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Safety and Efficacy of Oral Immunomodulator in Tuberculosis (TB) and TB/HIV Patients

Primary Purpose

Tuberculosis

Status

Completed

Phase

Phase 2

Locations

Ukraine

Study Type

Interventional

Intervention

V-5 immunitor

About this trial

This is an interventional treatment trial for Tuberculosis focused on measuring Mycobacterium, MDR-TB, XDR-TB, HIV, HCV

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Subjects who are at least 18 years old and are willing and capable of providing written-informed consent.
Both men and non-pregnant women will be included.
One group of 30 patients will have HIV.
Another group of 30 patients will have drug-resistant TB (MDR or XDR).
Remaining 60 patients will have drug-sensitive TB of which 30 will be assigned to placebo.
TB infection documented prior to Study Entry by either the presence of TB rapid test or sputum smear positive for acid-fast bacilli (AFB).
At least two independent tests are sought to confirm TB diagnosis.
Agreement to participate in the study and to give a sample of blood for HIV testing.

Exclusion Criteria:

Subjects who have already taken V5 in prior trial and those without baseline data.
Those who met inclusion criteria can be retrospectively enrolled.
Those who are re-treated and relapsed will be eligible as long as they are on the same drug regimen as the rest of patients.
Pregnant or breast-feeding women are excluded.
Subjects who have taken anti-retroviral drugs or immunomodulatory therapies within 2 months prior to Entry:
- systemic corticosteroids
- immune globulin (IV gamma globulin, IVIG)
- interferons,
- interleukins
- pentoxifylline (Trental)
- thalidomide
- filgrastim (G-CSF)
- sargramostim (GM-CSF)
- dinitrochlorobenzene (DNCB)
- thymosin alpha 1 (thymosin alpha)
- thymopentin
- inosiplex (Isoprinosine)
- polyribonucleoside (Ampligen)
- ditiocarb sodium (Imuthiol)
- any locally available immune modulators
- and any other therapeutic or preventive vaccine.
Subjects requiring concurrent participation in another experimental research treatment study, or who received an experimental agent within four weeks prior to Study Entry.
Medical conditions that in the opinion of the local investigator, may obscure the proper observation of the safety or activity of the study treatment; including any acute medical condition of unknown etiology or recent surgery prior to Entry.
Medical conditions such as active alcohol or substance abuse, or psychological issues that in the opinion of the local investigator, would interfere with adherence to the requirements of this study.

Sites / Locations

Lisichansk TB Dispensary

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Immunomodulator intervention

placebo

Arm Description

Two cohorts or arms of at least 60 subjects each (total 120) with pulmonary TB positive for sputum AFB smear will be randomized in a 1:1 ratio to receive once-daily, tablet of V-5 immunitor in combination with standard ATT for 2 months followed by ATT outside of trial for next 4 months or however long it needs to be.

Control Cohort 1 (60 subjects) will receive standard first-line ATT regimen: (daily Isoniazide (H) 150mg, Rifampicin (R) 300mg, Ethambutol (E) 400mg, and Pyrazinamide (Z) 400mg during first 2 months, followed by H/R three times per week for the next 4 months. Patients also will receive placebo preparation, appearing identical to V-5 immunitor, taken once daily 30 minutes prior or after meal for 2 months

Outcomes

Primary Outcome Measures

primary endpoint: sputum smear conversion

Sputum smear conversion at monthly intervals timepoint Rates of pulmonary healing by chest X-ray at the end of study

Secondary Outcome Measures

liver function

To determine the safety of V5+ATT versus ATT+placebo in TB-infected subjects, Standard parameters, e.g., ALT and bilirubin, liver size will be measured.

quality of life

Measure changes in quality of life by TB score questionnaire

hematology parameters

Measure CBC by standard routine methods

weight gain

Measure changes in body weight

Full Information

NCT ID

NCT01222338

First Posted

June 30, 2010

Last Updated

August 2, 2012

Sponsor

Lisichansk Regional Tuberculosis Dispensary

Collaborators

National Medical University, Ukraine, Immunitor USA Inc.

