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Trial record 13 of 141 for:    MPL

A Study of the Efficacy and Safety of the LEISH-F2 + MPL-SE Vaccine for Treatment of Cutaneous Leishmaniasis

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ClinicalTrials.gov Identifier: NCT01011309
Recruitment Status : Completed
First Posted : November 11, 2009
Results First Posted : November 18, 2013
Last Update Posted : December 11, 2013
Sponsor:
Information provided by (Responsible Party):
IDRI

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cutaneous Leishmaniasis
Interventions Biological: LEISH-F2 + MPL-SE
Drug: Sodium stibogluconate
Enrollment 45
Recruitment Details Patients with CL were actively recruited from Andean mountain regions endemic for transmission of Leishmania peruviana. Patients were treated in a medical clinic at the Instituto de Medicina Tropical ‘Alexander von Humboldt’, Universidad Peruana Cayetano Heredia, Lima, Peru.
Pre-assignment Details All eligible patients were randomized to treatment groups. One patient was mistakenly randomized (ineligible) and was not treated.
Arm/Group Title Immunotherapy v1.4/1.5 Immunotherapy v1.6 Chemotherapy
Hide Arm/Group Description 10 mcg LEISH-F2 antigen + 25 mcg MPL-SE adjuvant given as three subcutaneous injections on Days 0, 28, and 56. 10 mcg LEISH-F2 antigen + 25 mcg MPL-SE adjuvant given as three subcutaneous injections on Days 0, 14, and 28. Sodium stibogluconate (SSG) given 20 mg/kg/day IV for 20 days.
Period Title: Overall Study
Started 14 10 21
Completed 12 7 16
Not Completed 2 3 5
Reason Not Completed
Adverse Event             2             1             2
Lack of Efficacy             0             1             0
Protocol Violation             0             1             3
Arm/Group Title Immunotherapy v1.4/1.5 Immunotherapy v1.6 Chemotherapy Total
Hide Arm/Group Description 10 mcg LEISH-F2 antigen + 25 mcg MPL-SE adjuvant given as three subcutaneous injections on Days 0, 28, and 56. 10 mcg LEISH-F2 antigen + 25 mcg MPL-SE adjuvant given as three subcutaneous injections on Days 0, 14, and 28. Sodium stibogluconate (SSG) given 20 mg/kg/day IV for 20 days. Total of all reporting groups
Overall Number of Baseline Participants 14 10 21 45
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 10 participants 21 participants 45 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
14
 100.0%
10
 100.0%
20
  95.2%
44
  97.8%
>=65 years
0
   0.0%
0
   0.0%
1
   4.8%
1
   2.2%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 10 participants 21 participants 45 participants
38.3  (14.2) 32.7  (6.8) 40.2  (16.0) 38.0  (14.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 10 participants 21 participants 45 participants
Female
5
  35.7%
5
  50.0%
8
  38.1%
18
  40.0%
Male
9
  64.3%
5
  50.0%
13
  61.9%
27
  60.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Peru Number Analyzed 14 participants 10 participants 21 participants 45 participants
14 10 21 45
1.Primary Outcome
Title Date of Clinical Cure
Hide Description Efficacy of immunotherapy with the LEISH-F2 + MPL-SE vaccine was compared to the efficacy of chemotherapy with sodium stibogluconate in the treatment of CL. Efficacy is measured by the date of clinical cure.
Time Frame Day 84
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population: All patients who received all three study injections if in the immunotherapy groups or at least 15 injections of SSG if in the chemotherapy group, and completed the Day 56 visit (Immunotherapy v1.6), the Day 84 visit (Immunotherapy v1.4/1.5), or the Day 56 or Day 84 visit (Chemotherapy group).
Arm/Group Title Immunotherapy v1.4/1.5 Immunotherapy v1.6 Chemotherapy
Hide Arm/Group Description:
10 mcg LEISH-F2 antigen + 25 mcg MPL-SE adjuvant given as three subcutaneous injections on Days 0, 28, and 56.
10 mcg LEISH-F2 antigen + 25 mcg MPL-SE adjuvant given as three subcutaneous injections on Days 0, 14, and 28.
