HIV Coinfection, Aids/Hiv Problem, Tuberculosis, Pulmonary, Human Immunodeficiency Virus, Lentivirus Infections, RNA Virus Infections
Conditions
Keywords
interferon gamma, IFN-g, HIV infection, tuberculosis
Brief summary
The primary purpose of this study is to assess the safety and efficacy of interferon-gamma by subcutaneous injection in complex treatment of patients with co-infection of HIV and pulmonary tuberculosis and to determine the rational of its use.
Detailed description
Study will evaluate safety and efficacy of the investigational medical product (IMP) - interferon-gamma - in participants with HIV-infection and pulmonary tuberculosis. Interferon-gamma (immune interferon) is an important anti-inflammatory cytokine produced by NK-cells, CD4 Th1 cells and CD8 cytotoxic supressor cells. Interferon-gamma blocks viral replication, viral proteins synthesis and assembly of mature viral particles. Causes cytotoxic effects on the cells infected by intracellular pathogens. Possess a bright immunomoduling action. Thus, the use of interferon-gamma is patogenetically rational in patients co-infected with tuberculosis and HIV. The aim of interferon-gamma use is to achieve a viral replication control, support CD4 level and help abacillation process. In this randomised, controlled safety and efficacy study interferon gamma will be administered in a daily dose of 500,000 IU daily or every other day. The treatment regimen in this study will also include a basic antituberculosis therapy. The available clinical data do not suggest a risk for serious adverse events (SAEs) from the IMP used in chosen doses. The study will screen HIV-infected participants 18-50 years old with pulmonary tuberculosis. Participants who provide informed consent and meet study entry criteria will be randomised into 1 of 3 parallel treatment groups. The study will last 30 days, during which participants will receive IMP in various regimens according to the group.
Interventions
DRUGInterferon-Gamma
received by microbiological synthesis; specific antiviral activity on cells is 2x10\*7 Units per mg of protein
Sponsors
North-Western State Medical University named after I.I.Mechnikov
SPP Pharmaclon Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Participants must sign the form of informed consent and agree to follow the protocol requirements * Women willing to participate in the study must protect against possible pregnancy during all the study long * Age 18-50 years * Pulmonary tuberculosis * HIV/AIDS * Indication for in-patient standard antituberculosis treatment
Exclusion criteria
* Investigational research agents received within 30 days before the screening and participation in other clinical trials * Immunosuppressive medications received within 6 months before the screening * Current drug abuse for more than 3 years * Contraindications to interferons of standard antimicrobial therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sputum Culture | Week 4 | Precentage of participants with negative sputum culture |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Leucocytes Level | Screening, Week 4 | Number of leukocytes |
| CD3 | Screening, Week 4 | CD3 cells level in absolute numbers and percents |
| Average Hemoglobin Level | Screening, Week 8 | Level of hemoglobin (g/L) |
| CD8 | Screening, Week 4 | CD8 cells level in absolute numbers and percents |
| CD4/CD8 | Screening, Week 4 | Immunoregulatory index value |
| CD4 | Screening, Week 4 | CD4 cells level in absolute numbers and percents |
Countries
Russia
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Interferon All participants receive subcutaneous interferon-gamma (Ingaron®) 500,000 IU alternated with Interal® (interferon alpha) 3,000,000 IU every other day
Interventions:
Drug: Ingaron® Drug: Interal® Drug: Antituberculosis complex therapy
Interferon-Gamma: received by microbiological synthesis; specific antiviral activity on cells is 2x10\*7 Units per mg of protein | 30 |
| Interferon Daily All participants receive subcutaneous interferon-gamma (Ingaron®) 500,000 IU given with Interal® (interferon alpha) 3,000,000 IU every day
Interventions:
Drug: Ingaron® Drug: Interal® Drug: Antituberculosis complex therapy
Interferon-Gamma: received by microbiological synthesis; specific antiviral activity on cells is 2x10\*7 Units per mg of protein | 28 |
| Control All participants receive only basic antimicrobial treatment
Interventions:
Drug: Antituberculosis complex therapy | 20 |
| Total | 78 |
Baseline characteristics
| Characteristic | Interferon | Total | Control | Interferon Daily |
|---|---|---|---|---|
| Age, Customized 18-50 y.o. | 30 Participants | 78 Participants | 20 Participants | 28 Participants |
| Age, Customized over 50 y.o. | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized under 18 y.o. | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Russia | 30 participants | 0 participants | 20 participants | 28 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 30 Participants | 78 Participants | 20 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 28 | 0 / 20 |
| other Total, other adverse events | 0 / 30 | 0 / 28 | 0 / 20 |
| serious Total, serious adverse events | 0 / 30 | 0 / 28 | 0 / 20 |
Outcome results
Primary
Sputum Culture
Precentage of participants with negative sputum culture
Time frame: Week 4
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Interferon | Sputum Culture | 15 Participants |
| Interferon Daily | Sputum Culture | 20 Participants |
| Control | Sputum Culture | 14 Participants |
Secondary
Average Hemoglobin Level
Level of hemoglobin (g/L)
Time frame: Screening, Week 8
Secondary
CD3
CD3 cells level in absolute numbers and percents
Time frame: Screening, Week 4
Secondary
CD4
CD4 cells level in absolute numbers and percents
Time frame: Screening, Week 4
Secondary
CD4/CD8
Immunoregulatory index value
Time frame: Screening, Week 4
Secondary
CD8
CD8 cells level in absolute numbers and percents
Time frame: Screening, Week 4
Secondary
Leucocytes Level
Number of leukocytes
Time frame: Screening, Week 4