Clinical trial NCT06440746: Efficacy and Safety of Olokizumab in Patients With Progressive Fibrosing Interstitial Lung Diseases
Official title: A Randomized, Double-blind, Parallel-group, Placebo-controlled, Multicenter Phase 2/3 Study of Efficacy and Safety of Olokizumab in Subjects With Progressive Fibrosing Interstitial Lung Diseases
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Lung Diseases, Interstitial
Keywords: Progressive Fibrosing Interstitial Lung Diseases
Olokizumab
Forced vital capacity
Lead sponsor: R-Pharm
Sponsor class: INDUSTRY
Collaborators: name: R-Pharm
name: Exacte Labs LLC
name: Data Management 365
name: Keystat, LLC
First posted: 2024-06-04
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate efficacy and safety of olokizumab (OKZ) compared to placebo in patients progressive fibrosing Interstitial lung diseases (ILD).

Detailed description: This is a phase 2/3 study with double-blind parallel-group adaptive design.

The study will include the following periods:

1. Screening period (4 weeks) Screening period (before the first administration of the test drug). Before being included in the study, patients will be provided with complete information about this clinical trial and signs the Informed consent Form (IF). After that the researcher will decide whether or not the patient can be randomized into the study.
2. Double-blind Treatment period (48 weeks). Following the completion of a Treatment period, all patients will be enrolled in Follow-up Period (FU).
3. Follow-up Period (24 weeks). During the FU Period, patients will visit study sites after 4,12 and 24 weeks after the end of the Treatment Period to complete FU-1 (Week 52), FU-2 (Week 60) and FU-3 (Week 72) visits.

The overall study duration for the patients will be approximately 76 weeks (including the 4 weeks screening period)

The analysis will be conducted in two sequential steps:

* the interim analysis after 61 percent (%) of patients have completed the Treatment period (not including the FU period)
* the final analysis when all patients have completed all periods (the Treatment and the FU periods).

Eligibility criteria: Inclusion Criteria:

1. The patient has signed the Informed Consent Form
2. Progressive fibrosing ILD confirmed by high-resolution computed tomography (HRCT) documented evidence of \>10% lung tissue affected at Screening:

   A. Patients with an usual interstitial pneumonia (UIP) -like radiological pattern described in the 2022 American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines for the management Idiopathic pulmonary fibrosis (IPF) that do not have an identified primary condition

   В. Patients with progressive interstitial pneumonia with autoimmune features (IPAF) as defined in the American Thoracic Society/European Respiratory Society Statement, 2015

   С. Patients with progressive lung fibrosis associated with different disorders (c) such as systemic connective tissue diseases, chronic fibrosin hypersensitivity pneumonitis (HP), idiopathic non-specific interstitial pneumonia (iNSIP) or sarcoidosis.

   Disease progression will be established based on a combination of criterion (I)(a) and criterion (II) or criterion (III)(b)

   I. Clinically significant decrease in FVC% predicted defined as absolute decrease of ≥ 5% within 12 months prior to screening or an absolute decrease DLCO (corrected for hemoglobin) of ≥10% predicted within 12 months prior to screening.

   II. Worsening respiratory symptoms without an alternative explanation within 12 months prior to screening.

   III. Increased area affected with fibrosis on chest HRCT (b) (according to the 2022 American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association guidelines) within 24 months prior to screening.
   1. To assess this criterion (I), patient's pulmonary function test (PFT) results obtained within 12 months prior to screening must available. If data from multiple PFTs are available, the earliest results must be used for assessment.
   2. Patients' results of at least one chest HRCT investigation performed no earlier than 24 months before randomization must be available for review. If results of multiple HRCT examinations are available, patient eligibility must be based on the earliest results.
   3. stable course of the main disease not requiring a change in maintenance treatment.
3. ILD duration of no more than 8 years from the onset of respiratory symptoms by the date screening begins.
4. Elevated acute phase reactants at screening not related to other causes:

   C-reactive protein level ≥6 mg/l or Erythrocyte Sedimentation Rate (ESR) ≥28 millimeters per hour (mm/hour).
5. FVC ≥ 45% and ≤ 80% predicted at screening.

