Evaluate the Safety and Efficacy of FG-3019 in Patients With Idiopathic Pulmonary Fibrosis
Scientific Title of Study
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of FG-3019 in Patients with Idiopathic Pulmonary Fibrosis
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
FGCL-3019-067, Amendment 3.0 dated 28 May 2015
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Dr Saurendra Das
Designation
Executive Director
Affiliation
Excel Life Sciences Pvt Ltd
Address
Excel Life Sciences Pvt Ltd
D-62, First Floor, Sector 2, Noida-201301, Uttar Pradesh, India
Clinical Trial Ethics Committee G-1 Block, The Bhatia Hospital, Tardeo, Grant Road, Mumbai 400007, Maharashtra, India
Approved
Ethics Committee for Research Ethics Committee for Research Fortis Flt Lt Rajan Dhall Hospital Sector B, Pocket 1, Aruna Asaf Ali Marg, Vasant Kunj New Delhi – 110070, India
Approved
Ethics Committee Midland Healthcare & Research Centre B-55& C-42, Mandir Marg, Mahanagar, Lucknow-226006 Uttar Pradesh, India
Approved
Fortis Hospital Ethics Committee 730 Anandapur, Kolkata - 700107, West Bengal, India
Approved
Institutional Ethics Committee Delhi Heart & Lung Institute # 3, Mandir Marg II, Panchkuian Road, New Delhi-110055, India
Submittted/Under Review
Institutional Ethics Committee P.D. Hinduja National Hospital and Medical Research Centre Veer Savarkar Marg, Mahim, Mumbai – 400016, Maharashtra, India
Approved
Institutional Ethics Committee Prince Aly Khan Hospital Aga Hall, Nesbit Road, Mazagaon, Mumbai - 400010 Maharashtra, India
Institutional Human Ethics Committee Room No 104, Sri Bala Medical Centre and Hospital 901, Trichy Road, Ramanathauram Coimbatore – 641045, Tamil Nadu, India
Approved
KFRC Ethics Committee, KIMS Foundation and Research Center, #1-8-31/1, Minister Road, Secunderabad-500003, Telangana, India
Submittted/Under Review
NIMS Institutional Ethics Committee Nizam’s Institute of Medical Sciences Punjagutta, Hyderabad - 500082 Telengana, India
Submittted/Under Review
St Johns Medical College Institutional Ethics Committee Ground Floor St. Johns Medical College & Hospital Sarjapur Road, Bengaluru - 560034 Karnataka, India
FG-3019, Fully human recombinant IgG, kappa monoclonal anti-body
FG-3019, 30 mg/kg; 10 mg/ml, single dose vials, by intravenous infusion every 3 weeks for a total of 16 infusions over 45 weeks
Comparator Agent
Placebo
Sterile, clear aqueous solution, 10 mg/ml, single dose vials, by intravenous infusion every 3 weeks for a total of 16 infusions over 45 weeks
Inclusion Criteria
Age From
40.00 Year(s)
Age To
80.00 Year(s)
Gender
Both
Details
1. Age 40 to 80 years, inclusive.
2. Diagnosis of IPF as defined by current international guidelines (Raghu, 2011). Each subject must have one of the following: (1) Usual Interstitial Pneumonia (UIP) Pattern on an available HRCT scan; or (2) Possible UIP Pattern on an available HRCT scan and surgical lung biopsy within 4 years of Screening showing UIP Pattern (HRCT criteria for UIP Pattern and Possible UIP Pattern and histopathological criteria for UIP Pattern are described in protocol).
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 subjects of childbearing potential and male subjects with female partners of childbearing potential are required to use double barrier contraception methods during the conduct of the study and for 3 months after the last dose of study drug.
ExclusionCriteria
Details
1. Female subjects 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. History of other types of respiratory diseases including diseases or disorders of the airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall that, in the opinion of the Investigator, would impact the endpoints in the protocol or otherwise preclude the subject’s participation in the study.
