Trial Outcomes & Findings for Long-Term Safety Study of GS-6624 in Adults With Idiopathic Pulmonary Fibrosis (IPF) (NCT NCT01759511)
NCT ID: NCT01759511
Last Updated: 2017-04-04
Results Overview
The overall safety of simtuzumab was assessed as the percentage of participants experiencing adverse events (AEs; Serious AEs, Grade 3 or 4 AEs, AEs related to simtuzumab, and AEs leading to discontinuation of simtuzumab), treatment-emergent chemistry and hematology abnormality.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
34 participants
Primary outcome timeframe
30 days post last study treatment (up to 165 weeks)
Results posted on
2017-04-04
Participant Flow
Participants were enrolled at 6 study sites in the United States. The first participant was screened on 18 October 2012. The last study visit occurred on 19 February 2016.
37 participants were screened.
Participant milestones
| Measure |
Simtuzumab
200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
|
|---|---|
|
Overall Study
STARTED
|
34
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
34
|
Reasons for withdrawal
| Measure |
Simtuzumab
200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
|
|---|---|
|
Overall Study
Adverse Event
|
4
|
|
Overall Study
Death
|
2
|
|
Overall Study
Lack of Efficacy
|
2
|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Progressive Disease
|
5
|
|
Overall Study
Protocol-Specified Criteria for Withdraw
|
4
|
|
Overall Study
Study Terminated by Sponsor
|
13
|
|
Overall Study
Withdrawal by Subject
|
3
|
Baseline Characteristics
Long-Term Safety Study of GS-6624 in Adults With Idiopathic Pulmonary Fibrosis (IPF)
Baseline characteristics by cohort
| Measure |
Simtuzumab
n=34 Participants
200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
|
|---|---|
|
Age, Continuous
|
67.9 years
STANDARD_DEVIATION 7.25 • n=5 Participants
|
|
Sex: Female, Male
Female
|
9 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
34 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
33 Participants
n=5 Participants
|
|
Forced vital capacity (FVC) Percent Predicted
|
69.9 FVC % predicted
STANDARD_DEVIATION 14.18 • n=5 Participants
|
|
FVC % Predicted Category
Mild
|
12 Participants
n=5 Participants
|
|
FVC % Predicted Category
Moderate
|
16 Participants
n=5 Participants
|
|
FVC % Predicted Category
Severe
|
6 Participants
n=5 Participants
|
|
Forced expirator volume in the first second of expiration (FEV1)/FVC Ratio
|
0.8 liter
STANDARD_DEVIATION 0.23 • n=5 Participants
|
|
Hemoglobin-Corrected Carbon dioxide diffusing capacity (DLCO) Predicted
|
12.2 DLCO % predicted
STANDARD_DEVIATION 4.22 • n=5 Participants
|
PRIMARY outcome
Timeframe: 30 days post last study treatment (up to 165 weeks)Population: Safety Analysis Set
The overall safety of simtuzumab was assessed as the percentage of participants experiencing adverse events (AEs; Serious AEs, Grade 3 or 4 AEs, AEs related to simtuzumab, and AEs leading to discontinuation of simtuzumab), treatment-emergent chemistry and hematology abnormality.
Outcome measures
| Measure |
Simtuzumab
n=34 Participants
200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
|
|---|---|
|
Overall Safety Profile of Simtuzumab
Adverse Events (AEs)
|
97.1 percentage of participants
|
|
Overall Safety Profile of Simtuzumab
Grade 3 or 4 AEs
|
47.1 percentage of participants
|
|
Overall Safety Profile of Simtuzumab
Serious Adverse Events
|
35.3 percentage of participants
|
|
Overall Safety Profile of Simtuzumab
SAEs Related to simtuzumab
|
5.9 percentage of participants
|
|
Overall Safety Profile of Simtuzumab
AEs leading to discontinuation of simtuzumab
|
29.4 percentage of participants
|
SECONDARY outcome
Timeframe: Weeks 72 and 144Population: Participants in Safety Analysis Set with available data were analyzed.
* FVC was a pulmonary function test, and was defined as the volume of air that can forcibly be blown out after taking a full breath. * Least square means were from mixed model for repeated measures (MMRM) model including baseline FVC % predicted and visit including all data up to Week 144.
Outcome measures
| Measure |
Simtuzumab
n=34 Participants
200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
|
|---|---|
|
Relative Change From Baseline in FVC % Predicted at Weeks 72 and 144
Week 72
|
-8.05 percent change in FVC % predicted
Standard Error 1.829
|
|
Relative Change From Baseline in FVC % Predicted at Weeks 72 and 144
Week 144
|
-12.04 percent change in FVC % predicted
Standard Error 2.086
|
SECONDARY outcome
Timeframe: Weeks 72 and 144Population: Participants in Safety Analysis Set with available data were analyzed.
* DLCO was a measurement to determine the extent to which oxygen passes from the air sacs of the lungs into the blood. * Least square means were from MMRM model including baseline DLCO % predicted and visit including all data up to Week 144.