Non-Inclusion Criteria:

1. Hemoglobin-corrected DLCO \< 30% predicted at screening.
2. Significant airway obstruction at screening defined as a Forced expiratory volume in 1 second (FEV1) / FVC ratio of \<70 %.
3. Use of interleukin-6(IL-6 )inhibitors or IL-6 receptor inhibitors except for CoronaVirus Disease2019 (COVID-19) treatment. If those medications are used to treat COVID-19, the last administration of IL-6 inhibitors or IL-6 receptor inhibitors must have occurred at least 6 months prior to screening.
4. Administration of rituximab within less than 12 months prior to screening.
5. Treatment with systemic glucocorticosteroids (GCS) at \>10 mg/day calculated for prednisolone; or a change in the dose of GCS within 4 weeks before/during the screening period; or planned dose changes during the trial.
6. A history of bone marrow transplantation, total lymphoid tissue irradiation, or administration of ablative ultra-high doses of cyclophosphamide.
7. Initiation of mycophenolate mofetil or antifibrotic agents (for patients receiving mycophenolate mofetil and/or antifibrotics at study entry) less than 12 months prior to screening.

   • If a patient has been taking antifibrotic drugs for \<12 months and ≥6 months, and the spirometry/Diffusion Capacity Of The Lungs For Carbon Monoxide (DLCO) used to assess progression was performed within ±2 weeks of actually starting antifibrotic drugs, the patient may be included in the study
8. Discontinuation of previously prescribed antifibrotic agents within 6 months prior to screening (for patients not receiving antifibrotic drugs at study entry).
9. Participation in any other clinical trial less than 30 days prior to the baseline assessment or less than 5 half-lives of the medication examined in another clinical trial, whichever is longer.
10. Laboratory abnormalities as follows:

    * Alanine Aminotransferase (ALT) or Aspartate Aminotransferase(AST) ≥ 1.5×Upper Limit Normal (ULN)
    * Platelet count \<100×10\^9/litre (l) (\<100000/cubic millimetre (mm\^3)
    * Leukocyte count \<3.5×10\^9/l
    * Absolute neutrophil count \<2000×10\^6/l (\<2000/mm\^3).
11. Concurrent malignancy or a history of malignancy within the last 5 years.
12. Any acute infection at screening or exacerbation of a chronic infection, any infection requiring oral antibiotics or antivirals within 4 weeks prior to screening, injection of antimicrobial agents within 6 weeks before randomization, severe or recurrent infections requiring hospital admission within 6 months before randomization.
13. Patients with evidence of disseminated herpes zoster infection, herpes zoster with encephalitis, meningitis, or other forms of herpes zoster infection that do not resolve without treatment and occurred within 6 months prior to screening.
14. Evidence of any other chronic infection (including sepsis, invasive fungal infection, histoplasmosis, osteomyelitis) which, in the opinion of the Investigator, may increase the risk of infectious complications during the trial.
15. Patients with diverticulitis or other symptomatic gastrointestinal diseases that may lead to perforation, including such history (for example, diverticulitis, gastrointestinal perforation, ulcerative colitis).
16. Women of child-bearing potential or men whose partners are women of child-bearing potential who do not want to use highly effective methods of contraception during the trial and for at least 3 months after the last administration of the investigational product.
17. Known hypersensitivity to OKZ or any other component of the product or placebo.
18. History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies.
19. Other protocol-defined non-inclusion criteria apply.