Sodium stibogluconate (SSG) given 20 mg/kg/day IV for 20 days.
Overall Number of Participants Analyzed 12 7 16
Measure Type: Number
Unit of Measure: participants
Clinical cure by Day 84 without rescue treatment 2 2 15
Clinical cure by Day 84 with rescue treatment 10 5 1
2.Primary Outcome
Title Adverse Events of Grade 1 Severity or Higher Occurring in ≥ 3 Patients During Active Treatment Phase of the Study.
Hide Description Safety of immunotherapy with the vaccine was compared to the safety of chemotherapy with sodium stibogluconate. All adverse events are listed regardless of relatedness.
Time Frame Day 0 through Day 84
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: All patients who received at least one study injection.
Arm/Group Title Immunotherapy v1.4/1.5 Immunotherapy v1.6 Chemotherapy
Hide Arm/Group Description:
10 mcg LEISH-F2 antigen + 25 mcg MPL-SE adjuvant given as three subcutaneous injections on Days 0, 28, and 56.
10 mcg LEISH-F2 antigen + 25 mcg MPL-SE adjuvant given as three subcutaneous injections on Days 0, 14, and 28.
Sodium stibogluconate (SSG) given 20 mg/kg/day IV for 20 days.
Overall Number of Participants Analyzed 14 10 21
Measure Type: Number
Unit of Measure: participants
Injection site erythema 10 9 0
Injection site induration 8 10 0
Injection site pain 8 10 0
Superinfection bacterial 4 0 0
ALT increased 8 4 10
Alkaline phosphatase increased 5 1 1
Total bilirubin increased 4 1 3
Hemoglobin decreased 3 0 7
WBC decreased 4 1 10
Headache 3 3 5
Nausea 0 0 3
3.Secondary Outcome
Title IgG Antibodies and T-cell Cytokine Responses (IFN-g and IL-10)
Hide Description Immunogenicity of the vaccine was evaluated by measuring IgG antibody and T-cell responses to the LEISH-F2 protein and soluble Leishmania antigen (SLA). IgG antibodies were measured by ELISA and T-cell cytokine responses (IFN-g and IL-10) were measured by Luminex. Data is presented as median Post:Pre ratios comparing Days 56/84 or 168 to baseline at Day 0.
Time Frame Days 0, 56 or 84, and 168
Hide Outcome Measure Data
Hide Analysis Population Description
Per-protocol population: patients who received all three study injections (immunotherapy groups) or at least 15 SSG injections (chemotherapy group) and completed the Day 84 or Day 56 visit.
Arm/Group Title Immunotherapy v1.4/1.5 Immunotherapy v1.6 Chemotherapy
Hide Arm/Group Description:
10 mcg LEISH-F2 antigen + 25 mcg MPL-SE adjuvant given as three subcutaneous injections on Days 0, 28, and 56.
10 mcg LEISH-F2 antigen + 25 mcg MPL-SE adjuvant given as three subcutaneous injections on Days 0, 14, and 28.
Sodium stibogluconate (SSG) given 20 mg/kg/day IV for 20 days.
