ATLAS: Long-Term Safety Study of GS-6624 in Adults With Idiopathic Pulmonary Fibrosis (IPF)

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01759511
• Collaborator: (none)
• Enrollment: 34
• Locations: 6
• Arm: 1
• Actual Duration (Months): 40
• Patients Per Site: 5.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the long term safety and tolerability of simtuzumab (GS-6624) in participants with idiopathic pulmonary fibrosis (IPF) who had previously participated in Gilead clinical trial AB0024-201.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Pulmonary Fibrosis	Drug: Simtuzumab	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Long-Term Safety Study of GS-6624 in Adult Subjects With Idiopathic Pulmonary Fibrosis (IPF)
• Actual Study Start Date: Oct 18, 2012
• Actual Primary Completion Date: Feb 19, 2016
• Actual Study Completion Date: Feb 19, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Simtuzumab Participants will receive simtuzumab.	Drug: 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); Other Names: GS-6624

Outcome Measures

Primary Outcome Measures

1. Overall Safety Profile of Simtuzumab [30 days post last study treatment (up to 165 weeks)]

   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.

Secondary Outcome Measures

1. Relative Change From Baseline in FVC % Predicted at Weeks 72 and 144 [Weeks 72 and 144]

   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.

2. Relative Change From Baseline in DLCO % Predicted at Weeks 72 and 144 [Weeks 72 and 144]

   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.

3. All-cause Mortality [Up to 165 weeks]

   All-cause mortality was assessed as a number of participants who died from any cause.

4. Relative Change From Baseline in Serum Lysyl Oxidase-like 2 (sLOXL2) Levels at Weeks 72 and 120 [Weeks 72 and 120]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Previous participation in Phase 1 Gilead clinical trial

• Diagnosis of idiopathic pulmonary fibrosis

• Females of childbearing potential and non-vasectomized males must agree to use highly effective methods of contraception

• Females must discontinue nursing

• Comply with study requirements

• Have adequate organ function

Key Exclusion Criteria:

• History or evidence of clinically significant disorder, condition or disease that would pose a risk or interfere with the study

• Pregnant or lactating

• Clinically significant heart, hepatic or renal disease

• History of cancer within 5 years of screening

• Infection that is not controlled despite antibiotics or other treatment

• History of bleeding diathesis within the last 6 months of Day 1

• Known history of human immunodeficiency virus, hepatitis B or C

• Concern's for subjects compliance

• Other conditions that might put the subject at high risk for treatment complications or reduce the chance to obtain data required

• Placed on a lung transplant list

• Previous participation in an idiopathic pulmonary fibrosis clinical trial other than for simtuzumab

Note: Other protocol defined Inclusion/Exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arizona Pulmonary Specialists, Ltd.	Scottsdale	Arizona	United States	85012
2	University of California	Los Angeles	California	United States	90095
3	Stanford University Medical Center	Stanford	California	United States	94305
4	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
5	Medical University of South Carolina	Charleston	South Carolina	United States	29425
6	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01759511
• Other Study ID Numbers: GS-US-322-0206
• First Posted: Jan 3, 2013
• Last Update Posted: Apr 4, 2017
• Last Verified: Feb 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Gilead Sciences: Idiopathic; Pulmonary; Fibrosis; IPF
• Additional relevant MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis

Study Results

Participant Flow

Recruitment Details	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.
Pre-assignment Detail	37 participants were screened.

Arm/Group Title	Simtuzumab
Arm/Group Description	200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
Period Title: Overall Study
STARTED	34
COMPLETED	0
NOT COMPLETED	34

Baseline Characteristics

Arm/Group Title	Simtuzumab
Arm/Group Description	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 Participants	34
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	67.9 (7.25)
Sex: Female, Male (Count of Participants)
Female	9 26.5%
Male	25 73.5%
Race/Ethnicity, Customized (Count of Participants)
White	34 100%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	1 2.9%
Not Hispanic or Latino	33 97.1%
Forced vital capacity (FVC) Percent Predicted (FVC % predicted) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [FVC % predicted]	69.9 (14.18)
FVC % Predicted Category (Count of Participants)
Mild	12 35.3%
Moderate	16 47.1%
Severe	6 17.6%
Forced expirator volume in the first second of expiration (FEV1)/FVC Ratio (liter) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [liter]	0.8 (0.23)
Hemoglobin-Corrected Carbon dioxide diffusing capacity (DLCO) Predicted (DLCO % predicted) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [DLCO % predicted]	12.2 (4.22)

Outcome Measures

1. Primary Outcome

Title	Overall Safety Profile of Simtuzumab
Description	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.
Time Frame	30 days post last study treatment (up to 165 weeks)

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Simtuzumab
Arm/Group Description	200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
Measure Participants	34
Adverse Events (AEs)	97.1 285.6%
Grade 3 or 4 AEs	47.1 138.5%
Serious Adverse Events	35.3 103.8%
SAEs Related to simtuzumab	5.9 17.4%
AEs leading to discontinuation of simtuzumab	29.4 86.5%

2. Secondary Outcome

Title	Relative Change From Baseline in FVC % Predicted at Weeks 72 and 144
Description	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.
Time Frame	Weeks 72 and 144

Outcome Measure Data

Analysis Population Description

Participants in Safety Analysis Set with available data were analyzed.

