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

• Sponsor: Genentech, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01366209
• Collaborator: (none)
• Enrollment: 555
• Location: 1
• Arms: 2
• Duration (Months): 32.1
• Patients Per Site Per Month: 17.3

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Pulmonary Fibrosis	Drug: Pirfenidone; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 555 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo Controlled, Phase 3 Study of the Efficacy and Safety of Pirfenidone in Patients With Idiopathic Pulmonary Fibrosis (ASCEND Trial)
• Study Start Date: Jun 1, 2011
• Actual Primary Completion Date: Feb 1, 2014
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Active Arm	Drug: Pirfenidone; Pirfenidone, total daily dose of 2403 mg/ day, given as 3 divided doses 3 times per day.
Placebo Comparator: Placebo Arm	Drug: Placebo; Placebo equivalent given as 3 divided doses 3 times per day.

Outcome Measures

Primary Outcome Measures

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	InterMune Inc.	Brisbane	California	United States	94005

Sponsors and Collaborators

• Genentech, Inc.

Investigators

• Study Chair: For additional information, call InterMune Medical Information Telephone: [phone], InterMune

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT01366209
• Other Study ID Numbers: PIPF-016
• First Posted: Jun 3, 2011
• Last Update Posted: Apr 5, 2017
• Last Verified: Mar 1, 2017

• Keywords provided by Genentech, Inc.: Pirfenidone; ASCEND; IPF; FVC
• Additional relevant MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis; Pirfenidone

Study Results

Participant Flow

Arm/Group Title	Active Arm	Placebo Arm
Arm/Group Description	Pirfenidone: Pirfenidone, total daily dose of 2403 mg/ day, given as 3 divided doses 3 times per day.	Placebo: Placebo equivalent given as 3 divided doses 3 times per day.
Period Title: Overall Study
STARTED	278	277
COMPLETED	243	241
NOT COMPLETED	35	36

Baseline Characteristics

Arm/Group Title	Active Arm	Placebo Arm	Total
Arm/Group Description	Pirfenidone: Pirfenidone, total daily dose of 2403 mg/ day, given as 3 divided doses 3 times per day.	Placebo: Placebo equivalent given as 3 divided doses 3 times per day.	Total of all reporting groups
Overall Participants	278	277	555
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	73 26.3%	88 31.8%	161 29%
>=65 years	205 73.7%	189 68.2%	394 71%
Sex: Female, Male (Count of Participants)
Female	56 20.1%	64 23.1%	120 21.6%
Male	222 79.9%	213 76.9%	435 78.4%
Region of Enrollment (participants) [Number]
United States	187 67.3%	184 66.4%	371 66.8%
Australia	33 11.9%	31 11.2%	64 11.5%
Brazil	15 5.4%	16 5.8%	31 5.6%
Croatia	1 0.4%	1 0.4%	2 0.4%
Israel	11 4%	9 3.2%	20 3.6%
Mexico	12 4.3%	5 1.8%	17 3.1%
New Zealand	1 0.4%	3 1.1%	4 0.7%
Peru	18 6.5%	26 9.4%	44 7.9%
Singapore	0 0%	2 0.7%	2 0.4%

Outcome Measures

1. Primary Outcome

Title	Change in Percent Predicted Forced Vital Capacity (%FVC) From Baseline to Week 52
Time Frame	52 weeks

Outcome Measure Data

Analysis Population Description

Intent to Treat all randomized Patient

Arm/Group Title	Active Arm	Placebo Arm
Arm/Group Description	Pirfenidone: Pirfenidone, total daily dose of 2403 mg/ day, given as 3 divided doses 3 times per day.	Placebo: Placebo equivalent given as 3 divided doses 3 times per day.
Measure Participants	278	277
Decline or >=10% or Death	16.5	31.8
No Decline (Change >0%)	22.7	9.7