1. Study Identification

Unique Protocol Identification Number

NCT01222338

Brief Title

Safety and Efficacy of Oral Immunomodulator in Tuberculosis (TB) and TB/HIV Patients

Official Title

Phase 2 Placebo-controlled, Randomized Study of Oral Immunomodulator in TB and TB/HIV Patients

Study Type

Interventional

2. Study Status

Record Verification Date

August 2012

Overall Recruitment Status

Completed

Study Start Date

January 2010 (undefined)

Primary Completion Date

December 2010 (Actual)

Study Completion Date

January 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Lisichansk Regional Tuberculosis Dispensary

Collaborators

National Medical University, Ukraine, Immunitor USA Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Treatment of multidrug-resistant TB (MDR-TB) is 100 times more expensive than treatment of drug-susceptible TB, requiring intensive clinical management for prolonged time (18-24 months) and more toxic treatment course. In prior open label study the investigators have shown that adding V-5 Immunitor (V5), can reduce treatment duration to one month and enhance by 4-5 fold the efficacy of TB drugs. Furthermore, V5 has been shown to reverse or reduce liver damage caused by chemotherapy. The cost of V5 will be very modest. The investigators propose to conduct placebo-controlled clinical trial in patients with treatment refractory TB so that the clinical benefit of V5 is confirmed.

Detailed Description

The first-diagnosed Mycobacterium tuberculosis infection (TB) is curable with the first line of anti-tuberculosis drugs (ATT) in over 90% of cases within 6 months. The treatment of TB, refractory to conventional ATT, requires the deployment of second line TB drugs. This represents a significant challenge, particularly in resource-poor countries. The incidence of TB in Ukraine prior to 1992 was about 40 cases per 100,000 people. Ten years later, TB cases increased to over 80/100,000, with mortality doubled from 10.2/100,000 to 21.6/100,000. Drug-resistant TB is now common in Ukraine. Isoniazid and rifampicin resistance, which defines the MDR-TB, has been found in 44% and 32.9% of TB isolates. The first Ukrainian case of HIV was reported in 1987. Today, Ukraine has the highest HIV rate in the Eastern Europe, with increasing proportion of dual infection. For example, in 2002 the prevalence of TB and HIV co-infection was 6.3%, but in 2006 at least 15.5 % of TB patients had HIV co-infection. It is clear that alternative and improved treatment options are needed. If such an intervention is found, the impact on the healthcare and clinical management of treatment-refractory TB and TB-HIV patients will be tremendous. The significant efforts are directed at finding new drugs and vaccines against TB. Immune-based interventions are actively sought as an adjunct therapy to conventional ATT. In earlier study the investigators have accidentally observed that when patients with chronic hepatitis C and HIV-TB were given V5 together with TB drugs it resulted in negative sputum conversion in 95% of patients within one month. This startling finding had prompted this study. The aim of the present study is to compare the clinical benefit of TB therapy in combination with V5 versus combination of placebo with ATT in a representative population of patients who are poorly manageable due to relapsing TB, MDR-TB, or TB-HIV co-infection.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Tuberculosis

Keywords

Mycobacterium, MDR-TB, XDR-TB, HIV, HCV

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

123 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Immunomodulator intervention

Arm Type

Active Comparator

Arm Description

Arm Title

placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Biological

Intervention Name(s)

V-5 immunitor

Other Intervention Name(s)

V5, V-5 immunitor

Intervention Description

once per day dosing for 2 months

Primary Outcome Measure Information:

Title

primary endpoint: sputum smear conversion

Description

Sputum smear conversion at monthly intervals timepoint Rates of pulmonary healing by chest X-ray at the end of study

Time Frame

12 months

Secondary Outcome Measure Information:

Title

liver function

Description

To determine the safety of V5+ATT versus ATT+placebo in TB-infected subjects, Standard parameters, e.g., ALT and bilirubin, liver size will be measured.

