Efficacy and Safety of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis (IPF)

NCT01366209 — Phase 3, Completed, 555 participants, Genentech, Inc.

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A Randomized, Double-Blind, Placebo Controlled, Phase 3 Study of the Efficacy and Safety of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis (ASCEND Trial)

Registry	NCT01366209, acronym ASCEND
Status	Completed
Phase	Phase 3
Study type	Interventional; randomized, parallel, masking: quadruple, treatment
Enrollment	555 (Actual)
Sponsor	Genentech, Inc. (Industry)
Conditions	Idiopathic Pulmonary Fibrosis
Interventions	Pirfenidone, Placebo (Drug)
Dates	start 2011-06-01, primary completion 2014-02-01, completion 2014-02-01, first posted 2011-06-03, last updated 2017-04-05
Locations	1 site in United States

-Summary

PIPF-016 (ASCEND) is a Randomized, Double-Blind, Placebo Controlled, Phase 3 Study of the Efficacy and Safety of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. The study objectives are to confirm the treatment effect of pirfenidone compared with placebo on change in percent predicted forced vital capacity (%FVC) in patients with idiopathic pulmonary fibrosis (IPF), and to confirm the safety of treatment with pirfenidone compared with placebo in patients with IPF.

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+Arms and interventions

Arm	Type	Interventions	Description
Active Arm	Active comparator	Drug: Pirfenidone
Placebo Arm	Placebo comparator	Drug: Placebo

Pirfenidone (Drug): Pirfenidone, total daily dose of 2403 mg/ day, given as 3 divided doses 3 times per day.
Placebo (Drug): Placebo equivalent given as 3 divided doses 3 times per day.

+Outcome measures

Primary outcomes

Change in Percent Predicted Forced Vital Capacity (%FVC) From Baseline to Week 52 [52 weeks]

+Eligibility

Sex: All, ages: 40 Years to 80 Years

Select Inclusion Criteria:

1. Diagnosis of idiopathic pulmonary fibrosis (IPF), consistent with the ATS 2011 Guidelines, of 6-48 months' duration
2. Age 40 to 80 at randomization
3. Percent Forced Vital Capacity (%FVC) ≥50% and ≤90% at screening
4. Percent Carbon Monoxide Diffusing Capacity (%DLCO) ≥30% and ≤90% at screening

Select Exclusion Criteria:

1. Forced expiratory volume in one second (FEV1)/FVC ratio <0.8 after administration of bronchodilator at Screening
2. Expected to receive a lung transplant within 1 year from randomization or, for patients at sites in the United States, on a lung transplant waiting list at randomization
3. Known explanation for interstitial lung disease
4. History of asthma or chronic obstructive pulmonary disease
5. Active infection
6. Ongoing IPF treatments including investigational therapy, immunosuppressants, and cytokine modulating agents
7. History of unstable or deteriorating cardiac or pulmonary disease (other than IPF) within the previous 6 months

+Posted results

Participant flow

Milestone	Active Arm	Placebo Arm
Started	278	277
Completed	243	241
Not completed	35	36

Outcome results

Change in Percent Predicted Forced Vital Capacity (%FVC) From Baseline to Week 52 (Primary), Number, percentage of patients: Active Arm 16.5; Placebo Arm 31.8

Adverse events

Time frame: 1 year

Arm	Deaths	Serious adverse events	Other adverse events
Active Arm	0	55/278 (19.8%)	271/278 (97.5%)
Placebo Arm	0	69/277 (24.9%)	253/277 (91.3%)