Adverse Events

Time Frame	1 year
Arm/Group Title	Active Arm		Placebo Arm
Arm/Group Description	Pirfenidone: Pirfenidone, total daily dose of 2403 mg/ day, given as 3 divided doses 3 times per day.		Placebo: Placebo equivalent given as 3 divided doses 3 times per day.
All Cause Mortality
	Active Arm		Placebo Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Active Arm		Placebo Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	55/278 (19.8%)		69/277 (24.9%)
Blood and lymphatic system disorders
Thrombocytopenia	1/278 (0.4%)	1	0/277 (0%)	0
Cardiac disorders
Acute Myocardial Infarction	1/278 (0.4%)	2	1/277 (0.4%)	1
Angina Pectoris	3/278 (1.1%)	4	0/277 (0%)	0
Arrhythmia	1/278 (0.4%)	1	0/277 (0%)	0
Atrial Fibrillation	1/278 (0.4%)	1	2/277 (0.7%)	2
Atrial Flutter	1/278 (0.4%)	1	1/277 (0.4%)	1
Atrioventricular Block	0/278 (0%)	0	1/277 (0.4%)	1
Cardiac Arrest	1/278 (0.4%)	1	0/277 (0%)	0
Cardiac Failure Congestive	2/278 (0.7%)	2	0/277 (0%)	0
Cor Pulmonale	0/278 (0%)	0	1/277 (0.4%)	1
Coronary Artery Occlusion	0/278 (0%)	0	1/277 (0.4%)	1
Coronary Artery Disease	1/278 (0.4%)	1	1/277 (0.4%)	1
Mitral Valve Incompetence	1/278 (0.4%)	1	0/277 (0%)	0
Myocardial Infarction	1/278 (0.4%)	1	1/277 (0.4%)	1
Myocardial Ischaemia	1/278 (0.4%)	1	0/277 (0%)	0
Palpitations	1/278 (0.4%)	1	1/277 (0.4%)	1
Sick Sinus Syndrome	1/278 (0.4%)	1	0/277 (0%)	0
Tachycardia	0/278 (0%)	0	1/277 (0.4%)	1
Gastrointestinal disorders
Abdominal Pain	1/278 (0.4%)	1	0/277 (0%)	0
Colitis Ulcerative	0/278 (0%)	0	1/277 (0.4%)	1
Duodenal Ulcer Haemorrhage	0/278 (0%)	0	1/277 (0.4%)	1
Gastrointestinal Haemorrhage	1/278 (0.4%)	1	0/277 (0%)	0
Ileus	1/278 (0.4%)	1	0/277 (0%)	0
Melaena	1/278 (0.4%)	1	0/277 (0%)	0
Nausea	3/278 (1.1%)	3	0/277 (0%)	0
Peptic Ulcer Haemorrhage	1/278 (0.4%)	1	0/277 (0%)	0
Umbilical Hernia Obstructive	1/278 (0.4%)	1	0/277 (0%)	0
Volvulus	1/278 (0.4%)	1	0/277 (0%)	0
Vomiting	1/278 (0.4%)	1	0/277 (0%)	0
General disorders
Non-cardiac chest pain	1/278 (0.4%)	1	1/277 (0.4%)	1
Hepatobiliary disorders
Hepatitis	1/278 (0.4%)	1	0/277 (0%)	0
Infections and infestations
Bronchitis	1/278 (0.4%)	1	2/277 (0.7%)	2
Bronchopneumonia	0/278 (0%)	0	1/277 (0.4%)	1
Clostridium difficile colitis	0/278 (0%)	0	1/277 (0.4%)	1
Gastroenteritis viral	0/278 (0%)	0	2/277 (0.7%)	2
Influenza	0/278 (0%)	0	1/277 (0.4%)	1
Lower respiratiory tract infection	1/278 (0.4%)	1	0/277 (0%)	0
Pneumonia mycoplasmal	0/278 (0%)	0	1/277 (0.4%)	1
Pneumonia respiratory syncytial viral	0/278 (0%)	0	1/277 (0.4%)	1
pneumonia	11/278 (4%)	11	14/277 (5.1%)	16
Pulmonary sepsis	0/278 (0%)	0	1/277 (0.4%)	1
Respiratory syncytial virus infection	0/278 (0%)	0	1/277 (0.4%)	1
Septic shock	1/278 (0.4%)	1	2/277 (0.7%)	2
Tracheobronchitis	0/278 (0%)	0	1/277 (0.4%)	1
Urinary tract infection	1/278 (0.4%)	1	0/277 (0%)	0
