Clinical trial NCT01890265: Evaluate the Safety and Efficacy of FG-3019 (Pamrevlumab) in Participants With Idiopathic Pulmonary Fibrosis (IPF)
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of FG-3019 in Patients With Idiopathic Pulmonary Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: Idiopathic Pulmonary Fibrosis
IPF
Idiopathic Interstitial Pneumonia
Interstitial Lung Disease
Lung Fibrosis
Lead sponsor: FibroGen
Sponsor class: INDUSTRY
First posted: 2013-07-01
Enrollment: 160
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the safety and tolerability of pamrevlumab in participants with IPF, and the efficacy of pamrevlumab in slowing the loss of forced vital capacity (FVC) and the progression of IPF in these participants.

Detailed description: The study has been amended in February 2016 to further allow for the enrollment of a subgroup of participants (N=60) who will be allowed to receive treatment with approved IPF therapy with pirfenidone or with nintedanib as concomitant therapy.

These additional participants will be stratified by background therapy, randomized to pamrevlumab or placebo, and followed up for 24 weeks. The main objective of the study remains safety. Pharmacokinetic (PK) samples to assess drug concentrations will also be collected.

This sub-study portion only applies to a select United States centers.

Enrollment for the main study was completed on 29 June 2016. Enrollment for the sub-study was completed on 16 December 2016.

Eligibility criteria: Inclusion Criteria:

1. Age 40 to 80 years, inclusive.
2. Diagnosis of IPF as defined by current international guidelines. Each participant must have 1 of the following: (1) Usual Interstitial Pneumonia (UIP) Pattern on an available high-resolution computed tomography (HRCT) scan; or (2) Possible UIP Pattern on an available HRCT scan and surgical lung biopsy within 4 years of Screening showing UIP Pattern.
3. History of IPF of ≤5 years duration with onset defined as the date of the first diagnosis of IPF by HRCT or surgical lung biopsy.
4. Interstitial pulmonary fibrosis defined by HRCT scan at Screening, with evidence of ≥10% to \<50% parenchymal fibrosis (reticulation) and \<25% honeycombing, within the whole lung, as determined by the HRCT central reader.
5. FVC percent of predicted value ≥55% at Screening.
6. Female participants of childbearing potential (including those \<1 year postmenopausal) must be willing to use a medically acceptable method of contraception, for example, an oral contraceptive, depot progesterone, or intrauterine device. Male participants with female partners of childbearing potential who are not using birth control as described above must use a barrier method of contraception (for example, condom) if not surgically sterile (for example, vasectomy).
7. For sub-study only: Receiving treatment for IPF with a stable dose of pirfenidone or with a stable dose of nintedanib for at least 3 months before Screening initiation and willing to continue treatment with pirfenidone or with nintedanib according to the corresponding approved label and the prescribing physician, including all listed safety requirements (for example, liver function tests, avoidance of sunlight and sunlamp exposure and wearing of sunscreen and protective clothing daily for pirfenidone, and smoking cessation).

Exclusion Criteria:

1. Women who are pregnant or nursing.
2. Infiltrative lung disease other than IPF, including any of the other types of idiopathic interstitial pneumonias (Travis, 2013); lung diseases related to exposure to fibrogenic agents or other environmental toxins or drugs; other types of occupational lung diseases; granulomatous lung diseases; pulmonary vascular diseases; systemic diseases, including vasculitis and connective tissue diseases.
3. HRCT scan findings at Screening are inconsistent with UIP Pattern, as determined by the HRCT central reader.
4. Pathology diagnosis on surgical lung biopsy is anything other than UIP Pattern, as determined by the local pathologist.
5. The Investigator judges that there has been sustained improvement in the severity of IPF during the 12 months prior to Screening, based on changes in FVC, diffusing capacity of the lung for carbon monoxide (DLCO), and/or HRCT scans of the chest.
6. Clinically important abnormal laboratory tests.
7. Upper or lower respiratory tract infection of any type within 4 weeks of the first Screening visit.
8. Acute exacerbation of IPF within 3 months of the first Screening visit.
9. Use of medications to treat IPF within 5 half-lives of Day 1 dosing. If monoclonal antibodies were used, the last dose of the antibody must be at least 4 weeks before Day 1 dosing. This applies to participants enrolled in Main Study only.
10. Use of any investigational drugs, including any investigational drugs for IPF, within 4 weeks prior to Day 1 dosing.
11. History of cancer diagnosis of any type in the 3 years preceding Screening, excluding non-melanomatous skin cancer, localized bladder cancer, or in situ cancers.
12. Diffusing capacity (DLCO) less than 30% of predicted value.
13. History of allergic or anaphylactic reaction to human, humanized, chimeric, or murine monoclonal antibodies.
14. Previous treatment with FG-3019.
15. Body weight greater than 130 kilograms.

