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

NCT ID: NCT01222338

Last Updated: 2012-08-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 123 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2011-01-31

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.

Conditions

Tuberculosis

Keywords

Mycobacterium; MDR-TB; XDR-TB; HIV; HCV

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Immunomodulator intervention

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.

Group Type: ACTIVE_COMPARATOR

V-5 immunitor

Intervention Type: BIOLOGICAL

once per day dosing for 2 months

placebo

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

Group Type: PLACEBO_COMPARATOR

V-5 immunitor

Intervention Type: BIOLOGICAL

once per day dosing for 2 months

Interventions

V-5 immunitor

once per day dosing for 2 months

Intervention Type: BIOLOGICAL

Other Intervention Names

V5, V-5 immunitor

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.

• 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.

Exclusion Criteria

• Subjects who have already taken V5 in prior trial and those without baseline data.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Medical University, Ukraine

OTHER

Sponsor Role: collaborator

Immunitor USA Inc.

INDUSTRY

Sponsor Role: collaborator

Lisichansk Regional Tuberculosis Dispensary

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dmytro Butov, MD

Role: PRINCIPAL_INVESTIGATOR

Kharkiv National Medical University

Locations

Lisichansk TB Dispensary

Lisichansk, Luhansk Oblast, Ukraine

Countries

Ukraine

References

DOI 10.2217/imt.12.59

Reference Type: RESULT

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.

Reference Type: DERIVED

PMID: 27868466 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 21182457 (View on PubMed)

Related Links

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

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

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

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

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

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

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

Immune approaches in tuberculosis therapy: a brief overview.

Other Identifiers

imm01

Identifier Type: -

Identifier Source: org_study_id