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

Idiopathic Pulmonary Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05785624
• Other study ID #: GB44496
• Secondary ID: 2022-502828-42
• Status: Recruiting
• Phase: Phase 2
• Start date: May 26, 2023
• Est. completion date: August 10, 2027

Study information

• Verified date: April 2024
• Source: Genentech, Inc.
• Contact: Reference Study ID Number: GB44496 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. Only)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 320
• Est. completion date: August 10, 2027
• Est. primary completion date: April 26, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Lung Diseases
• Lung Diseases, Interstitial
• Pulmonary Fibrosis
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis With Lung Involvement

Intervention

Drug:
• Vixarelimab
Vixarelimab will be administered as per the schedule specified in the respective arms.
• Placebo
Placebo will be administered as per the schedule specified in the respective arms.

Locations

Country	Name	City	State
Argentina	Centro Médico Dra de Salvo	Buenos Aires
Argentina	Instituto Medico Rio Cuarto	Cordoba
Argentina	Instituto Ave Pulmo	Mar Del Plata
Argentina	Fundacion Scherbovsky	Mendoza
Argentina	INSARES	Mendoza, Mendoza City
Argentina	Instituto Medico de la Fundacion Estudios Clinicos	Rosario
Argentina	Centro de Investigaciones Reumatologicas	San Miguel de Tucuman
Argentina	Instituto De Patologias Respiratorias	San Miguel de Tucuman
Argentina	Instituto Del Buen Aire	Santa Fe
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Monash Health Monash Medical Centre	Clayton	Victoria
Australia	St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Belgium	Onze Lieve Vrouwziekenhuis Aalst	Aalst
Belgium	CHU de Liège	Liège
Belgium	AZ Delta	Roeselare
Brazil	Hospital Dia do Pulmao	Blumenau	SC
Brazil	L2 Ip - Instituto de Pesquisas Clinicas Ltda - ME	Brasilia	DF
Brazil	Hospital de Clinicas de Porto Alegre HCPA PPDS	Porto Alegre	PA
Canada	Dynamic Drug Advancement Ltd.	Ajax	Ontario
Canada	Kelowna Allergy and Respiratory Health Clinic	Kelowna	British Columbia
Canada	Dr Anil Dhar Professional Medicine Corporation	Windsor	Ontario
Chile	CEC SpA	Nunoa
Chile	Enroll SpA - PPDS	Providencia
Chile	Centro de Investigacion del Maule	Talca
France	Hopital Avicenne	Bobigny
France	Hopital Louis Pradel	Bron
France	Hopital Nord AP-HM	Marseille
France	Hôpital Arnaud de Villeneuve	Montpellier
France	Hopital Pasteur 2	Nice Cedex 1
France	Groupe Hospitalier Bichat Claude Bernard	Paris
France	CHU de Reims	Reims
Greece	University General Hospital of Heraklion	Heraklio
Greece	University General Hospital of Larissa	Larissa
Israel	Barzilai Medical Center	Ashkelon
Israel	Shamir Medical Center Assaf Harofeh	Beer Jacob
Israel	Lady Davis Carmel Medical Center	Haifa
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Rabin Medical Center	Petah Tikva
Israel	Sheba Medical Center - PPDS	Ramat Gan
Israel	Kaplan Medical Center	Rehovot
Israel	Tel Aviv Sourasky Medical Center PPDS	Tel Aviv-Yafo
Italy	Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele	Catania	Sicilia
Italy	Azienda Ospedaliera Universitaria Careggi	Florence	Toscana
Italy	Presidio Ospedaliero GB Morgagni L Pierantoni	Forli'	Emilia-Romagna
Italy	Ospedale S. Giuseppe Multimedica	Milano	Lombardia
Italy	Fondazione Policlinico Universitario A Gemelli	Roma	Lazio
Italy	Azienda Ospedaliera Universitaria Senese	Siena	Abruzzo
Italy	Azienda Ospedaliera Città della Salute e della Scienza di Torino	Torino	Piemonte
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Asan Medical Center - PPDS	Seoul
Korea, Republic of	Hanyang University Medical Center	Seoul
Korea, Republic of	Samsung Medical Center - PPDS	Seoul
Korea, Republic of	The Catholic University of Korea Eunpyeong St. Mary's Hospital	Seoul
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Dunedin Hospital	Dunedin
New Zealand	Waikato Hospital	Hamilton
