Clinical trial NCT01769196: Study to Assess the Efficacy and Safety of Simtuzumab (GS-6624) in Adults With Idiopathic Pulmonary Fibrosis (IPF)
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Assess the Efficacy and Safety of Simtuzumab (GS-6624) in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: Idiopathic
Pulmonary
Fibrosis
IPF
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2013-01-16
Enrollment: 544
Sex: ALL
Minimum age (years): 45
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objectives of this study are to determine the effect of simtuzumab (GS-6624) on progression-free survival (PFS) as determined by either a categorical decline in forced vital capacity (FVC) or all-cause mortality, in all participants enrolled or in a subset of participants who are classified as lysyl oxidase-like-2 (LOXL2) high based on a prespecified level in serum at baseline.


Eligibility criteria: Key Inclusion Criteria:

* Male or female subjects from 45 to 85 years of age
* Definite IPF within 3 years prior to screening
* Be able to walk at least 50 meters

Key Exclusion Criteria:

* Significant diseases other than IPF
* Obstructive lung disease
* Aortic aneurysm greater than or equal to 3.5 cm in diameter
* Treatment with immunosuppressive, cytotoxic, or antifibrotic drugs \< 28 days prior to randomization are not permitted.

  * N-acetylcysteine is permitted provided the individual has been on a stable dose for \> 4 weeks prior to screening
  * Concomitant use of pirfenidone or nintedanib must be in accordance with the approved prescribing instructions in the country where the site is located
* Individuals actively listed for lung transplant are excluded. However individuals at transplant centers with long waiting times (greater than 1 year) may be permitted to enter the study after discussion with Medical Monitor.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Progression Free Survival
timeFrame: Up to 148 weeks
measure: PFS Among the Participants With sLOXL2 ≥ 50th Percentile
timeFrame: Up to 148 weeks
measure: PFS Among the Participants With sLOXL2 ≥ 75th Percentile
timeFrame: Up to 148 weeks
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to 151 weeks
measure: Overall Survival Among the Participants With sLOXL2 ≥ 50th Percentile
timeFrame: Up to 151 weeks
measure: Overall Survival Among the Participants With sLOXL2 ≥ 75th Percentile
timeFrame: Up to 151 weeks
measure: Relative Change From Baseline in FVC % Predicted
timeFrame: Weeks 54, 106, and 130
measure: Definite Acute Exacerbations of IPF Among Adjudicated Respiratory Hospitalizations
timeFrame: Up to 148 weeks
measure: Number of Adjudicated Respiratory Hospitalizations (ARP) Among Total Hospitalizations
timeFrame: Up to 148 weeks
measure: Number of Participants Experiencing Adjudicated Respiratory Deaths Among Those With Adjudicated Death
timeFrame: Up to 148 weeks
measure: Absolute Change From Baseline in 6 Minute Walk Distance (6MWD)
timeFrame: Weeks 58, 106, and 130
measure: Absolute Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Score
timeFrame: Week 58, 106, and 130
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Arizona Pulmonary Specialists, Ltd.
state: Arizona
city: Phoenix
country: United States
facility: Saint Joseph's Hospital and Medical Center
state: Arizona
city: Scottsdale
country: United States
facility: Arizona Pulmonary Specialists, Ltd.
state: Arizona
city: Scottsdale
country: United States
facility: Mayo Clinic Arizona
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona
state: Arizona
city: La Jolla
country: United States
facility: University of California San Diego
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at University of California, Los Angeles
state: California
city: Sacramento
country: United States
facility: University of California Davis Medical Center
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Clearwater
country: United States
facility: Bay Area Chest Physicians
state: Florida
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Mayo Clinic Florida
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Sarasota
country: United States
facility: Sarasota Memorial Hospital
state: Florida
city: Tampa
country: United States
facility: Tampa General Hospital
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Decatur
country: United States
facility: Southeastern Lung Care
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Council Bluffs
country: United States
facility: Loess Hills Clinical Research Center
state: Iowa
city: Iowa City
country: United States
facility: University of Iowa Hospitals and Clinics
state: Iowa
city: Louisville
country: United States
facility: Kentuckiana Pulmonary Associates
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: New Orleans
country: United States
facility: Tulane University School of Medicine
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Tufts University School of Medicine
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Chesterfield
country: United States
facility: CardioPulmonary Associates
state: Missouri
city: Kansas City
country: United States
facility: Saint Luke's Midwest Pulmonary Consultants
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: New Brunswick
country: United States
facility: Robert Wood Johnson Medical School