Serious adverse events by term

Term	Organ system	Active Arm	Placebo Arm
Thrombocytopenia	Blood and lymphatic system disorders	1/278	0/277
Acute Myocardial Infarction	Cardiac disorders	1/278	1/277
Angina Pectoris	Cardiac disorders	3/278	0/277
Arrhythmia	Cardiac disorders	1/278	0/277
Atrial Fibrillation	Cardiac disorders	1/278	2/277
Atrial Flutter	Cardiac disorders	1/278	1/277
Atrioventricular Block	Cardiac disorders	0/278	1/277
Cardiac Arrest	Cardiac disorders	1/278	0/277
Cardiac Failure Congestive	Cardiac disorders	2/278	0/277
Cor Pulmonale	Cardiac disorders	0/278	1/277
Coronary Artery Occlusion	Cardiac disorders	0/278	1/277
Coronary Artery Disease	Cardiac disorders	1/278	1/277
Mitral Valve Incompetence	Cardiac disorders	1/278	0/277
Myocardial Infarction	Cardiac disorders	1/278	1/277
Myocardial Ischaemia	Cardiac disorders	1/278	0/277
Palpitations	Cardiac disorders	1/278	1/277
Sick Sinus Syndrome	Cardiac disorders	1/278	0/277
Tachycardia	Cardiac disorders	0/278	1/277
Abdominal Pain	Gastrointestinal disorders	1/278	0/277
Colitis Ulcerative	Gastrointestinal disorders	0/278	1/277
Duodenal Ulcer Haemorrhage	Gastrointestinal disorders	0/278	1/277
Gastrointestinal Haemorrhage	Gastrointestinal disorders	1/278	0/277
Ileus	Gastrointestinal disorders	1/278	0/277
Melaena	Gastrointestinal disorders	1/278	0/277
Nausea	Gastrointestinal disorders	3/278	0/277
Peptic Ulcer Haemorrhage	Gastrointestinal disorders	1/278	0/277
Umbilical Hernia Obstructive	Gastrointestinal disorders	1/278	0/277
Volvulus	Gastrointestinal disorders	1/278	0/277
Vomiting	Gastrointestinal disorders	1/278	0/277
Non-cardiac chest pain	General disorders	1/278	1/277
Hepatitis	Hepatobiliary disorders	1/278	0/277
Bronchitis	Infections and infestations	1/278	2/277
Bronchopneumonia	Infections and infestations	0/278	1/277
Clostridium difficile colitis	Infections and infestations	0/278	1/277
Gastroenteritis viral	Infections and infestations	0/278	2/277
Influenza	Infections and infestations	0/278	1/277
Lower respiratiory tract infection	Infections and infestations	1/278	0/277
Pneumonia mycoplasmal	Infections and infestations	0/278	1/277
Pneumonia respiratory syncytial viral	Infections and infestations	0/278	1/277
pneumonia	Infections and infestations	11/278	14/277
Pulmonary sepsis	Infections and infestations	0/278	1/277
Respiratory syncytial virus infection	Infections and infestations	0/278	1/277
Septic shock	Infections and infestations	1/278	2/277
Tracheobronchitis	Infections and infestations	0/278	1/277
Urinary tract infection	Infections and infestations	1/278	0/277
Viral upper respiratory tract infection	Infections and infestations	1/278	0/277
Ankle fracture	Injury, poisoning and procedural complications	1/278	0/277
Hand fracture	Injury, poisoning and procedural complications	1/278	0/277
Hip fracture	Injury, poisoning and procedural complications	0/278	1/277
Rib fracture	Injury, poisoning and procedural complications	2/278	0/277
Road traffic accident	Injury, poisoning and procedural complications	1/278	0/277
Traumatic brain injury	Injury, poisoning and procedural complications	1/278	0/277
Alanine aminotransferase increased	Investigations	1/278	0/277
Aspartate aminotransferase increased	Investigations	1/278	0/277
Weight decreased	Investigations	1/278	0/277
Dehydration	Metabolism and nutrition disorders	1/278	1/277
Diabetes Mellitus	Metabolism and nutrition disorders	0/278	1/277
Failure to thrive	Metabolism and nutrition disorders	0/278	1/277
Hyponatraemia	Metabolism and nutrition disorders	0/278	1/277
Arthritis	Musculoskeletal and connective tissue disorders	1/278	0/277

43 more terms not shown.

Other adverse events by term

Term	Organ system	Active Arm	Placebo Arm
Abdominal pain upper	Gastrointestinal disorders	20/278	12/277
Constipation	Gastrointestinal disorders	32/278	38/277
Diarrhoea	Gastrointestinal disorders	62/278	60/277
Dyspepsia	Gastrointestinal disorders	49/278	17/277
Flatulence	Gastrointestinal disorders	12/278	17/277
Gastrooesophageal Reflux	Gastrointestinal disorders	33/278	18/277
Nausea	Gastrointestinal disorders	100/278	37/277
Stomach Discomfort	Gastrointestinal disorders	24/278	12/277
Vomiting	Gastrointestinal disorders	36/278	24/277
Asthenia	General disorders	16/278	11/277
Oedema peripheral	General disorders	9/278	23/277
Pyrexia	General disorders	6/278	17/277
Bronchitis	Infections and infestations	38/278	34/277
Influenza	Infections and infestations	14/278	12/277
Lower respiratory tract infection	Infections and infestations	11/278	19/277
Nasopharyngitis	Infections and infestations	33/278	30/277
Sinusitis	Infections and infestations	20/278	24/277
Upper respiratory tract infection	Infections and infestations	61/278	56/277
Weight decreased	Investigations	35/278	22/277
Anorexia	Metabolism and nutrition disorders	44/278	18/277
Decreased appetite	Metabolism and nutrition disorders	20/278	10/277
Arthralgia	Musculoskeletal and connective tissue disorders	26/278	20/277
Back pain	Musculoskeletal and connective tissue disorders	30/278	37/277
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	14/278	9/277
Pain in extremity	Musculoskeletal and connective tissue disorders	14/278	16/277
Dizziness	Nervous system disorders	49/278	36/277
Dysgeusia	Nervous system disorders	25/278	11/277
Headache	Nervous system disorders	72/278	64/277
Anxiety	Psychiatric disorders	8/278	14/277
Depression	Psychiatric disorders	9/278	14/277
Insomnia	Psychiatric disorders	31/278	18/277
Cough	Respiratory, thoracic and mediastinal disorders	70/278	82/277
Dyspnoea	Respiratory, thoracic and mediastinal disorders	41/278	49/277
Idiopathic pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	19/278	32/277
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	14/278	20/277
Productive cough	Respiratory, thoracic and mediastinal disorders	9/278	14/277
Photosensitivity reaction	Skin and subcutaneous tissue disorders	16/278	1/277
Pruritis	Skin and subcutaneous tissue disorders	27/278	19/277
Rash	Skin and subcutaneous tissue disorders	78/278	24/277
Fatigue	General disorders	58/278	48/277
Urinary tract infection	Infections and infestations	8/278	17/277