Viral upper respiratory tract infection	1/278 (0.4%)	1	0/277 (0%)	0
Injury, poisoning and procedural complications
Ankle fracture	1/278 (0.4%)	1	0/277 (0%)	0
Hand fracture	1/278 (0.4%)	1	0/277 (0%)	0
Hip fracture	0/278 (0%)	0	1/277 (0.4%)	1
Rib fracture	2/278 (0.7%)	2	0/277 (0%)	0
Road traffic accident	1/278 (0.4%)	1	0/277 (0%)	0
Traumatic brain injury	1/278 (0.4%)	1	0/277 (0%)	0
Investigations
Alanine aminotransferase increased	1/278 (0.4%)	1	0/277 (0%)	0
Aspartate aminotransferase increased	1/278 (0.4%)	1	0/277 (0%)	0
Weight decreased	1/278 (0.4%)	1	0/277 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/278 (0.4%)	1	1/277 (0.4%)	1
Diabetes Mellitus	0/278 (0%)	0	1/277 (0.4%)	1
Failure to thrive	0/278 (0%)	0	1/277 (0.4%)	1
Hyponatraemia	0/278 (0%)	0	1/277 (0.4%)	1
Musculoskeletal and connective tissue disorders
Arthritis	1/278 (0.4%)	1	0/277 (0%)	0
Cervical spinal stenosis	1/278 (0.4%)	1	0/277 (0%)	0
Intervertebral disc degeneration	0/278 (0%)	0	1/277 (0.4%)	1
Intervertebral disc protrusion	1/278 (0.4%)	1	0/277 (0%)	0
Musculoskeletal chest pain	1/278 (0.4%)	1	1/277 (0.4%)	1
Osteoarthritis	1/278 (0.4%)	1	0/277 (0%)	0
Pain in jaw	0/278 (0%)	0	1/277 (0.4%)	1
Rotator cuff syndrome	1/278 (0.4%)	1	0/277 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer in situ	0/278 (0%)	0	1/277 (0.4%)	1
Breast cancer	0/278 (0%)	0	1/277 (0.4%)	1
Gastric cancer	1/278 (0.4%)	1	0/277 (0%)	0
Hepatic neoplasm malignant	1/278 (0.4%)	1	0/277 (0%)	0
Hypopharyngeal cancer	1/278 (0.4%)	1	0/277 (0%)	0
Prostate cancer	2/278 (0.7%)	2	4/277 (1.4%)	4
Nervous system disorders
Cerebrovascular Accident	0/278 (0%)	0	1/277 (0.4%)	1
Haemorrhage intercranial	0/278 (0%)	0	1/277 (0.4%)	1
Haemorrhagic stroke	0/278 (0%)	0	1/277 (0.4%)	1
Ischaemic stroke	1/278 (0.4%)	1	0/277 (0%)	0
IVth nerve paralysis	0/278 (0%)	0	1/277 (0.4%)	1
Loss of consciousness	0/278 (0%)	0	1/277 (0.4%)	1
Spinal cord compression	1/278 (0.4%)	1	0/277 (0%)	0
Syncope	1/278 (0.4%)	1	1/277 (0.4%)	1
Psychiatric disorders
Completed suicide	0/278 (0%)	0	1/277 (0.4%)	1
Psychotic disorder	1/278 (0.4%)	1	0/277 (0%)	0
Renal and urinary disorders
Renal failure acute	0/278 (0%)	0	1/277 (0.4%)	1
Renal failure	1/278 (0.4%)	1	1/277 (0.4%)	1
Urethral pain	1/278 (0.4%)	1	0/277 (0%)	0
Urinary retention	1/278 (0.4%)	1	0/277 (0%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/278 (0.4%)	1	0/277 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/278 (0.4%)	1	1/277 (0.4%)	1
Cough	1/278 (0.4%)	1	0/277 (0%)	0
Dyspnoea	1/278 (0.4%)	1	2/277 (0.7%)	2
Hypoxia	1/278 (0.4%)	1	0/277 (0%)	0
Idiopathic pulmonary fibrosis	7/278 (2.5%)	11	27/277 (9.7%)	32
Interstitial lung disease	1/278 (0.4%)	1	0/277 (0%)	0
Pneumothorax spontaneous tension	0/278 (0%)	0	1/277 (0.4%)	1
Pneumothorax	1/278 (0.4%)	1	1/277 (0.4%)	1
Pulmonary alveolar haemorrhage	0/278 (0%)	0	1/277 (0.4%)	1