state: New Jersey
city: Summit
country: United States
facility: Pulmonary and Allergy Associates, PA
state: New Jersey
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Jamaica
country: United States
facility: Jamaica Hospital Medical Center
state: New York
city: New Hyde Park
country: United States
facility: North Shore University Hospital
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Rochester
country: United States
facility: University of Rochester
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Dayton
country: United States
facility: Miami Valley Hospital
state: Ohio
city: Portland
country: United States
facility: The Oregon Clinic, PC
state: Oregon
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital, Temple Lung Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Presbyterian - Montefiore
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Falls Church
country: United States
facility: Inova Fairfax Hospital
state: Virginia
city: Everett
country: United States
facility: Providence Everett Medical Center
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Hospital and Medical College of Wisconsin
state: Wisconsin
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
state: New South Wales
city: Darlinghurst
country: Australia
facility: Saint Vincents Hospital
state: New South Wales
city: Brisbane
country: Australia
facility: Mater Adult Hospital
state: Queensland
city: Chermside
country: Australia
facility: Prince Charles Hospital
state: Queensland
city: Herston
country: Australia
facility: Royal Brisbane and Women's Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Perth
country: Australia
facility: Royal Perth Hospital
state: Western Australia
city: Anderlecht
country: Belgium
facility: ULB Erasme
state: Brussels
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
state: Flemish Brabant
city: Yvoir
country: Belgium
facility: Cliniques Universitaires UCL de Mont-Godinne
state: Namur
city: Kelowna
country: Canada
facility: Kelowna Respiratory and Allergy Clinic
state: British Columbia
city: Vancouver
country: Canada
facility: Vancouver General Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: University of British Columbia
state: British Columbia
city: Hamilton
country: Canada
facility: Saint Joseph's Healthcare
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Montreal
country: Canada
facility: Centre Hospitalier de L'Université de Montréal Hôtel-Dieu
state: Quebec
city: Quebec City
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec
state: Quebec
city: Brno
country: Czechia
facility: Fakultní nemocnice Brno
state: Jihormoravsky Kraj
city: Jihlava
country: Czechia
facility: Nemocnice Jihlava
state: Jihormoravsky Kraj
city: Liberec
country: Czechia
facility: Krajská nemocnice Liberec a.s.
state: Severocesky Kraj
city: Ústí nad Labem
country: Czechia
facility: Masarykova nemocnice v Ústí nad Labem o.z.
state: Severocesky Kraj
city: Ostrava - Poruba
country: Czechia
facility: Fakultní Nemocnice Ostrava
state: Severomoravsky Kraj
city: Plzen
country: Czechia
facility: Fakultní nemocnice Plzen
state: Zapadocesky Kraj
city: Prague 4 - Krc
country: Czechia
facility: Thomayerova nemocnice
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
state: Alsace
city: Rennes cedex 9
country: France
facility: Centre Hospitalier Universitaire de Rennes, Hôpital Pontchaillou
state: Bretagne
city: Tours Cedex 9
country: France
facility: Centre Hospitalier Régional et Universitaire - Hôpital Bretonneau
state: Centre
city: Bobigny Cedex
country: France
facility: Centre Hospitalier Universitaire Hôpital Avicenne
state: Ile-de-france
city: Paris Cedex 15
country: France
facility: HEGP
state: Ile-de-france
city: Paris
country: France
facility: Hôpital Bichat-Claude Bernard
state: Ile-de-france
city: Montpellier cedex 5
country: France
facility: Hôpital Arnaud de Villeneuve
state: Languedoc-roussillon
city: Toulouse cedex 9
country: France
facility: Hôpital Larrey, CHU de Toulouse, Service de Pneumologie
state: Midi-pyrenees
city: Lille cedex
country: France
facility: Hôpital Albert Calmette
state: Nord Pas-de-calais
city: Nice CEDEX 1
country: France
facility: Centre Hospitalier Universitaire de Nice-Hôpital Pasteur
state: Poitou-charentes
city: Marseille Cedex 20
country: France
facility: Centre Hospitalier Universitaire Hôpital Nord
state: Provence Alpes Cote D'azur
city: Grenoble Cedex 9
country: France
facility: Centre Hospitalier Universitaire Grenoble Hopital Michalon
state: Rhone-Alpes
city: Bron
country: France
facility: Hôpital Louis Pradel
state: Rhone-aples
city: Freiburg
country: Germany
facility: Universität Freiburg, Klinikum, Abt für Pneumologie
state: Baden-wuerttemberg
city: Heidelberg
country: Germany
facility: Thoraxklinik am Universitätsklinikum Heidelberg
state: Baden-wuerttemberg
city: Mannheim
country: Germany
facility: Ruhrlandklinik
state: Baden-wuerttemberg
city: München
country: Germany
facility: Klinikum Großhadern der Ludwig-Maximilians-Universität München
state: Bayern
city: Giessen
country: Germany
facility: Philipps-Universität und Universitätsklinikum Gießen und Marburg GmbH
state: Hessen
city: Immenhausen
country: Germany
facility: Lungenfachklinik Immenhausen
state: Hessen
city: Hanover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Coswig
country: Germany
facility: Fachkrankenhaus Coswig
state: Sachsen
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
state: Sachsen
city: Berlin
country: Germany
facility: Helios Klinikum Emil von Behring, Lungenklinik Heckeshorn
city: Beer Sheva
country: Israel
facility: Soroka University Medical Center
state: Beersheba
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center
state: Tel Aviv
city: Jerusalem
country: Israel
facility: Hadassah-Hebrew University Medical Center
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Petach Tikvah
country: Israel
facility: Rabin Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Center
city: Forlì
country: Italy
facility: Ospedale "G.B.Morgagni - L. Pierantoni"
state: Forli-cesena
city: Monza
country: Italy
facility: Azienda Ospedaliera San Gerardo di Monza
state: Monza E Brianza
city: Catania
country: Italy
facility: Policlinico Universitario di Catania
city: Milano
country: Italy
facility: San Giuseppe Hospital, Dept. of Internal Medicine
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria Policlinico di Modena
city: Napoli
country: Italy
facility: Università degli studi Federico II di Napoli
city: Palermo
country: Italy
facility: Istituto Mediterraneo Trapianti e Terapia Alta Specializzazione (ISMETT)
city: Roma
country: Italy
facility: Fondazione PTV - Policlinico Tor Vergata
city: Siena
country: Italy
facility: Azienda Ospedaliera Universitaria Senese Policlinico Le Scotte
city: Bucheon-si
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital Bucheon
state: Gyeonggi-do
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
state: Gyeonggi-Do
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Bydgoszcz
country: Poland
facility: 10 Wojskowy Szpital Kliniczny z Poliklinika SP ZOZ w Bydgoszczy
state: Kujawsko-pomorskie
city: Lódz
country: Poland
facility: Samodzielny Publiczny ZOZ, Uniwersytecki Szpital Kliniczny nr 1 im. Norberta Barlickiego
state: Lodzkie
city: Warszawa
country: Poland
facility: Instytut Gruzlicy i Chorób Pluc
state: Mazowieckie
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
state: Pomorskie
city: Zabrze
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 3 w Zabrzu Slaskiego Uniwersytetu Medycznego w Katowicach
state: Slaskie
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Asturias
city: Pozuelo de Alarcón
country: Spain
facility: Hospital Quirón Madrid
state: Madrid
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Universitario La Princesa
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
state: Sankt Gallen
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois Lausanne (CHUV)
state: Vaud
city: Basel
country: Switzerland
facility: Universitätsspital Basel
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
state: England
city: Bristol
country: United Kingdom
facility: Southmead Hospital
state: England
city: Cambridge
country: United Kingdom
facility: Papworth Hospital
state: England
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital
state: England
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
state: England
city: Leeds
country: United Kingdom
facility: Saint James's University Hospital
state: England
city: Leicester
country: United Kingdom
facility: Glenfield Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Aintree University Hospitals NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: Royal Brompton Hospital
state: England
city: Manchester
country: United Kingdom
facility: University Hospital of South Manchester NHS Foundation Trust
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
state: England
city: Oxford
country: United Kingdom
facility: Churchill Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Northern General Hospital
state: England
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: England
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
state: Scotland
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
state: Scotland
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Raghu G, Brown KK, Collard HR, Cottin V, Gibson KF, Kaner RJ, Lederer DJ, Martinez FJ, Noble PW, Song JW, Wells AU, Whelan TP, Wuyts W, Moreau E, Patterson SD, Smith V, Bayly S, Chien JW, Gong Q, Zhang JJ, O'Riordan TG. Efficacy of simtuzumab versus placebo in patients with idiopathic pulmonary fibrosis: a randomised, double-blind, controlled, phase 2 trial. Lancet Respir Med. 2017 Jan;5(1):22-32. doi: 10.1016/S2213-2600(16)30421-0. Epub 2016 Dec 7.
citation: Humphries SM, O'Riordan TG, Zhang JJ, Bayly S, Sood R, Hayden A, Lynch DA; Relationship Baseline Fibrosis Score to Lung Function in A Clinical Trial Population with Idiopathic Pulmonary Fibrosis. ATS International Conference, 2016 May 13-18, San Francisco CA.
citation: Raghu G, Brown K, Collard H, Lederer D, Martinez F, Noble P, Song JW, Wells A, Whelan T, Moreau E, Patterson S, Bayly S, Chien J, Zhang J, O'Riordan T; Simtuzumab in Idiopathic Pulmonary Fibrosis: Results of a Randomized Clinical Trial. ERS Congress, 2016 September 3-7, London, UK.
citation: Raghu G, Brown KK, Collard HR, Lederer DJ, Martinez FJ, Noble PW, Song JW, Wells AU, Whalen TP, Lambert L, Chien JW, Zhang JJ, O'Riordan TG; Simtuzumab in Idiopathic Pulmonary Fibrosis (IPF): Baseline Demographic and Lung Function Data from a Clinical Trial. ATS International Conference, 2016 May 13-18, San Francisco CA.