Outcome measures
| Measure |
Simtuzumab
n=34 Participants
200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
|
|---|---|
|
Relative Change From Baseline in DLCO % Predicted at Weeks 72 and 144
Week 72
|
-7.41 percent change in DLCO % predicted
Standard Error 3.062
|
|
Relative Change From Baseline in DLCO % Predicted at Weeks 72 and 144
Week 144
|
-22.80 percent change in DLCO % predicted
Standard Error 3.475
|
SECONDARY outcome
Timeframe: Up to 165 weeksPopulation: Safety Analysis Set
All-cause mortality was assessed as a number of participants who died from any cause.
Outcome measures
| Measure |
Simtuzumab
n=34 Participants
200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
|
|---|---|
|
All-cause Mortality
|
3 Participants
|
SECONDARY outcome
Timeframe: Weeks 72 and 120Population: Participants in the Safety Analysis set with available data were analyzed.
Outcome measures
| Measure |
Simtuzumab
n=34 Participants
200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
|
|---|---|
|
Relative Change From Baseline in Serum Lysyl Oxidase-like 2 (sLOXL2) Levels at Weeks 72 and 120
Week 72
|
5.93 percent change in sLOXL2
Standard Error 5.937
|
|
Relative Change From Baseline in Serum Lysyl Oxidase-like 2 (sLOXL2) Levels at Weeks 72 and 120
Week 120
|
-0.69 percent change in sLOXL2
Standard Error 6.032
|
Adverse Events
Simtuzumab
Serious events: 12 serious events
Other events: 33 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Simtuzumab
n=34 participants at risk
200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
|
|---|---|
|
Blood and lymphatic system disorders
Leukocytosis
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Cardiac disorders
Coronary artery disease
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Cardiac disorders
Coronary artery occlusion
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Cardiac disorders
Myocardial infarction
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Gastrointestinal disorders
Hiatus hernia
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
General disorders
Chest pain
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Infections and infestations
Influenza
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Infections and infestations
Pneumonia
|
8.8%
3/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Infections and infestations
Urinary tract infection
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Chondrocalcinosis pyrophosphate
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Idiopathic pulmonary fibrosis
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Vascular disorders
Aortic stenosis
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Vascular disorders
Hypertension
|
2.9%
1/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
Other adverse events
| Measure |
Simtuzumab
n=34 participants at risk
200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
11.8%
4/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Cardiac disorders
Tachycardia
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Eye disorders
Cataract
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Eye disorders
Dry eye
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Gastrointestinal disorders
Abdominal discomfort
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Gastrointestinal disorders
Abdominal pain
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Gastrointestinal disorders
Abdominal pain upper
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Gastrointestinal disorders
Constipation
|
20.6%
7/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Gastrointestinal disorders
Diarrhoea
|
14.7%
5/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Gastrointestinal disorders
Flatulence
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Gastrointestinal disorders
Nausea
|
11.8%
4/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
General disorders
Chest discomfort
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
General disorders
Chest pain
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
General disorders
Chills
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
General disorders
Fatigue
|
29.4%
10/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
General disorders
Infusion site extravasation
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
General disorders
Injection site bruising
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
General disorders
Malaise
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
General disorders
Oedema peripheral
|
23.5%
8/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
General disorders
Pyrexia
|
8.8%
3/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Infections and infestations
Bronchitis
|
20.6%
7/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Infections and infestations
Gastroenteritis
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Infections and infestations
Influenza
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Infections and infestations
Nail infection
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Infections and infestations
Nasopharyngitis
|
11.8%
4/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Infections and infestations
Pneumonia
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Infections and infestations
Sinusitis
|
11.8%
4/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Infections and infestations
Upper respiratory tract infection
|
20.6%
7/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Infections and infestations
Urinary tract infection
|
8.8%
3/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Injury, poisoning and procedural complications
Fall
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Injury, poisoning and procedural complications
Laceration
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Injury, poisoning and procedural complications
Procedural pain
|
11.8%
4/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Investigations
Blood pressure increased
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Investigations
Gamma-glutamyltransferase increased
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Investigations
Occult blood positive
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Investigations
Weight decreased
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Metabolism and nutrition disorders
Decreased appetite
|
11.8%
4/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
8.8%
3/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
20.6%
7/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
14.7%
5/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
8.8%
3/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
14.7%
5/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
14.7%
5/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Nervous system disorders
Dizziness
|
14.7%
5/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Nervous system disorders
Headache
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Nervous system disorders
Syncope
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Psychiatric disorders
Anxiety
|
8.8%
3/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Psychiatric disorders
Depression
|
8.8%
3/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Psychiatric disorders
Mental status changes
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
52.9%
18/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
20.6%
7/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
14.7%
5/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
11.8%
4/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Idiopathic pulmonary fibrosis
|
8.8%
3/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
8.8%
3/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
17.6%
6/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
11.8%
4/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary mass
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
8.8%
3/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Respiratory, thoracic and mediastinal disorders
Upper-airway cough syndrome
|
8.8%
3/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Skin and subcutaneous tissue disorders
Precancerous skin lesion
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.9%
2/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
|
Skin and subcutaneous tissue disorders
Rash
|
14.7%
5/34 • 30 days post last study treatment (up to 165 weeks)
Safety Analysis Set
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: * The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or * The study has been completed at all study sites for at least 2 years
- Publication restrictions are in place
Restriction type: OTHER