Overall Number of Participants Analyzed 12 7 16
Median (Full Range)
Unit of Measure: Relative ELISA Units
IgG antibody to LEISH-F2 - Day 56
NA [1] 
(NA to NA)
84.56
(40.99 to 409.8)
2.004
(0.392 to 37.02)
IgG antibody to LEISH-F2 - Day 84
76.72
(31.19 to 577.1)
NA [2] 
(NA to NA)
0.662
(0.176 to 104.3)
IgG antibody to LEISH-F2 - Day 168
23.93
(6.74 to 159.6)
10.26
(9.11 to 80.75)
0.74
(0.24 to 1.29)
IgG antibody to SLA - Day 56
NA [1] 
(NA to NA)
1.36
(0.46 to 3.14)
0.59
(0.17 to 1.44)
IgG antibody to SLA - Day 84
1.6
(0.84 to 4.43)
NA [2] 
(NA to NA)
0.54
(0.11 to 3.12)
IgG antibody to SLA - Day 168
0.63
(0.15 to 2.88)
0.95
(0.08 to 1.19)
0.33
(0.05 to 0.89)
IFN-g response to LEISH-F2 - Day 56
NA [1] 
(NA to NA)
4.97
(0.354 to 38.36)
1.09
(0.003 to 34.71)
IFN-g response to LEISH-F2 - Day 84
0.92
(0.042 to 19.13)
NA [2] 
(NA to NA)
1.333
(0.073 to 296.8)
IFN-g response to LEISH-F2 - Day 168
1.00
(0.04 to 4.76)
2.06
(0.41 to 11.3)
0.82
(0.15 to 19.6)
IFN-g response to SLA - Day 56
NA [1] 
(NA to NA)
0.87
(0.09 to 6.1)
0.84
(0.01 to 75.3)
IFN-g response to SLA - Day 84
0.27
(0.02 to 39.7)
NA [2] 
(NA to NA)
0.89
(0.09 to 29.8)
IFN-g response to SLA - Day 168
0.2
(0.01 to 76.5)
0.31
(0 to 2.5)
0.69
(0.05 to 3.94)
IL-10 response to LEISH-F2 - Day 56
NA [1] 
(NA to NA)
3.16
(0.4 to 12.8)
1.22
(0.06 to 8.73)
IL-10 response to LEISH-F2 - Day 84
1.44
(0.57 to 47.2)
NA [2] 
(NA to NA)
1.17
(0.06 to 18.9)
IL-10 response to LEISH-F2 - Day 168
2.19
(0.16 to 27.5)
0.9
(0.44 to 3.48)
1.03
(0.08 to 4.91)
IL-10 response to SLA - Day 56
NA [1] 
(NA to NA)
1.02
(0.64 to 2.68)
0.69
(0.03 to 7.44)
IL-10 response to SLA - Day 84
0.63
(0.15 to 25.2)
NA [2] 
(NA to NA)
0.92
(0.04 to 9.85)
IL-10 response to SLA - Day 168
0.952
(0.062 to 308.9)
0.565
(0.294 to 1.068)
0.763
(0.177 to 3.737)
[1]
Immunogenicity not measured at Day 56 in Immunotherapy v1.4/1.5.
[2]
Immunogenicity not measured at Day 84 in Immunotherapy v1.6.
Time Frame Day 0 through Day 336.
Adverse Event Reporting Description All SAEs are listed regardless of relatedness. Other adverse events listed are considered possibly, probably, or definitely related to study vaccination or chemotherapy.
 
Arm/Group Title Immunotherapy v1.4/1.5 Immunotherapy v1.6 Chemotherapy
Hide Arm/Group Description 10 mcg LEISH-F2 antigen + 25 mcg MPL-SE adjuvant given as three subcutaneous injections on Days 0, 28, and 56. 10 mcg LEISH-F2 antigen + 25 mcg MPL-SE adjuvant given as three subcutaneous injections on Days 0, 14, and 28. Sodium stibogluconate (SSG) given 20 mg/kg/day IV for 20 days.
All-Cause Mortality
Immunotherapy v1.4/1.5 Immunotherapy v1.6 Chemotherapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Immunotherapy v1.4/1.5 Immunotherapy v1.6 Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/14 (7.14%)      0/10 (0.00%)      1/21 (4.76%)    
Injury, poisoning and procedural complications       
Hospitalization due to Antimonial Toxicity  [1]  0/14 (0.00%)  0 0/10 (0.00%)  0 1/21 (4.76%)  1
Hospitalization due to Grade 3 Cellulitis  [2]  1/14 (7.14%)  1 0/10 (0.00%)  0 0/21 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Unrelated to vaccination. Headache, nausea, vomiting, abdominal pain and oral discomfort. Lab tests: potassium 2.1mmol/L (Grade 4); AST 66U/L (Grade 1); ALT 35U/L (Grade 1); WBC 3900/mm3 (Grade 1); hgb 10.9g/dL (Grade 1); platelets 65K/mm3 (Grade 2).
