Clinical trial NCT05785624: A Study Evaluating the Efficacy and Safety of Vixarelimab in Participants With Idiopathic Pulmonary Fibrosis and in Participants With Systemic Sclerosis-Associated Interstitial Lung Disease
Official title: A Two-Cohort, Phase II, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study Evaluating the Efficacy and Safety of Vixarelimab Compared With Placebo in Patients With Idiopathic Pulmonary Fibrosis and in Patients With Systemic Sclerosis-Associated Interstitial Lung Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Systemic Sclerosis With Lung Involvement
Keywords: Systemic Sclerosis-Associated Interstitial Lung Disease
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2023-03-27
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of the study is to evaluate the efficacy of vixarelimab compared with placebo on lung function in participants with idiopathic pulmonary fibrosis (IPF) and in participants with systemic sclerosis-associated interstitial lung disease (SSc-ILD). Participants who complete 52-weeks of treatment in the Double-blind Treatment (DBT) period can choose to enroll in the optional Open-label Extension (OLE) period to receive treatment with vixarelimab for another 52 weeks.

Cohort 1 has completed enrollment and has been closed for further enrollment. Cohort 2 is enrolling participants.


Eligibility criteria: Inclusion Criteria for all Participants:

* FVC ≥45% predicted during screening as determined by the over-reader
* Forced expiratory volume in 1 second (FEV1)/FVC ratio \>0.70 during screening as determined by the over-reader
* DLco ≥30% and ≤90% of predicted during screening (Hgb corrected) as determined by the over-reader
* Minimum 6-MWT distance of 150 m with maximum use of 6 liters per minute (L/min) at sea-level and up to 8 L/min at altitude (\> 5000 feet \[1524 m\] above sea level) of supplemental oxygen while maintaining oxygen saturation of \>83% during the 6MWT during screening
* Participant and investigator consideration of all medicinal treatment options and/or possibly lung transplantation prior to consideration of participation in the study

Inclusion Criteria for Cohort 1:

* Age 40-85 years
* Documented diagnosis of IPF or IPF (likely)
* HRCT pattern consistent with the diagnosis of IPF, confirmed by central review of chest HRCT and central review of any available lung biopsy
* For participants receiving pirfenidone or nintedanib treatment for IPF: treatment for ≥3 months with a stable dose for ≥4 weeks prior to screening and during screening, with plans to continue treatment during the study period

Inclusion Criteria for Cohort 2:

* Age 18-85 years
* Diagnosis of SSc as defined using the American College of Rheumatology/European Alliance of Associations for Rheumatology (EULAR) criteria
* HRCT demonstrating ≥10% extent of fibrosis, confirmed by central review of Chest HRCT
* Evidence of progression of pulmonary fibrosis
* For participants receiving tocilizumab treatment for SSc-ILD: treatment for ≥3 months with a stable dose for ≥4 weeks prior to screening and during screening, with no contraindications according to local prescribing information, and no intention to change or modify their treatment regimen for the duration of the study
* For participants receiving nintedanib treatment for SSc-ILD: treatment for ≥ 3 months with a stable dose for ≥ 4 weeks prior to screening and during screening, with no contraindications according to local prescribing information, and no intention to change or modify their treatment regimen for the duration of the study
* Availability of skin for biopsy preferably on proximal forearms having Modified Rodnan Skin Score (mRSS) ≥2 at the biopsy location

Inclusion Criteria for OLE Period:

* Completion of 52 weeks of treatment in the double-blinded treatment period
* Investigator determination of a favorable benefit-risk for the individual participant, i.e., the expectation of reasonable likelihood for therapeutic benefit and tolerability of the study drug after evaluation of the preceding 52 weeks of double-blinded treatment

Exclusion Criteria for all Participants:

* Percentage of predicted FVC value showing improvement in the 6-month period prior to screening and including screening value
* Known post-bronchodilator response in FEV1 and/or FVC (defined as an increase in percent predicted values by ≥ 10)
* Resting oxygen saturation of \<89% using up to 4 L/min of supplemental oxygen at sea level and up to 6 L/min at altitude (5000 feet \[1524 m\] above sea level) during screening
* History of lung transplant
* Previous treatment with vixarelimab
* Acute respiratory or systemic bacterial, viral, or fungal infection either during screening or prior to screening not successfully resolved by 4 weeks prior to screening visit
* Presence of pulmonary hypertension requiring treatment
* History of malignancy within the 5 years prior to screening
* Positive hepatitis C virus (HCV) antibody test result accompanied by a positive HCV ribonucleic acid (RNA) test at screening
* Known immunodeficiency
* Known evidence of active or untreated latent tuberculosis

Exclusion Criteria for Cohort 1:

* Evidence of other known causes of ILD
* Emphysema present on ≥50% of the HRCT, or the extent of emphysema is greater than the extent of fibrosis, according to central review of the HRCT

Exclusion Criteria for Cohort 2:

* Evidence of other known causes of ILD
* Rheumatic autoimmune disease other than SSc
* Receiving pirfenidone treatment within 4 weeks prior to screening
* Receipt of nintedanib in combination with tocilizumab

Exclusion Criteria for OLE Period:

* Significant non-compliance in the double-blinded treatment period, per investigator's judgment
* Any new clinically significant pulmonary disease other than IPF or SSc-ILD since enrolling in the double-blinded treatment period

