Study on the Use of Interferon Gamma (Ingaron) Injections in Patients With Drug-resistant Pulmonary Tuberculosis

An Open Prospective Observational Study Evaluating the Efficacy and Tolerability of Interferon Gamma (Ingaron) Injections in Patients With Drug-resistant Pulmonary Tuberculosis

The purpose of this study is to evaluate the efficacy and tolerability of the complex therapy of drug-resistant respiratory tuberculosis using the drug Ingaron, a lyophilisate for the preparation of a solution for injection for intramuscular or subcutaneous administration of 500,000 IU.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Tuberculosis
• Intervention / Treatment: Drug: Interferon-Gamma

Detailed Description

Open prospective observational cohort study. During the recruitment phase, a preliminary assessment of eligibility and non-inclusion criteria will be carried out.

Subject to prior compliance with all inclusion criteria and none of the exclusion criteria, after signing a voluntary informed consent, the patient will be included in the study.

Patients will be divided into groups, depending on the therapy prescribed to them as part of routine clinical practice (according to clinical guidelines):

Group 1:

Pathogenetic therapy with the use of the drug Ingaron + basic anti-tuberculosis therapy in accordance with approved clinical guidelines.

Group 2:

Basic anti-tuberculosis therapy in accordance with approved clinical guidelines.

When a patient is included in the study (Visit 0), an initial examination will be carried out, in accordance with generally accepted principles of treatment monitoring, which includes: history taking, physical examination, registration of vital signs, ECG, blood samples for general clinical, biochemical analysis, general analysis urine, bacteriological examination by sputum smear microscopy and sputum culture on dense nutrient media with drug sensitivity assessment, computed tomography and chest radiography.

The inclusion/exclusion criteria will be checked. The expected duration of the study for each patient will be no more than 204 days.

After the start of therapy, patients will be recorded monthly with physical examination data with registration of vital signs, general clinical, biochemical analyzes, urinalysis, smear microscopy and sputum culture. X-ray examination and clinical evaluation of effectiveness will be carried out every 2 months. At visit 7 (after 6 months from the start of therapy), an evaluation of computed tomography and chest x-ray in dynamics with an assessment of the effectiveness of therapy, as well as ECG, physical examination with registration of vital signs, general clinical, biochemical analyzes, general urinalysis, smear microscopy and culture of sputum.

At visits 1, 4 and 7 immunological parameters will be assessed.

• Study Type: Observational
• Enrollment (Anticipated): 84

Contacts and Locations

• Study Contact: Name: Julia A Isakova, Master; Phone Number: 8 107 905 535-33-11; Email: isakova@pharmaclon.ru
• Study Contact Backup: Name: Polina I Pekhtereva, Master; Phone Number: 8 107 909 675-96-43; Email: pekhtereva@pharmaclon.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 127473
    • Recruiting
    • FSBI "NMIC FPI" of the Ministry of Health of Russia
    • Contact: Anastasia G Samoilova, Dr. med.; Phone Number: 8107 (495) 631-15-15; Email: a.samoilova.nmrc@mail.ru
    • Contact: Dar'ja P Korneva, Master; Phone Number: 5004 8107 (495) 631-15-15; Email: kornevadp@nmrc.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

patients with drug-resistant pulmonary tuberculosis with bacterial excretion

Description

Inclusion Criteria:

• Men or non-pregnant women 18-75 years of age.
• For women of childbearing age who are fertile: Agree to completely abstain from sexual intercourse or use dual methods of contraception to prevent pregnancy while participating in the study.
• Verified diagnosis of pulmonary tuberculosis (infiltrative tuberculosis, fibrous-cavernous tuberculosis in the infiltration phase).
• A positive sputum smear microscopy test result for acid-fast bacterium, assessed as moderate (++) or massive bacterial excretion (+++) no earlier than 30 days prior to enrollment in the study.
• Established resistance of the isolated pathogen to at least rifampicin, determined by molecular genetic or cultural methods for determining drug susceptibility.
• Prescribing the current baseline chemotherapy regimen according to clinical guidelines no earlier than 14 days prior to enrollment in the study.
• Compliance with prescribed therapy.
• No concomitant immunotherapy, or 6 months from the last dose of an immunomodulatory drug to the start of therapy.
• Absence of comorbidities and therapy that may affect the interpretation of study results, in the opinion of the investigator.
• Signed written informed consent to participate in the study.
• Willingness and ability to follow protocol requirements throughout the study.

Exclusion Criteria:

• For women: pregnant, breastfeeding or planning a pregnancy during the study period.
• Caseous pneumonia.
• Asthma, with the exception of mild intermittent asthma.
• Systemic fungal infections.
• Use of any investigational drug within 30 days prior to screening.
• Oncological diseases (cytotoxic chemotherapy, current or received within the last 3 months before the start of treatment).
• Chronic diseases of the liver or kidneys (an increase in liver transaminases more than 5 times the upper limit of laboratory norms for these indicators; an increase in creatinine above 2 mg / 100 ml (or μmol / l)).
• Diabetes.
• HIV infection or other immunodeficiency conditions.
• Inability, in the opinion of the investigator, to comply with the treatment regimen and the requirements of the study protocol.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Experimental; Ingaron + basic TB therapy 500,000 IU once daily for 3 months followed by 3 months follow-up	Drug: Interferon-Gamma; received by microbiological synthesis; specific antiviral activity on cells is 2x10*7 Units per mg of protein; Other Names: Ingaron; Interferon gamma human recombinant
No Intervention; only basic anti-tuberculosis therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sputum smear conversion according to microscopy.	Sputum smear conversion according to microscopy. Percentage of patients.	1 months
Sputum smear conversion according to microscopy.	Sputum smear conversion according to microscopy. Mean time to clinical response.	1 months
Sputum smear conversion according to microscopy.	Sputum smear conversion according to microscopy. Percentage of patients.	2 months
Sputum smear conversion according to microscopy.	Sputum smear conversion according to microscopy. Mean time to clinical response.	2 months
Sputum smear conversion according to microscopy.	Sputum smear conversion according to microscopy. Percentage of patients.	3 months
Sputum smear conversion according to microscopy.	Sputum smear conversion according to microscopy. Mean time to clinical response.	3 months
Sputum smear conversion according to microscopy.	Sputum smear conversion according to microscopy. Percentage of patients.	4 months
Sputum smear conversion according to microscopy.	Sputum smear conversion according to microscopy. Mean time to clinical response.	4 months
Sputum smear conversion according to microscopy.	Sputum smear conversion according to microscopy. Percentage of patients.	5 months
Sputum smear conversion according to microscopy.	Sputum smear conversion according to microscopy. Mean time to clinical response.	5 months
Sputum smear conversion according to microscopy.	Sputum smear conversion according to microscopy. Percentage of patients.	6 months
Sputum smear conversion according to microscopy.	Sputum smear conversion according to microscopy. Mean time to clinical response.	6 months
Sputum smear conversion by culture.	Sputum smear conversion by culture. Percentage of patients.	1 months
Sputum smear conversion by culture.	Sputum smear conversion by culture. Mean time to clinical response.	1 months
Sputum smear conversion by culture.	Sputum smear conversion by culture. Percentage of patients.	2 months
Sputum smear conversion by culture.	Sputum smear conversion by culture. Mean time to clinical response.	2 months
Sputum smear conversion by culture.	Sputum smear conversion by culture. Percentage of patients.	3 months
Sputum smear conversion by culture.	Sputum smear conversion by culture. Mean time to clinical response.	3 months
Sputum smear conversion by culture.	Sputum smear conversion by culture. Percentage of patients.	4 months
Sputum smear conversion by culture.	Sputum smear conversion by culture. Mean time to clinical response.	4 months
Sputum smear conversion by culture.	Sputum smear conversion by culture. Percentage of patients.	5 months
Sputum smear conversion by culture.	Sputum smear conversion by culture. Mean time to clinical response.	5 months
Sputum smear conversion by culture.	Sputum smear conversion by culture. Percentage of patients.	6 months
Sputum smear conversion by culture.	Sputum smear conversion by culture. Mean time to clinical response.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effectiveness of therapy according to X-ray examination of the chest.	The effectiveness of therapy according to X-ray examination of the chest. Percentage of patients.	2 months
The effectiveness of therapy according to X-ray examination of the chest.	The effectiveness of therapy according to X-ray examination of the chest. Percentage of patients.	4 months
The effectiveness of therapy according to X-ray examination of the chest.	The effectiveness of therapy according to X-ray examination of the chest. Percentage of patients.	6 months
The effectiveness of therapy according to computed tomography of the chest.	The effectiveness of therapy according to computed tomography of the chest. Percentage of patients.	6 months
The effectiveness of therapy according to clinical examination.	The effectiveness of therapy according to clinical examination. Average score. The dynamics of clinical symptoms will be determined based on an assessment of the severity of intoxication (general) symptoms and respiratory complaints according to a 4-point system, where the minimum score is 0 - absent, the maximum 3 - pronounced	2 months
The effectiveness of therapy according to clinical examination.	The effectiveness of therapy according to clinical examination. Average score. The dynamics of clinical symptoms will be determined based on an assessment of the severity of intoxication (general) symptoms and respiratory complaints according to a 4-point system, where the minimum score is 0 - absent, the maximum 3 - pronounced	4 months
The effectiveness of therapy according to clinical examination.	The effectiveness of therapy according to clinical examination. Average score. The dynamics of clinical symptoms will be determined based on an assessment of the severity of intoxication (general) symptoms and respiratory complaints according to a 4-point system, where the minimum score is 0 - absent, the maximum 3 - pronounced	6 months
Change in immunological status (CD4 and CD8 lymphocyte populations) compared with baseline values (before therapy).	Change in immunological status (CD4 and CD8 lymphocyte populations) compared with baseline values (before therapy). Averages.	3 months
Change in immunological status (CD4 and CD8 lymphocyte populations) compared with baseline values (before therapy).	Change in immunological status (CD4 and CD8 lymphocyte populations) compared with baseline values (before therapy). Averages.	6 months
Mortality rate.	Mortality rate. The proportion of patients.	6 months

Collaborators and Investigators

• Sponsor: SPP Pharmaclon Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 15, 2022
• Primary Completion (ANTICIPATED): August 1, 2022
• Study Completion (ANTICIPATED): May 1, 2023

Study Registration Dates

• First Submitted: April 22, 2022
• First Submitted That Met QC Criteria: April 27, 2022
• First Posted (ACTUAL): May 3, 2022

Study Record Updates

• Last Update Posted (ACTUAL): June 1, 2022
• Last Update Submitted That Met QC Criteria: May 31, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: interferon gamma; drug resistant; treatment of drug-resistant pulmonary tuberculosis
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Interferons; Interferon-gamma
• Other Study ID Numbers: STING-2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No