[2]
Unrelated to study vaccination. First and second degree burns caused by spilled hot water on left thigh and knee. The subject was treated immediately; pain was well controlled and subsided within 24 hours.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Immunotherapy v1.4/1.5 Immunotherapy v1.6 Chemotherapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   13/14 (92.86%)      10/10 (100.00%)      21/21 (100.00%)    
Gastrointestinal disorders       
Diarrhoea  1  0/14 (0.00%)  0 1/10 (10.00%)  1 0/21 (0.00%)  0
Nausea  1  0/14 (0.00%)  0 0/10 (0.00%)  0 3/21 (14.29%)  3
General disorders       
Face oedema  1  1/14 (7.14%)  1 0/10 (0.00%)  0 0/21 (0.00%)  0
Injection site erythema  1  10/14 (71.43%)  13 9/10 (90.00%)  21 0/0  0
Injection site induration  1  8/14 (57.14%)  9 10/10 (100.00%)  21 0/0  0
Injection site pain  1  8/14 (57.14%)  12 10/10 (100.00%)  25 0/0  0
Malaise  1  0/14 (0.00%)  0 2/10 (20.00%)  3 0/21 (0.00%)  0
Infections and infestations       
Febrile infection  1  0/14 (0.00%)  0 1/10 (10.00%)  1 0/21 (0.00%)  0
Herpes zoster  1  0/14 (0.00%)  0 0/10 (0.00%)  0 2/21 (9.52%)  2
Investigations       
ALT increased  1  8/14 (57.14%)  8 3/10 (30.00%)  3 9/21 (42.86%)  10
Blood alkaline phosphatase increased  1  2/14 (14.29%)  2 0/10 (0.00%)  0 2/21 (9.52%)  2
Blood bilirubin increased  1  2/14 (14.29%)  4 1/10 (10.00%)  1 3/21 (14.29%)  3
Blood potassium decreased  1  0/14 (0.00%)  0 0/10 (0.00%)  0 4/21 (19.05%)  4
Blood sodium increased  1  0/14 (0.00%)  0 0/10 (0.00%)  0 2/21 (9.52%)  2
Haemoglobin decreased  1  2/14 (14.29%)  3 0/10 (0.00%)  0 7/21 (33.33%)  7
Platelet count increased  1  0/14 (0.00%)  0 2/10 (20.00%)  2 0/21 (0.00%)  0
Superinfection bacterial  1  1/14 (7.14%)  1 0/10 (0.00%)  0 0/21 (0.00%)  0
WBC decreased  1  2/14 (14.29%)  2 0/10 (0.00%)  0 10/21 (47.62%)  10
Musculoskeletal and connective tissue disorders       
Musculoskeletal pain  1  0/14 (0.00%)  0 0/10 (0.00%)  0 3/21 (14.29%)  3
Myalgia  1  0/14 (0.00%)  0 1/10 (10.00%)  1 1/21 (4.76%)  1
Nervous system disorders       
Headache  1  1/14 (7.14%)  1 2/10 (20.00%)  4 5/21 (23.81%)  5
Paraesthesia  1  0/14 (0.00%)  0 1/10 (10.00%)  1 0/21 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
A total of 150 patients was planned, including age de-escalation to adolescents after the first 60 adults enrolled. Owing to slow recruitment and insufficient evidence of efficacy in the immunotherapy group, enrollment was closed early.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
IDRI encourages publication in peer-reviewed medical journals and will not unduly withhold permission to publish. However, all proposed publications, papers, abstracts or written materials related to the study or an outline of any oral presentation, shall be submitted to and coordinated by IDRI to assure that no proprietary information is presented and that authorship is fairly represented.
Results Point of Contact
Name/Title: Jill Ashman, MSc, Associate Director of Clinical Operations
Organization: IDRI
Phone: 206-858-6041
Responsible Party: IDRI
ClinicalTrials.gov Identifier: NCT01011309     History of Changes
Other Study ID Numbers: IDRI-LCVTC-202
First Submitted: November 9, 2009
First Posted: November 11, 2009
Results First Submitted: September 16, 2013
Results First Posted: November 18, 2013
Last Update Posted: December 11, 2013