Poland	SPZOZ Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego Uniwersytetu Medycznego w Lodzi	Lodz
Poland	EMED Centrum Uslug Medycznych Ewa Smialek	Rzeszów
Poland	PULMAG Grzegorz Gasior Marzena Kociolek Spolka Cywilna	Sosnowiec
South Africa	Dr JM Engelbrecht Trial site	Cape Town
South Africa	Panorama Medical Centre	City Of Cape Town
South Africa	St Augustines Hospital	Durban
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Malaga
Spain	Hospital Universitario Son Espases	Palma de Mallorca	Islas Baleares
Spain	Hospital Universitario Marques de Valdecilla	Santander	Cantabria
Spain	CHUS H Clinico U de Santiago	Santiago de Compostela	LA Coruña
Taiwan	Far East Memorial Hospital	New Taipei
Taiwan	Taipei Veterans General Hospital	Taipei City
United States	Piedmont Pulmonary and Sleep Medicine Buckhead	Atlanta	Georgia
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	El Paso Pulmonary Association Elligo PPDS	El Paso	Texas
United States	University of California, San Francisco-Fresno	Fresno	California
United States	Northwestern Medicine - Northwestern Medicine Glen	Glenview	Illinois
United States	Pulmonix LLC	Greensboro	North Carolina
United States	Hannibal Regional Healthcare System HRMG Hannibal	Hannibal	Missouri
United States	McGovern Medical School	Houston	Texas
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Research Centers of America	McKinney	Texas
United States	IU Health Ball Memorial Physicians Pulmonary and Critical Care Medicine	Muncie	Indiana
United States	Renstar Medical Research	Ocala	Florida
United States	The University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Central Florida Pulmonary Group, PA	Orlando	Florida
United States	Coastal Pulmonary and Critical Care PLC	Saint Petersburg	Florida
United States	University of California, San Francisco Medical Center	San Francisco	California
United States	Southeastern Research Center	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  Chile,  France,  Greece,  Israel,  Italy,  Korea, Republic of,  New Zealand,  Poland,  South Africa,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Cohorts 1 and 2: Absolute Change From Baseline in Forced Vital Capacity (FVC)	FVC is a pulmonary function test parameter that indicates the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It's measured by spirometry, which is a common breathing test to check lung function.	Baseline up to Week 52
Secondary	Cohorts 1 and 2: Absolute Change From Baseline in 6-Minute Walk Test (6MWT) Distance	The 6MWT test is performed indoors on a flat, straight corridor with a hard surface at least 30 meters (m) in length. 6MWT measures the distance a participant is able to walk quickly on a flat, hard surface in a period of 6 minutes. 6MWT measure will be calculated as the simple difference between baseline distance walked over 6 minutes and week 52 distance walked over 6 minutes as measured in meters.	Baseline up to Week 52
Secondary	Cohorts 1 and 2: Absolute Change From Baseline in Percentage of Predicted FVC	FVC is a pulmonary function test parameter that indicates the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It's measured by spirometry, which is a common breathing test to check lung function.	Baseline up to Week 52
Secondary	Cohorts 1 and 2: Change From Baseline in Diffusion Capacity of the Lung for Carbon Monoxide Adjusted for Hemoglobin (DLco [Hb])	DLCO measures the ability of the lungs to transfer gas from inhaled air to the red blood cells in the blood. DLCO is adjusted for hemoglobin as small changes in hemoglobin concentration can affect the carbon monoxide transfer.	Baseline up to Week 52