Primary outcomes:
measure: Change From Baseline in FVC (Percent of Predicted FVC Value [% Predicted]) to Week 48
timeFrame: Baseline (Screening and Day 1), Week 48
Secondary outcomes:
measure: Mean Change From Baseline in the HRCT Quantitative Lung Fibrosis (QLF) Score to Week 24 and Week 48
timeFrame: Baseline (Screening), Week 24 and Week 48
measure: Number of Participants With IPF Progression Events up to Week 48
timeFrame: Baseline (Screening and Day 1) up to Week 48
measure: Mean Change From Baseline in the Health-Related Quality of Life (HRQoL) Saint George's Respiratory Questionnaire (SGRQ) Domain and Total Scores to Week 24 and Week 48
timeFrame: Baseline (Day 1), Week 24 and Week 48
measure: Number of Participants With a Respiratory-Related Hospitalization
timeFrame: Week 55
measure: Number of Participants With a Respiratory-Related Death
timeFrame: Week 55
measure: Number of Participants With No Decline in FVC (% Predicted) at Week 48
timeFrame: Baseline (Day 1) to Week 48.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The Kirklin Clinic
state: Alabama
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Sacramento
country: United States
facility: UC Davis Medical Center
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Kissimmee
country: United States
facility: Pulmonary Disease Specialist, PA
state: Florida
city: Pensacola
country: United States
facility: Pensacola Research Consultants, Inc., d.b.a. Avanza Medical Research Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Wichita
country: United States
facility: Via Christi Clinic, P.A.
state: Kansas
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Boston
country: United States
facility: Steward St. Elizabeth's Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Medical Center
state: Michigan
city: Chesterfield
country: United States
facility: St. Luke's Hospital
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Greensboro
country: United States
facility: PulmonIx LLC
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cinncinati
state: Ohio
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: Ohio
city: Portland
country: United States
facility: Legacy Research Institute
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah - Lung Health Research
state: Utah
city: Colchester
country: United States
facility: Vermont Lung Center
state: Vermont
city: Concord
country: Australia
facility: Concord Repatriation
state: New South Wales
city: Adelaide
country: Australia
facility: Daw Park Repatriation
state: South Australia
city: Sofia
country: Bulgaria
facility: MHAT 'Tokuda Hospital Sofia', AD, Department of Pulmonology
city: Greenfield Park
country: Canada
facility: Université de Sherbrooke / Hôpital Charles LeMoyne
state: Quebec
city: Bangalore
country: India
facility: St Johns Medical College Hospital
state: Karnataka
city: Mumbai
country: India
facility: Bhatia Hospital
state: Maharashtra
city: Coimbatore
country: India
facility: Sri Bala Medical Centre and Hospital
state: Tamil Nadu
city: Lucknow
country: India
facility: Midland Healthcare & Research Center
state: Uttar Pradesh
city: Kolkata
country: India
facility: Fortis Hospitals
state: West Bengal
city: Christchurch
country: New Zealand
facility: Christchurch Hospital NZ
city: Dunedin
country: New Zealand
facility: Dunedin Public Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Tauranga
country: New Zealand
facility: Tauranga Hospital
city: Pretoria
country: South Africa
facility: Into Research
state: Gauteng
city: Durban
country: South Africa
facility: Life Mount Edgecombe Hospital
state: KwaZulu-Natal
city: Cape Town
country: South Africa
facility: Tygerberg Hospital Respiratory Research Unit
state: Western Cape
Study officials:
affiliation: Via Christi Clinic, P.A., USA
name: Mark Wencel, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: The Kirklin Clinic, USA
name: Joao de Andrade, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Steward St. Elizabeth's Medical Center, USA
name: Peter LaCamera, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University, USA
name: Danielle Antin-Ozerkis, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University
name: Rishi Raj, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: St Luke's Hospital, USA
name: Neil Ettinger, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Louisville, USA
name: Rafael Perez, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California Davis Medical Center, USA
name: Timothy Albertson, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Vermont Lung Center, USA
name: Yolanda Mageto, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Emory University, USA
name: Srihari Veeraraghavan, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Cinncinati, USA
name: Nishant Gupta, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pittsburgh Medical Center, USA
name: Kevin Gibson, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Vanderbilt University, USA
name: Lisa Lancaster, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Utah - Lung Health Research, USA
name: Mary Beth Scholand, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Kansas Medical Center, USA
name: Mark Hamblin, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Texas Southwestern Medical Center, USA
name: John Fitzgerald, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: David Geffen School of Medicine at UCLA, USA
name: John Belperio, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Dartmouth-Hitchcock Medical Center, USA
name: Richard Enelow, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: National Jewish Center, USA
name: Evans R Fernandez-Perez, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Pensacola Research Consultants, INC., USA
name: Peter A Bercz, M.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Henry Ford Medical Center, USA
name: Krishna Thavarajah, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Maryland, College Park
name: James Britt, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Legacy Research Institute, USA
name: Danielle D. Hosmer
role: PRINCIPAL_INVESTIGATOR
affiliation: Columbia University Medical Center, USA
name: David Lederer, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: PulmonIx LLC, USA
name: Murali Ramaswamy, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Pulmonary Disease Specialist, PA, USA
name: Thomas O'Brien, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Université de Sherbrooke / Hôpital Charles LeMoyne, Canada
name: Nadim Srour, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Tygerberg Hospital Respiratory Research Unit, South Africa
name: Elvis Irusen, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Life Mount Edgecombe Hospital, South Africa
name: Anish Ambaram, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Into Research, South Africa
name: Heidi Siebert, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Concord Repatriation, Australia
name: Elizabeth Veitch, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Daw Park Repatriation, Australia
name: Huw Davies, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Christchurch Hospital NZ, New Zealand
name: Lutz Beckert, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Waikato Hospital, New Zealand
name: Catherina Chang, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Dunedin Public Hospital, New Zealand
name: Benedict Brockway, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Tauranga Hospital, New Zealand
name: Suzanne Poole, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Fortis Hospitals, India
name: Raja Dhar, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Midland Healthcare & Research Center, India
name: Bhanu Singh, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Sri Bala Medical Centre and Hospital, India
name: Nandagopal Velayuthaswamy, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Bhatia Hospital, India
name: Sujeet Rajan, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: St Johns Medical College Hospital, India
name: Priya Ramachandran, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: MHAT 'Tokuda Hospital Sofia', AD, Department of Pulmonology, Bulgaria
name: Natalia Stoeva, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lipson KE, Wong C, Teng Y, Spong S. CTGF is a central mediator of tissue remodeling and fibrosis and its inhibition can reverse the process of fibrosis. Fibrogenesis Tissue Repair. 2012 Jun 6;5(Suppl 1):S24. doi: 10.1186/1755-1536-5-S1-S24. eCollection 2012.
citation: Richeldi L, Fernandez Perez ER, Costabel U, Albera C, Lederer DJ, Flaherty KR, Ettinger N, Perez R, Scholand MB, Goldin J, Peony Yu KH, Neff T, Porter S, Zhong M, Gorina E, Kouchakji E, Raghu G. Pamrevlumab, an anti-connective tissue growth factor therapy, for idiopathic pulmonary fibrosis (PRAISE): a phase 2, randomised, double-blind, placebo-controlled trial. Lancet Respir Med. 2020 Jan;8(1):25-33. doi: 10.1016/S2213-2600(19)30262-0. Epub 2019 Sep 28.