Primary outcomes:
measure: Cohorts 1 and 2: Absolute Change From Baseline in Forced Vital Capacity (FVC)
timeFrame: Baseline up to Week 52
Secondary outcomes:
measure: Cohorts 1 and 2: Absolute Change From Baseline in 6-Minute Walk Test (6MWT) Distance
timeFrame: Baseline up to Week 52
measure: Cohorts 1 and 2: Absolute Change From Baseline in Percentage of Predicted FVC
timeFrame: Baseline up to Week 52
measure: Cohorts 1 and 2: Change From Baseline in Diffusion Capacity of the Lung for Carbon Monoxide Adjusted for Hemoglobin (DLco [Hb])
timeFrame: Baseline up to Week 52
measure: Cohorts 1 and 2: Time to Disease Progression
timeFrame: From the start of study treatment until disease progression or death, whichever occurs first (up to Week 52 of DBT)
measure: Cohorts 1 and 2: Time to First Acute Exacerbation of ILD, or Suspected Acute Exacerbation of ILD
timeFrame: From the start of study treatment until end of DBT (up to Week 52)
measure: Cohorts 1 and 2: Change From Baseline in Quantitative Lung Fibrosis on High-Resolution Computed Tomography (HRCT) Scan of the Thorax
timeFrame: Baseline up to Week 52
measure: Cohorts 1 and 2: Percentage of Participants with Deaths
timeFrame: Up to Week 52
measure: Cohort 2: Change From Baseline in Skin Sclerosis Assessed Using Modified Rodnan Skin Score (mRSS)
timeFrame: Baseline up to Week 52
measure: Cohorts 1 and 2: Change From Baseline in Health-Related Quality of Life (HRQoL) Measured Using King's Brief Interstitial Lung Disease (K-BILD) Questionnaire
timeFrame: Baseline up to Week 52
measure: Cohorts 1 and 2: Change From Baseline in Cough Measured Using Living with Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score
timeFrame: Baseline up to Week 52
measure: Cohorts 1 and 2: Change From Baseline in Dyspnea Measured Using L-PF Symptoms Dyspnea Domain Score
timeFrame: Baseline up to Week 52
measure: Cohort 2: Change From Baseline in Pruritus Measured Using the Five-Dimension Itch Scale (5-D Itch) Total Score
timeFrame: Baseline up to Week 52
measure: Cohorts 1, 2 and OLE Period: Number of Participants With Adverse Events (AEs)
timeFrame: Up to Week 52
measure: Cohorts 1 and 2: Serum Concentration of Vixarelimab
timeFrame: Baseline up to Week 52
measure: Cohorts 1 and 2: Number of Participants With Anti-Drug Antibodies (ADAs) to Vixarelimab
timeFrame: Baseline up to Week 52
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Banner University Medicine Lung Institute
state: Arizona
city: Tucson
country: United States
facility: Southern Arizona VA Health Care System NAVREF PPDS
state: Arizona
city: Fresno
country: United States
facility: University of California, San Francisco-Fresno
state: California
city: Los Angeles
country: United States
facility: University of Southern California Keck School of Medicine
state: California
city: Los Angeles
country: United States
facility: UCLA Rheumatology
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco Medical Center
state: California
city: Torrance
country: United States
facility: The Lundquist Institute for BioMedical Innovation at Harbor-UCLA Medical Cente
state: California
city: Ocala
country: United States
facility: Renstar Medical Research
state: Florida
city: Orlando
country: United States
facility: Central Florida Pulmonary Group, PA
state: Florida
city: Saint Petersburg
country: United States
facility: Coastal Pulmonary and Critical Care PLC
state: Florida
city: Weston
country: United States
facility: Weston Hospital
state: Florida
city: Atlanta
country: United States
facility: Piedmont Pulmonary and Sleep Medicine Buckhead
state: Georgia
city: Evergreen Park
country: United States
facility: GenHarp Clinical Solutions
state: Illinois
city: Glenview
country: United States
facility: Northwestern Medicine - Northwestern Medicine Glen
state: Illinois
city: Muncie
country: United States
facility: IU Health Ball Memorial Physicians Pulmonary and Critical Care Medicine
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
city: Hannibal
country: United States
facility: Hannibal Regional Healthcare System HRMG Hannibal
state: Missouri
city: Greensboro
country: United States
facility: Pulmonix LLC
state: North Carolina
city: Winston-Salem
country: United States
facility: Southeastern Research Center
state: North Carolina
city: Oklahoma City
country: United States
facility: The University of Oklahoma Health Sciences Center
state: Oklahoma
city: Dallas
country: United States
facility: Baylor Scott and White Health - Advanced Lung Disease Specialists - Dallas
state: Texas
city: Dallas
country: United States
facility: IntraCare Health Center ? Prestige
state: Texas
city: El Paso
country: United States
facility: El Paso Pulmonary Association Elligo PPDS
state: Texas
city: Houston
country: United States
facility: McGovern Medical School
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah - PPDS
state: Utah
city: Buenos Aires
country: Argentina
facility: Centro Médico Dra de Salvo
city: Ciudad Autonoma Buenos Aires
country: Argentina
facility: Consultorios Médicos Dr. Doreski
city: Mar Del Plata
country: Argentina
facility: Instituto Ave Pulmo
city: Mendoza, Mendoza City
country: Argentina
facility: INSARES
city: Mendoza
country: Argentina
facility: Fundacion Scherbovsky
city: Rio Cuarto
country: Argentina
facility: Instituto Medico Rio Cuarto
city: Rosario
country: Argentina