Secondary	Cohorts 1 and 2: Time to Disease Progression	Time to disease progression is defined as time to first occurrence of =10% absolute decline in percentage of predicted FVC, =15% relative decline in 6MWT distance, lung transplantation, or death. FVC=pulmonary function test parameter that indicates the amount of air that can be forcibly exhaled from the lungs after taking the deepest breath possible. It's measured by spirometry, which is a common breathing test to check lung function. 6MWT test is performed indoors on a flat, straight corridor with a hard surface at least 30 m in length. 6MWT measures the distance a participant is able to walk quickly on a flat, hard surface in a period of 6 minutes. 6MWT measure will be calculated as the simple difference between baseline distance walked over 6 minutes and week 52 distance walked over 6 minutes as measured in meters.	From the start of study treatment until disease progression or death, whichever occurs first (up to Week 52 of DBT)
Secondary	Cohorts 1 and 2: Time to First Acute Exacerbation of ILD, or Suspected Acute Exacerbation of ILD		From the start of study treatment until end of DBT (up to Week 52)
Secondary	Cohorts 1 and 2: Change From Baseline in Quantitative Lung Fibrosis on High-Resolution Computed Tomography (HRCT) Scan of the Thorax	High-resolution computer tomography (HRCT) is a type of computed tomography (CT) with specific techniques to enhance image resolution. It is used in the diagnosis of various health problems, most commonly for lung disease. These images show cross sections (slices) through the lungs.	Baseline up to Week 52
Secondary	Cohorts 1 and 2: Percentage of Participants with Deaths		Up to Week 52
Secondary	Cohort 2: Change From Baseline in Skin Sclerosis Assessed Using Modified Rodnan Skin Score (mRSS)	mRSS is a measure of skin thickness. Skin thickness will be assessed by the investigator by palpation across 17 different body sites and scored on a scale of 0 (normal) to 3 (severe skin thickening). The total score is the sum of the individual skin scores from all of these sites and ranges from 0 (normal) to 51 (severe thickening in all 17 areas) units. Higher scores indicate disease worsening.	Baseline up to Week 52
Secondary	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	K-BILD is a questionnaire that assesses HRQoL in ILDs. It consists of 15 items grouped into psychological, breathlessness and activity, and chest symptom domains, each scored individually on a 7-point scale, with domain-level and total scores transformed 0-100, with higher scores indicating better quality of life. It uses a 2-week recall period.	Baseline up to Week 52
Secondary	Cohorts 1 and 2: Change From Baseline in Cough Measured Using Living with Pulmonary Fibrosis (L-PF) Symptoms Cough Domain Score	The L-PF symptoms module is a 23-item tool with domains capturing shortness of breath, cough, and energy symptoms using a 0-4 numeric response scale (NRS) response format and a 24-hour recall period. The cough scores ranges from 0 to 100 with higher scores indicating greater symptom burden/impairment.	Baseline up to Week 52
Secondary	Cohorts 1 and 2: Change From Baseline in Dyspnea Measured Using L-PF Symptoms Dyspnea Domain Score	The L-PF symptoms module is a 23-item tool with domains capturing shortness of breath, cough, and energy symptoms using a 0-4 NRS response format and a 24-hour recall period. L-PF Symptoms Dyspnea Domain score (dyspnea score) ranges from 0 to 100, with higher score indicating greater impairment.	Baseline up to Week 52
Secondary	Cohort 2: Change From Baseline in Pruritus Measured Using the Five-Dimension Itch Scale (5-D Itch) Total Score	The 5-D-Itch questionnaire that measures itch and its impact. It consists of 8 items organized into 5 domains (duration, degree, direction, disability, and distribution). Each domain is scored 1 to 5 with a total score ranging from 5 to 25 with higher scores indicating greater itch severity.	Baseline up to Week 52
Secondary	Cohorts 1, 2 and OLE Period: Number of Participants With Adverse Events (AEs)		Up to Week 52
Secondary	Cohorts 1 and 2: Serum Concentration of Vixarelimab		Baseline up to Week 52
Secondary	Cohorts 1 and 2: Number of Participants With Anti-Drug Antibodies (ADAs) to Vixarelimab		Baseline up to Week 52