Time Frame

12 months

Title

quality of life

Description

Measure changes in quality of life by TB score questionnaire

Time Frame

12 months

Title

hematology parameters

Description

Measure CBC by standard routine methods

Time Frame

12 months

Title

weight gain

Description

Measure changes in body weight

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Subjects who are at least 18 years old and are willing and capable of providing written-informed consent. Both men and non-pregnant women will be included. One group of 30 patients will have HIV. Another group of 30 patients will have drug-resistant TB (MDR or XDR). Remaining 60 patients will have drug-sensitive TB of which 30 will be assigned to placebo. TB infection documented prior to Study Entry by either the presence of TB rapid test or sputum smear positive for acid-fast bacilli (AFB). At least two independent tests are sought to confirm TB diagnosis. Agreement to participate in the study and to give a sample of blood for HIV testing. Exclusion Criteria: Subjects who have already taken V5 in prior trial and those without baseline data. Those who met inclusion criteria can be retrospectively enrolled. Those who are re-treated and relapsed will be eligible as long as they are on the same drug regimen as the rest of patients. Pregnant or breast-feeding women are excluded. Subjects who have taken anti-retroviral drugs or immunomodulatory therapies within 2 months prior to Entry: systemic corticosteroids immune globulin (IV gamma globulin, IVIG) interferons, interleukins pentoxifylline (Trental) thalidomide filgrastim (G-CSF) sargramostim (GM-CSF) dinitrochlorobenzene (DNCB) thymosin alpha 1 (thymosin alpha) thymopentin inosiplex (Isoprinosine) polyribonucleoside (Ampligen) ditiocarb sodium (Imuthiol) any locally available immune modulators and any other therapeutic or preventive vaccine. Subjects requiring concurrent participation in another experimental research treatment study, or who received an experimental agent within four weeks prior to Study Entry. Medical conditions that in the opinion of the local investigator, may obscure the proper observation of the safety or activity of the study treatment; including any acute medical condition of unknown etiology or recent surgery prior to Entry. Medical conditions such as active alcohol or substance abuse, or psychological issues that in the opinion of the local investigator, would interfere with adherence to the requirements of this study.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dmytro Butov, MD

Organizational Affiliation

Kharkiv National Medical University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Lisichansk TB Dispensary

City

Lisichansk

State/Province

Luhansk

ZIP/Postal Code

20001

Country

Ukraine

12. IPD Sharing Statement

Citations:

Citation

DOI 10.2217/imt.12.59

Results Reference

result

PubMed Identifier

27868466

Citation

Batbold U, Butov DO, Kutsyna GA, Damdinpurev N, Grinishina EA, Mijiddorj O, Kovolev ME, Baasanjav K, Butova TS, Sandagdorj M, Batbold O, Tseveendorj A, Chunt E, Zaitzeva SI, Stepanenko HL, Makeeva NI, Mospan IV, Pylypchuk VS, Rowe JL, Nyasulu P, Jirathitikal V, Bain AI, Tarakanovskaya MG, Bourinbaiar AS. Double-blind, placebo-controlled, 1:1 randomized Phase III clinical trial of Immunoxel honey lozenges as an adjunct immunotherapy in 269 patients with pulmonary tuberculosis. Immunotherapy. 2017 Jan;9(1):13-24. doi: 10.2217/imt-2016-0079. Epub 2016 Nov 21.

Results Reference

derived

PubMed Identifier

21182457

Citation

Arjanova OV, Prihoda ND, Yurchenko LV, Sokolenko NI, Frolov VM, Tarakanovskaya MG, Batdelger D, Jirathitikal V, Bourinbaiar AS. Adjunct oral immunotherapy in patients with re-treated, multidrug-resistant or HIV-coinfected TB. Immunotherapy. 2011 Feb;3(2):181-91. doi: 10.2217/imt.10.96. Epub 2010 Dec 24.

Results Reference

derived

Links:

URL

http://omicsonline.org/2157-7560/2157-7560-1-103.php

Description

Phase 2 trial of V-5 Immunitor (V5) in patients with chronic hepatitis C co-infected with HIV and Mycobacterium tuberculosis

URL

http://www.futuremedicine.com/doi/abs/10.2217/imt.12.59

Description

Final results of imm01 study

URL

http://www.omicsonline.org/searchresult.php

Description

doi: 10.4172/2161-1068.S1-001 Therapeutic Vaccination of Treatment-Failed TB Patients on "Palliative" Support Consisting of Isoniazid and Rifampicin

URL

http://www.ncbi.nlm.nih.gov/pubmed/21244690

Description

Phase IIb randomized trial of adjunct immunotherapy in patients with first-diagnosed tuberculosis, relapsed and multi-drug-resistant (MDR) TB.

URL

http://www.ncbi.nlm.nih.gov/pubmed/22397570

Description

Immune approaches in tuberculosis therapy: a brief overview.

Learn more about this trial

Safety and Efficacy of Oral Immunomodulator in Tuberculosis (TB) and TB/HIV Patients

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