facility: Instituto Medico de la Fundacion Estudios Clinicos
city: San Miguel de Tucuman
country: Argentina
facility: Instituto De Patologias Respiratorias
city: San Miguel de Tucuman
country: Argentina
facility: Centro de Investigaciones Medicas Tucuman
city: San Miguel de Tucuman
country: Argentina
facility: Centro de Investigaciones Reumatologicas
city: Santa Fe
country: Argentina
facility: Instituto Del Buen Aire
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: Clayton
country: Australia
facility: Monash Health Monash Medical Centre
state: Victoria
city: Aalst
country: Belgium
facility: AZORG Campus Aalst-Moorselbaan
city: Liège
country: Belgium
facility: CHU de Liège
city: Roeselare
country: Belgium
facility: AZ Delta
city: Brasilia
country: Brazil
facility: L2 Ip - Instituto de Pesquisas Clinicas Ltda - ME
state: Distrito Federal
city: Brasilia
country: Brazil
facility: Hospital Brasilia
state: Distrito Federal
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre HCPA PPDS
state: Pará
city: Blumenau
country: Brazil
facility: Hospital Dia do Pulmao
state: Santa Catarina
city: Kelowna
country: Canada
facility: Kelowna Allergy and Respiratory Health Clinic
state: British Columbia
city: Ajax
country: Canada
facility: Dynamic Drug Advancement Ltd.
state: Ontario
city: Windsor
country: Canada
facility: Dr Anil Dhar Professional Medicine Corporation
state: Ontario
city: Nunoa
country: Chile
facility: CEC SpA
city: Providencia
country: Chile
facility: Enroll SpA - PPDS
city: Talca
country: Chile
facility: Centro de Investigacion del Maule
city: Bobigny
country: France
facility: Hopital Avicenne
city: Bron
country: France
facility: Hopital Louis Pradel
city: Marseille
country: France
facility: Hopital Nord AP-HM
city: Montpellier
country: France
facility: Hôpital Arnaud de Villeneuve
city: Nice Cedex 1
country: France
facility: Hopital Pasteur 2
city: Paris
country: France
facility: Groupe Hospitalier Bichat Claude Bernard
city: Reims
country: France
facility: CHU de Reims
city: Berlin
country: Germany
facility: Evangelische Lungenklinik Berlin
city: Essen
country: Germany
facility: Ruhrlandklinik
city: Herakleion
country: Greece
facility: University General Hospital of Heraklion
city: Larissa
country: Greece
facility: University General Hospital of Larissa
city: Székesfehérvár
country: Hungary
facility: Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Beer Jacob
country: Israel
facility: Shamir Medical Center Assaf Harofeh
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petah Tikva
country: Israel
facility: Rabin Medical Center
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv-Yafo
country: Israel
facility: Tel Aviv Sourasky Medical Center PPDS
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese
state: Abruzzo
city: Forli'
country: Italy
facility: Presidio Ospedaliero GB Morgagni L Pierantoni
state: Emilia-Romagna
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova
state: Emilia-Romagna
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli
state: Lazio
city: Milano
country: Italy
facility: Ospedale S. Giuseppe Multimedica
state: Lombardia
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona-Umberto I G.M. Lancisi G. Salesi
state: Marche
city: Torino
country: Italy
facility: Azienda Ospedaliera Città della Salute e della Scienza di Torino
state: Piemonte
city: Catania
country: Italy
facility: Azienda Ospedaliera Universitaria "Policlinico - Vittorio Emanuele" (Presidio Gaspare Rodolico)
state: Sicilia
city: Florence
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
state: Toscana
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Eunpyeong St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Hanyang University Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - PPDS
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center - PPDS
city: Americana
country: Mexico
facility: CICUM San Miguel
state: Jalisco
city: Guadalajara
country: Mexico
facility: Bioclinica - Centro Integral En Reumatologia Sociedad Anónima de Capital Variable - PPDS
state: Jalisco
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr. Jose Eleuterio Gonzalez
state: Nuevo LEON
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Lodz
country: Poland
facility: SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi
city: Rzeszow
country: Poland
facility: EMED Centrum Uslug Medycznych Ewa Smialek
city: Sosnowiec
country: Poland
facility: PULMAG Grzegorz Gasior Marzena Kociolek Spolka Cywilna
city: Warszawa
country: Poland
facility: Wojskowy Instytut Medyczny Panstwowy Instytut Badawczy
city: Cape Town
country: South Africa
facility: Dr JM Engelbrecht Trial site
city: Cape Town
country: South Africa
facility: University of Cape Town Lung Institute UCTLI
city: Durban
country: South Africa
facility: St Augustines Hospital
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
state: Cantabria
city: Santiago de Compostela
country: Spain
facility: CHUS H Clinico U de Santiago
state: LA Coruna
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Palma de Mallorca
country: Spain
facility: Hospital Universitario Son Espases
city: New Taipei
country: Taiwan
facility: Far East Memorial Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei City
country: Taiwan
facility: Taipei Veterans General Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: