeters	Standard Deviation 4.3
C1 - High Dose MLSA and MLC in BL/LL Healthy Contacts	Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	16.4 Millimeters	Standard Deviation 6.2
CI - High Dose MLSA and MLC in TB Patients	Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	19.1 Millimeters	Standard Deviation 4.2

Primary

Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)

If erythema was present, it was measured in millimeters for participants in Groups C1 and C1b only, who returned to the clinic at Days 3 and 7, and at Day 28 if reactions were still present.

Time frame: Day 3

Population: The analysis population is restricted to participants in Group C1 and C1b who had measurable erythema at the time of assessment.

Arm	Measure	Value (MEAN)	Dispersion
A1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	20.4 Millimeters	Standard Deviation 9.4
B1 - MLSA in Healthy Non-Exposed Participants	Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	20.7 Millimeters	Standard Deviation 8
C1b - Low Dose MLSA and MLC in BL/LL Leprosy Patients	Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	19.3 Millimeters	Standard Deviation 9.8
C1b - Low Dose MLSA and MLC in BT/TT Leprosy Patients	Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	22.4 Millimeters	Standard Deviation 7.1
C1b - Low Dose MLSA and MLC in Healthy Contacts	Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	18.1 Millimeters	Standard Deviation 6
C1b - Low Dose MLSA and MLC in TB Patients	Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	17.8 Millimeters	Standard Deviation 4.8
C1 - High Dose MLSA and MLC in BL/LL Healthy Contacts	Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	17.6 Millimeters	Standard Deviation 8.1
CI - High Dose MLSA and MLC in TB Patients	Mean Diameter of Erythema at Site of Injection With the Antigen Purified Protein Derivative (PPD)	21.1 Millimeters	Standard Deviation 7

Primary