+Locations (1)

Facility	City	Country	Status
InterMune Inc.	Brisbane, California	United States

+Publications

Results publication: Kulkarni T, Newton CA, Gupta S, Samara K, Bernstein EJ. The Impact of Autoantibodies on Outcomes in Patients with Idiopathic Pulmonary Fibrosis: Post-Hoc Analyses of the Phase III ASCEND Trial. Pulm Ther. 2024 Sep;10(3):331-346. doi: 10.1007/s41030-024-00267-x. Epub 2024 Jul 29. PMID 39073523
Results publication: Behr J, Nathan SD, Costabel U, Albera C, Wuyts WA, Glassberg MK, Haller H Jr, Alvaro G, Gilberg F, Samara K, Lancaster L. Efficacy and Safety of Pirfenidone in Advanced Versus Non-Advanced Idiopathic Pulmonary Fibrosis: Post-Hoc Analysis of Six Clinical Studies. Adv Ther. 2023 Sep;40(9):3937-3955. doi: 10.1007/s12325-023-02565-3. Epub 2023 Jun 30. PMID 37391667
Results publication: Allen RJ, Stockwell A, Oldham JM, Guillen-Guio B, Schwartz DA, Maher TM, Flores C, Noth I, Yaspan BL, Jenkins RG, Wain LV; International IPF Genetics Consortium. Genome-wide association study across five cohorts identifies five novel loci associated with idiopathic pulmonary fibrosis. Thorax. 2022 Aug;77(8):829-833. doi: 10.1136/thoraxjnl-2021-218577. Epub 2022 Jun 10. PMID 35688625
Results publication: Kreuter M, Lee JS, Tzouvelekis A, Oldham JM, Molyneaux PL, Weycker D, Atwood M, Kirchgaessler KU, Maher TM. Monocyte Count as a Prognostic Biomarker in Patients with Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2021 Jul 1;204(1):74-81. doi: 10.1164/rccm.202003-0669OC. PMID 33434107
Results publication: Glassberg MK, Nathan SD, Lin CY, Morgenthien EA, Stauffer JL, Chou W, Noble PW. Cardiovascular Risks, Bleeding Risks, and Clinical Events from 3 Phase III Trials of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis. Adv Ther. 2019 Oct;36(10):2910-2926. doi: 10.1007/s12325-019-01052-y. Epub 2019 Aug 10. PMID 31401786
Results publication: Nathan SD, Costabel U, Albera C, Behr J, Wuyts WA, Kirchgaessler KU, Stauffer JL, Morgenthien E, Chou W, Limb SL, Noble PW. Pirfenidone in patients with idiopathic pulmonary fibrosis and more advanced lung function impairment. Respir Med. 2019 Jul;153:44-51. doi: 10.1016/j.rmed.2019.04.016. Epub 2019 Apr 24. PMID 31153107
Results publication: Kreuter M, Lederer DJ, Molina-Molina M, Noth I, Valenzuela C, Frankenstein L, Weycker D, Atwood M, Kirchgaessler KU, Cottin V. Association of Angiotensin Modulators With the Course of Idiopathic Pulmonary Fibrosis. Chest. 2019 Oct;156(4):706-714. doi: 10.1016/j.chest.2019.04.015. Epub 2019 Apr 29. PMID 31047956
Results publication: Nathan SD, Costabel U, Glaspole I, Glassberg MK, Lancaster LH, Lederer DJ, Pereira CA, Trzaskoma B, Morgenthien EA, Limb SL, Wells AU. Efficacy of Pirfenidone in the Context of Multiple Disease Progression Events in Patients With Idiopathic Pulmonary Fibrosis. Chest. 2019 Apr;155(4):712-719. doi: 10.1016/j.chest.2018.11.008. Epub 2018 Nov 22. PMID 30472023
Results publication: Nathan SD, Lancaster LH, Albera C, Glassberg MK, Swigris JJ, Gilberg F, Kirchgaessler KU, Limb SL, Petzinger U, Noble PW. Dose modification and dose intensity during treatment with pirfenidone: analysis of pooled data from three multinational phase III trials. BMJ Open Respir Res. 2018 Aug 2;5(1):e000323. doi: 10.1136/bmjresp-2018-000323. eCollection 2018. PMID 30116539
Results publication: Neighbors M, Cabanski CR, Ramalingam TR, Sheng XR, Tew GW, Gu C, Jia G, Peng K, Ray JM, Ley B, Wolters PJ, Collard HR, Arron JR. Prognostic and predictive biomarkers for patients with idiopathic pulmonary fibrosis treated with pirfenidone: post-hoc assessment of the CAPACITY and ASCEND trials. Lancet Respir Med. 2018 Aug;6(8):615-626. doi: 10.1016/S2213-2600(18)30185-1. Epub 2018 Jun 29. PMID 30072107
Results publication: Paterniti MO, Bi Y, Rekic D, Wang Y, Karimi-Shah BA, Chowdhury BA. Acute Exacerbation and Decline in Forced Vital Capacity Are Associated with Increased Mortality in Idiopathic Pulmonary Fibrosis. Ann Am Thorac Soc. 2017 Sep;14(9):1395-1402. doi: 10.1513/AnnalsATS.201606-458OC. PMID 28388260
Results publication: Kreuter M, Bonella F, Maher TM, Costabel U, Spagnolo P, Weycker D, Kirchgaessler KU, Kolb M. Effect of statins on disease-related outcomes in patients with idiopathic pulmonary fibrosis. Thorax. 2017 Feb;72(2):148-153. doi: 10.1136/thoraxjnl-2016-208819. Epub 2016 Oct 5. PMID 27708114
Results publication: Nathan SD, Albera C, Bradford WZ, Costabel U, du Bois RM, Fagan EA, Fishman RS, Glaspole I, Glassberg MK, Glasscock KF, King TE Jr, Lancaster L, Lederer DJ, Lin Z, Pereira CA, Swigris JJ, Valeyre D, Noble PW, Wells AU. Effect of continued treatment with pirfenidone following clinically meaningful declines in forced vital capacity: analysis of data from three phase 3 trials in patients with idiopathic pulmonary fibrosis. Thorax. 2016 May;71(5):429-35. doi: 10.1136/thoraxjnl-2015-207011. Epub 2016 Mar 11. PMID 26968970
Results publication: Lancaster L, Albera C, Bradford WZ, Costabel U, du Bois RM, Fagan EA, Fishman RS, Glaspole I, Glassberg MK, King TE Jr, Lederer DJ, Lin Z, Nathan SD, Pereira CA, Swigris JJ, Valeyre D, Noble PW. Safety of pirfenidone in patients with idiopathic pulmonary fibrosis: integrated analysis of cumulative data from 5 clinical trials. BMJ Open Respir Res. 2016 Jan 12;3(1):e000105. doi: 10.1136/bmjresp-2015-000105. eCollection 2016. PMID 26835133
Results publication: Wijsenbeek MS, Grutters JC, Wuyts WA. Early Experience of Pirfenidone in Daily Clinical Practice in Belgium and The Netherlands: a Retrospective Cohort Analysis. Adv Ther. 2015 Jul;32(7):691-704. doi: 10.1007/s12325-015-0225-1. Epub 2015 Jul 15. PMID 26173796
Results publication: Lederer DJ, Bradford WZ, Fagan EA, Glaspole I, Glassberg MK, Glasscock KF, Kardatzke D, King TE Jr, Lancaster LH, Nathan SD, Pereira CA, Sahn SA, Swigris JJ, Noble PW. Sensitivity Analyses of the Change in FVC in a Phase 3 Trial of Pirfenidone for Idiopathic Pulmonary Fibrosis. Chest. 2015 Jul;148(1):196-201. doi: 10.1378/chest.14-2817. PMID 25856121
Results publication: King TE Jr, Bradford WZ, Castro-Bernardini S, Fagan EA, Glaspole I, Glassberg MK, Gorina E, Hopkins PM, Kardatzke D, Lancaster L, Lederer DJ, Nathan SD, Pereira CA, Sahn SA, Sussman R, Swigris JJ, Noble PW; ASCEND Study Group. A phase 3 trial of pirfenidone in patients with idiopathic pulmonary fibrosis. N Engl J Med. 2014 May 29;370(22):2083-92. doi: 10.1056/NEJMoa1402582. Epub 2014 May 18. PMID 24836312

+Investigators

For additional information, call InterMune Medical Information Telephone: 1-888-486-6411, Study chair, InterMune

My Notes

Public

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