Pulmonary embolism	1/278 (0.4%)	1	2/277 (0.7%)	2
Respiratory failure	1/278 (0.4%)	1	1/277 (0.4%)	1
Pulmonary Hypertension	1/278 (0.4%)		1/277 (0.4%)
Vascular disorders
Aortic aneurysm	0/278 (0%)	0	2/277 (0.7%)	2
Deep vein thrombosis	0/278 (0%)	0	1/277 (0.4%)	1
Hypotension	0/278 (0%)	0	1/277 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Active Arm		Placebo Arm
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	271/278 (97.5%)		253/277 (91.3%)
Gastrointestinal disorders
Abdominal pain upper	20/278 (7.2%)	33	12/277 (4.3%)	14
Constipation	32/278 (11.5%)	38	38/277 (13.7%)	39
Diarrhoea	62/278 (22.3%)	112	60/277 (21.7%)	101
Dyspepsia	49/278 (17.6%)	61	17/277 (6.1%)	22
Flatulence	12/278 (4.3%)	13	17/277 (6.1%)	18
Gastrooesophageal Reflux	33/278 (11.9%)	36	18/277 (6.5%)	21
Nausea	100/278 (36%)	138	37/277 (13.4%)	46
Stomach Discomfort	24/278 (8.6%)	38	12/277 (4.3%)	15
Vomiting	36/278 (12.9%)	74	24/277 (8.7%)	28
General disorders
Asthenia	16/278 (5.8%)	17	11/277 (4%)	12
Oedema peripheral	9/278 (3.2%)	9	23/277 (8.3%)	24
Pyrexia	6/278 (2.2%)	7	17/277 (6.1%)	20
Fatigue	58/278 (20.9%)	93	48/277 (17.3%)	55
Infections and infestations
Bronchitis	38/278 (13.7%)	50	34/277 (12.3%)	49
Influenza	14/278 (5%)	16	12/277 (4.3%)	12
Lower respiratory tract infection	11/278 (4%)	13	19/277 (6.9%)	23
Nasopharyngitis	33/278 (11.9%)	45	30/277 (10.8%)	40
Sinusitis	20/278 (7.2%)	25	24/277 (8.7%)	32
Upper respiratory tract infection	61/278 (21.9%)	78	56/277 (20.2%)	79
Urinary tract infection	8/278 (2.9%)	12	17/277 (6.1%)	28
Investigations
Weight decreased	35/278 (12.6%)	35	22/277 (7.9%)	23
Metabolism and nutrition disorders
Anorexia	44/278 (15.8%)	47	18/277 (6.5%)	19
Decreased appetite	20/278 (7.2%)	23	10/277 (3.6%)	10
Musculoskeletal and connective tissue disorders
Arthralgia	26/278 (9.4%)	36	20/277 (7.2%)	33
Back pain	30/278 (10.8%)	35	37/277 (13.4%)	42
Musculoskeletal pain	14/278 (5%)	14	9/277 (3.2%)	11
Pain in extremity	14/278 (5%)	18	16/277 (5.8%)	18
Nervous system disorders
Dizziness	49/278 (17.6%)	88	36/277 (13%)	43
Dysgeusia	25/278 (9%)	26	11/277 (4%)	12
Headache	72/278 (25.9%)	117	64/277 (23.1%)	96
Psychiatric disorders
Anxiety	8/278 (2.9%)	8	14/277 (5.1%)	14
Depression	9/278 (3.2%)	9	14/277 (5.1%)	14
Insomnia	31/278 (11.2%)	33	18/277 (6.5%)	21
Respiratory, thoracic and mediastinal disorders
Cough	70/278 (25.2%)	104	82/277 (29.6%)	97
Dyspnoea	41/278 (14.7%)	49	49/277 (17.7%)	66
Idiopathic pulmonary fibrosis	19/278 (6.8%)	21	32/277 (11.6%)	43
Pharyngolaryngeal pain	14/278 (5%)	14	20/277 (7.2%)	21
Productive cough	9/278 (3.2%)	11	14/277 (5.1%)	14
Skin and subcutaneous tissue disorders
Photosensitivity reaction	16/278 (5.8%)	25	1/277 (0.4%)	1
Pruritis	27/278 (9.7%)	35	19/277 (6.9%)	20
Rash	78/278 (28.1%)	123	24/277 (8.7%)	27

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.