7. History of any other respiratory, cardiovascular, renal, hepatic, metabolic, neurologic, hematologic, or other medical conditions that, in the opinion of the Investigator, would preclude the subject’s participation in the study.
8. Clinically important abnormal laboratory tests (including serum creatinine ≥1.5 x upper limit of normal [ULN], hemoglobin (Hb) <10 g/dL, white blood cells <3,000/mm3, platelets less than 100,000/mm3, serum total bilirubin >1.5 x ULN, serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥2 x ULN, or serum alkaline phosphatase ≥2 x ULN.
9. Upper or lower respiratory tract infection of any type within 4 weeks of Screening.
10. Acute exacerbation of IPF within 3 months of Screening.
11. Evidence of obstructive lung disease by any of the following criteria: forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio <0.70 or extent of emphysema on HRCT greater than the extent of fibrosis on HRCT.
12. DLCO <30% of predicted value.
13. High likelihood of lung transplantation (in the opinion of the Investigator) within 6 months after Day 1.
14. Poorly controlled chronic heart failure; clinical diagnosis of cor pulmonale requiring specific treatment; or severe pulmonary hypertension requiring specific treatment that, in the opinion of the Investigator, would preclude the subject’s participation in the study.
15. 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.
16. Use of any investigational drugs, including any investigational drugs for IPF, within 4 weeks prior to Day 1 dosing.
17. 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.
18. Clinically significant trauma or surgical procedures within 4 weeks prior to dosing.
19. Planned elective surgery during the study including 4 weeks following the final dose of Study Drug.
20. History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies.
21. The Investigator judges that the subject will be unable to fully participate in the study and complete it for any reason, including inability to comply with study procedures and treatment, addiction, or any other relevant medical or psychiatric conditions.
22. Body weight >130 kg.
23. Previous treatment with FG-3019.
24. Inadequate IV access.
Method of Generating Random Sequence
Stratified randomization
Method of Concealment
Centralized
Blinding/Masking
Participant and Investigator Blinded
Primary Outcome
Outcome
TimePoints
Change from baseline in FVC (percent of predicted value) at Week 48
Day 1 to Week 48
Secondary Outcome
Outcome
TimePoints
1. To evaluate the effect of FG-3019 on the extent of pulmonary fibrosis as measured by high resolution computed tomography (HRCT) scans of the chest
2. To evaluate the relationship between changes in quantified scores of pulmonary fibrosis and clinical outcomes
3. To evaluate the effect of FG-3019 on progression of IPF and the frequency of respiratory-related hospitalizations and respiratory-related mortality
4. To evaluate the effect of FG-3019 on health-related quality of life (HRQoL)
1. Week 24 and Week 48 and later time points
2. Week 48
3. Week 52
4. Week 24 and Week 48 and later time points
Target Sample Size
Total Sample Size="136" Sample Size from India="55" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
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.
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Brief Summary
This is a Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of FG-3019 in Patients with Idiopathic Pulmonary Fibrosis. The study will enroll Male or female subjects, 40 to 80, years old who have IPF diagnosed in accordance with criteria published in the 2011 international consensus guidelines. Subjects who have failed or are intolerant of products approved for treating IPF are eligible. Approximately 136 patients will be enrolled across multiple sites globally. Subjects who sign informed consent will undergo screening visits to determine their eligibility. Eligible subjects who provide written informed consent will be stratified based on prior therapy with nintedanib and/or pirfenidone (yes/no) and randomized (1:1) to one of two treatment arms.
Study Drug (FG-3019 [30 mg/kg] or placebo) will be administered by IV infusion every 3 weeks for a total of 16 infusions over 48 weeks. Patients will be evaluated at 48 weeks following which they will be provided access to extended treatment phase for 48 weeks or until the patients FVC percent predicted decreases 3% or more on two consecutive scheduled evaluations.