Primary outcomes:
measure: The rate of forced vital capacity (FVC)
timeFrame: 48 weeks
Secondary outcomes:
measure: Change in FVC from baseline
timeFrame: 24, 48 weeks.
measure: Change in FVC.% predicted
timeFrame: 24,48 weeks
measure: Number of patients (in %) with a decrease in FVC
timeFrame: 48 weeks
measure: Number of patients (in %) with improved pulmonary function
timeFrame: 48 weeks
measure: Change of Diffusing capacity of the lungs for carbon monoxide (DLCO)
timeFrame: 24,48 weeks
measure: Change in the values of quantitative assessment of lung fibrosis from baseline
timeFrame: 48 weeks
measure: Proportion of patients with progression or death
timeFrame: 48 weeks
measure: Time to progression or death assessed over 48 weeks of treatment
timeFrame: 48 weeks
measure: Time to exacerbation over 48 weeks of treatment
timeFrame: 48 weeks
measure: Proportion of patients with exacerbation at treatment weeks 24 and 48
timeFrame: 24,48 weeks
measure: Change in Functional Assessment of Chronic Illness Therapy (FACIT)-Dyspnea scores from baseline at treatment weeks 24 and 48
timeFrame: 24,48 weeks
measure: Change in Short Form-36 (SF-36) scores from baseline at treatment weeks 24 and 48
timeFrame: 24,48 weeks
measure: Change in Modified Medical Research Council ( mMRC) dyspnea score from baseline at treatment weeks 24 and 48
timeFrame: 24,48 weeks
Other outcomes:
Locations:
city: Barnaul
country: Russian Federation
facility: Regional Clinical Hospital Regional state budgetary healthcare institution
city: Chelyabinsk
country: Russian Federation
facility: Regional Clinic Hospital№3
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Hospital
city: Ekaterinburg
country: Russian Federation
facility: Ural research Institute of Phthisiopulmonology
city: Gatchina
country: Russian Federation
facility: State budgetary healthcare institution of the Leningrad region "Gatchina Clinical Interdistrict Hospital"
city: Izhevsk
country: Russian Federation
facility: LLC" Medsi-Izhevsk"
city: Kazan
country: Russian Federation
facility: LLC "Scientific Research Medical Complex "Your Health"
city: Kemerovo
country: Russian Federation
facility: Kuzbass Clinical Hospital Emergency Medical Care named after Podgorbunsky M.A
city: Krasnodar
country: Russian Federation
facility: State Budgetary Healthcare Institution Research Institute-Karpaty Clinical Hospital No. 1 named after prof. S.V. Ochapovsky
city: Moscow
country: Russian Federation
facility: City Clinical Hospital named after Davydovsky I.V.
city: Moscow
country: Russian Federation
facility: GBUZ Moscow Clinical Scientific Center named after Loginov MHD
city: Moscow
country: Russian Federation
facility: Scientific Research Institute of Reumatology named after Nasonova V.A
city: Moscow
country: Russian Federation
facility: Moscow City Polyclinic №52
city: Moscow
country: Russian Federation
facility: Clinical Hospital №4 of Sechenov University
city: Moscow
country: Russian Federation
facility: Clinical Hospital №3 of Sechenov University
city: Moscow
country: Russian Federation
facility: State Budgetary Healthcare Institution of Moscow City "City Clinical Hospital №52" of the Moscow City Health Department", Consultative and diagnostic department №2
city: Moscow
country: Russian Federation
facility: State Budgetary Healthcare Institution of Moscow City "City Clinical Hospital №52" of the Moscow City Health Department"
city: Moscow
country: Russian Federation
facility: FSBEI HE "Russian University of Medicine", MoH of Russia
city: Moscow
country: Russian Federation
facility: Moscow Regional Research and Clinical Institute "MONIKI"
city: Novosibirsk
country: Russian Federation
facility: Federal Research Center Institute of Cytologyand Genetics,Siberian Branch of Russian Academy of Sciences
city: Petrozavodsk
country: Russian Federation
facility: Republican Hospital named after V.A. Baranov
city: Saint Petersburg
country: Russian Federation
facility: Saint-Petersburg State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian Federation
city: Saint Petersburg
country: Russian Federation
facility: LLC"Energy of Health"
city: Saint Petersburg
country: Russian Federation
facility: Medical Center "Interleukin"
city: Saint Petersburg
country: Russian Federation
facility: City Multidisciplinary Hospital №2-Expert Center in the field of Pulmonology
city: Saint Petersburg
country: Russian Federation
facility: LLC"Kurator"
city: Saratov
country: Russian Federation
facility: State Healthcare Institution "Regional Clinical Hospital"
city: Smolensk
country: Russian Federation
facility: Regional state budgetary healthcare institution "Clinical Hospital No. 1"
city: Tomsk
country: Russian Federation
facility: Regional State Budgetary Healthcare Institution "Medical and Sanitary Unit No. 2
city: Ufa
country: Russian Federation
facility: Federal State Budgetary Educational Institution of Higher Education "Bashkir State Medical University" of the Ministry of Health of the Russian Federation
city: Vladimir
country: Russian Federation
facility: State Budgetary Healthcare Institution of the Vladimir Region "Regional Clinical Hospital"
city: Voronezh
country: Russian Federation
facility: Budgetary healthcare institution of the Voronezh region "Voronezh Regional Clinical Hospital No1"
city: Yaroslavl
country: Russian Federation
facility: Clinical Hospital of Emergency Medical Care named after Solovyov N.V
Study officials:
affiliation: R-Pharm
name: Mikhail Samsonov
role: STUDY_DIRECTOR
References: