Evaluate the Safety and Efficacy of FG-3019 (Pamrevlumab) in Participants With Idiopathic Pulmonary Fibrosis (IPF)

Idiopathic Pulmonary Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01890265
• Other study ID #: FGCL-3019-067
• Status: Completed
• Phase: Phase 2
• Start date: July 30, 2013
• Est. completion date: November 16, 2017

Study information

• Verified date: August 2020
• Source: FibroGen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 160
• Est. completion date: November 16, 2017
• Est. primary completion date: November 16, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Pulmonary Fibrosis

Intervention

Drug:
• Pamrevlumab
Solution for infusion
• Placebo
Solution for infusion
• Sub-Study: Pirfenidone
Pirfenidone concomitant therapy will not be provided by the Sponsor.
• Sub-Study: Nintedanib
Nintedanib concomitant therapy will not be provided by the Sponsor.

Locations

Country	Name	City	State
Australia	Daw Park Repatriation	Adelaide	South Australia
Australia	Concord Repatriation	Concord	New South Wales
Bulgaria	MHAT 'Tokuda Hospital Sofia', AD, Department of Pulmonology	Sofia
Canada	Université de Sherbrooke / Hôpital Charles LeMoyne	Greenfield Park	Quebec
India	St Johns Medical College Hospital	Bangalore	Karnataka
India	Sri Bala Medical Centre and Hospital	Coimbatore	Tamil Nadu
India	Fortis Hospitals	Kolkata	West Bengal
India	Midland Healthcare & Research Center	Lucknow	Uttar Pradesh
India	Bhatia Hospital	Mumbai	Maharashtra
New Zealand	Christchurch Hospital NZ	Christchurch
New Zealand	Dunedin Public Hospital	Dunedin
New Zealand	Waikato Hospital	Hamilton
New Zealand	Tauranga Hospital	Tauranga
South Africa	Tygerberg Hospital Respiratory Research Unit	Cape Town	Western Cape
South Africa	Life Mount Edgecombe Hospital	Durban	KwaZulu-Natal
South Africa	Into Research	Pretoria	Gauteng
United States	Emory University	Atlanta	Georgia
United States	University of Maryland	Baltimore	Maryland
United States	The Kirklin Clinic	Birmingham	Alabama
United States	Steward St. Elizabeth's Medical Center	Boston	Massachusetts
United States	St. Luke's Hospital	Chesterfield	Missouri
United States	Northwestern University	Chicago	Illinois
United States	University of Cinncinati	Cincinnati	Ohio
United States	Vermont Lung Center	Colchester	Vermont
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	National Jewish Health	Denver	Colorado
United States	Henry Ford Medical Center	Detroit	Michigan
United States	PulmonIx LLC	Greensboro	North Carolina
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	Pulmonary Disease Specialist, PA	Kissimmee	Florida
United States	Dartmouth-Hitchcock Medical Center	Lebanon	Ohio
United States	David Geffen School of Medicine at UCLA	Los Angeles	California
United States	University of Louisville	Louisville	Kentucky
United States	Vanderbilt University	Nashville	Tennessee
United States	Yale University	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Pensacola Research Consultants, Inc., d.b.a. Avanza Medical Research Center	Pensacola	Florida
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Legacy Research Institute	Portland	Oregon
United States	UC Davis Medical Center	Sacramento	California
United States	University of Utah - Lung Health Research	Salt Lake City	Utah
United States	Via Christi Clinic, P.A.	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
FibroGen

Countries where clinical trial is conducted

United States,  Australia,  Bulgaria,  Canada,  India,  New Zealand,  South Africa, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in FVC (Percent of Predicted FVC Value [% Predicted]) to Week 48	FVC in liters was measured during the spirometry assessments at screening and during the randomized treatment period at Day 1 and every 12 weeks. The FVC (% predicted) was calculated for the corresponding gender-race-age group. The least squares (LS) mean change from Baseline to Week 48 (end of the randomized treatment period) in FVC (% predicted) is presented. Baseline was defined as the mean of the last screening visit and the Day 1 visit values. Other statistical analysis data is reported in the statistical analysis section. Observed data from all visits were included in the model.	Baseline (Screening and Day 1), Week 48
Secondary	Mean Change From Baseline in the HRCT Quantitative Lung Fibrosis (QLF) Score to Week 24 and Week 48	The extent of pulmonary fibrosis was measured by HRCT scans of the chest at screening and at Weeks 24 and 48, to determine the HRCT QLF score. Each lung was divided into 5 lobes (right upper, right middle, right lower, left upper, left lower). For the quantitative HRCT analyses, a computer read the images and quantified the percent (%) and volume (mL) of fibrosis for the whole lung by averaging the scores from each of 5 lung lobes. Baseline was defined as the Screening evaluation. Missing data were imputed using the multiple imputation (MI) method to handle missing values.	Baseline (Screening), Week 24 and Week 48
Secondary	Number of Participants With IPF Progression Events up to Week 48	IPF progression events included death from any cause or absolute decline in FVC (% predicted) value of =10%, confirmed by repeat spirometry. Classification of FVC (% predicted) declined =10% was based on observed and imputed data. Missing data in FVC (% predicted) were imputed using the predicted values from the random coefficient module with treatment, visit, visit-by-treatment interaction, and Baseline FVC (% predicted) as fixed effects and linear slope as random effect.	Baseline (Screening and Day 1) up to Week 48
Secondary	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	HRQoL was assessed by the SGRQ to measure health impairment, and includes 17 questions in 3 domains: Symptoms, Activity and Impacts. The domain and total scores range from 0 to 100, with 0 indicating the best and 100 indicating the worst possible health status. Missing data at post-baseline visits were imputed as the predicted values from the random coefficient model which included treatment, visit, visit-by-treatment interaction, and Baseline SGRQ score as fixed effects and linear slope of visit as random effect.	Baseline (Day 1), Week 24 and Week 48
Secondary	Number of Participants With a Respiratory-Related Hospitalization	Respiratory-related hospitalizations were reported by participants and recorded by the Investigators.	Week 55
Secondary	Number of Participants With a Respiratory-Related Death	Investigators determined whether a death was respiratory-related.	Week 55
Secondary	Number of Participants With No Decline in FVC (% Predicted) at Week 48	FVC in liters was measured during the spirometry assessments. The FVC (% predicted) was calculated for the corresponding gender-race-age group. Baseline was defined as the mean of the last screening visit and the Day 1 visit values. Classification of 'No decline' is based on observed and imputed data. Missing data in FVC (% predicted) are imputed using the predicted values from the random coefficient model with treatment, visit, visit-by-treatment interaction, and Baseline FVC (% predicted) as fixed effects and linear slope of visit as random effect.	Baseline (Day 1) to Week 48.