TuberculosisPhase 2NCT01222338
Safety and Efficacy of Oral Immunomodulator in Tuberculosis (TB) and TB/HIV Patients
A Phase 2 study testing V-5 immunitor in people with Tuberculosis, run by Lisichansk Regional Tuberculosis Dispensary at 1 site in Ukraine.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Tuberculosis
- What is being tested?
- V-5 immunitor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 123 participants
- Where
- 1 siteUkraine
- Study dates
- Jan 2010to Jan 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 24Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 2 Placebo-controlled, Randomized Study of Oral Immunomodulator in TB and TB/HIV Patients
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.
Read the 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
- Being tested
- V-5 immunitor
- Keywords
- Mycobacterium, MDR-TB, XDR-TB, HIV, HCV
- Medical subject headings
- Tuberculosis, Mycobacterium Infections, Tuberculosis, Multidrug-Resistant, Extensively Drug-Resistant Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
V-5 immunitorBiological
Also called V5, V-5 immunitor
once per day dosing for 2 months
| Study group | Role | What they receive |
|---|---|---|
| Immunomodulator intervention | Active comparator | 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. Receives: Biological: V-5 immunitor |
| placebo | Placebo comparator | 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 Receives: Biological: V-5 immunitor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 months
Secondary outcomes (4)
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.
Measured: 12 months
quality of life
Measure changes in quality of life by TB score questionnaire
Measured: 12 months
hematology parameters
Measure CBC by standard routine methods
Measured: 12 months
weight gain
Measure changes in body weight
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2010 (estimated)
- Study startJan 2010
- Primary completionDec 2010
- Study completionJan 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lisichansk Regional Tuberculosis Dispensary
- Sponsor type
- University, hospital or other
- Collaborators
- National Medical University, Ukraine, Immunitor USA Inc.
- Responsible party
- Sponsor
- Investigators
- Dmytro Butov, MD, Principal investigator, Kharkiv National Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01222338
- Sponsor's protocol ID
- imm01
- Status last verified
- Aug 2012
- First submitted
- 30 Jun 2010
- Last updated
- 3 Aug 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
DOI 10.2217/imt.12.59
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.
PubMed 27868466Arjanova 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.
PubMed 21182457
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Placebo-controlled, Randomized Study of Oral Immunomodulator in TB and TB/HIV Patients
- ClinicalTrials.gov ID
- NCT01222338
- Acronym / sponsor ID
- imm01
- Conditions
- Tuberculosis
- Keywords
- Mycobacterium, MDR-TB, XDR-TB, HIV, HCV
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 123 participants (actual)
- Lead sponsor
- Lisichansk Regional Tuberculosis DispensaryUniversity, hospital or other
- Collaborators
- National Medical University, Ukraine, Immunitor USA Inc.
- Study start
- Jan 2010
- Primary completion
- Dec 2010 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 18 Oct 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immunomodulator intervention | Active comparator | Biological: V-5 immunitorTwo 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. |
| placebo | Placebo comparator | Biological: V-5 immunitorControl 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 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (24 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| V-5 immunitorAlso: V5, V-5 immunitoronce per day dosing for 2 months | Biological | Immunomodulator intervention, placebo |
Primary outcome
primary endpoint: sputum smear conversion
Time frame: 12 months
Sputum smear conversion at monthly intervals timepoint Rates of pulmonary healing by chest X-ray at the end of study
4 secondary outcomes
liver function
Time frame: 12 months
quality of life
Time frame: 12 months
hematology parameters
Time frame: 12 months
weight gain
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2012.
- Results publicationDOI 10.2217/imt.12.59
- Derived from this study: PubMed 27868466Batbold 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.
- Derived from this study: PubMed 21182457Arjanova 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.
- Phase 2 trial of V-5 Immunitor (V5) in patients with chronic hepatitis C co-infected with HIV and Mycobacterium tuberculosisLink provided by the sponsor.
- doi: 10.4172/2161-1068.S1-001 Therapeutic Vaccination of Treatment-Failed TB Patients on "Palliative" Support Consisting of Isoniazid and RifampicinLink provided by the sponsor.
- Phase IIb randomized trial of adjunct immunotherapy in patients with first-diagnosed tuberculosis, relapsed and multi-drug-resistant (MDR) TB.Link provided by the sponsor.
- Immune approaches in tuberculosis therapy: a brief overview.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dmytro Butov, MD principal investigator
Kharkiv National Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing V-5 immunitor in people with Tuberculosis, run by Lisichansk Regional Tuberculosis Dispensary at 1 site in Ukraine.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Ukraine. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
primary endpoint: sputum smear conversion (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01222338, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Aug 2012.