Arm/Group Title	Simtuzumab
Arm/Group Description	200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
Measure Participants	34
Week 72	-8.05 (1.829)
Week 144	-12.04 (2.086)

3. Secondary Outcome

Title	Relative Change From Baseline in DLCO % Predicted at Weeks 72 and 144
Description	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.
Time Frame	Weeks 72 and 144

Outcome Measure Data

Analysis Population Description

Participants in Safety Analysis Set with available data were analyzed.

Arm/Group Title	Simtuzumab
Arm/Group Description	200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
Measure Participants	34
Week 72	-7.41 (3.062)
Week 144	-22.80 (3.475)

4. Secondary Outcome

Title	All-cause Mortality
Description	All-cause mortality was assessed as a number of participants who died from any cause.
Time Frame	Up to 165 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	Simtuzumab
Arm/Group Description	200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
Measure Participants	34
Count of Participants [Participants]	3 8.8%

5. Secondary Outcome

Title	Relative Change From Baseline in Serum Lysyl Oxidase-like 2 (sLOXL2) Levels at Weeks 72 and 120
Time Frame	Weeks 72 and 120

Outcome Measure Data

Analysis Population Description

Participants in the Safety Analysis set with available data were analyzed.

Arm/Group Title	Simtuzumab
Arm/Group Description	200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
Measure Participants	34
Week 72	5.93 (5.937)
Week 120	-0.69 (6.032)

Adverse Events

Time Frame	30 days post last study treatment (up to 165 weeks)
Adverse Event Reporting Description	Safety Analysis Set
Arm/Group Title	Simtuzumab
Arm/Group Description	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
	Simtuzumab
	Affected / at Risk (%)	# Events
Total	3/34 (8.8%)
Serious Adverse Events
	Simtuzumab
	Affected / at Risk (%)	# Events
Total	12/34 (35.3%)
Blood and lymphatic system disorders
Leukocytosis	1/34 (2.9%)
Cardiac disorders
Arteriosclerosis coronary artery	1/34 (2.9%)
Coronary artery disease	1/34 (2.9%)
Coronary artery occlusion	1/34 (2.9%)
Myocardial infarction	1/34 (2.9%)
Gastrointestinal disorders
Hiatus hernia	1/34 (2.9%)
General disorders
Chest pain	1/34 (2.9%)
Infections and infestations
Influenza	1/34 (2.9%)
Pneumonia	3/34 (8.8%)
Urinary tract infection	1/34 (2.9%)
Musculoskeletal and connective tissue disorders
Chondrocalcinosis pyrophosphate	1/34 (2.9%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma	1/34 (2.9%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	2/34 (5.9%)
Dyspnoea	1/34 (2.9%)
Idiopathic pulmonary fibrosis	1/34 (2.9%)
Pneumothorax	1/34 (2.9%)
Pulmonary fibrosis	1/34 (2.9%)
Respiratory failure	1/34 (2.9%)
Vascular disorders
Aortic stenosis	1/34 (2.9%)
Hypertension	1/34 (2.9%)
Other (Not Including Serious) Adverse Events
	Simtuzumab
	Affected / at Risk (%)	# Events
Total	33/34 (97.1%)
Blood and lymphatic system disorders
Anaemia	4/34 (11.8%)
Cardiac disorders
Tachycardia	2/34 (5.9%)
Eye disorders
Cataract	2/34 (5.9%)
Dry eye	2/34 (5.9%)
Gastrointestinal disorders
Abdominal discomfort	2/34 (5.9%)
Abdominal pain	2/34 (5.9%)
Abdominal pain upper	2/34 (5.9%)
Constipation	7/34 (20.6%)
Diarrhoea	5/34 (14.7%)
Flatulence	2/34 (5.9%)
Nausea	4/34 (11.8%)
General disorders
Chest discomfort	2/34 (5.9%)
Chest pain	2/34 (5.9%)
Chills	2/34 (5.9%)
Fatigue	10/34 (29.4%)
Infusion site extravasation	2/34 (5.9%)
Injection site bruising	2/34 (5.9%)
Malaise	2/34 (5.9%)
Oedema peripheral	8/34 (23.5%)
Pyrexia	3/34 (8.8%)
Infections and infestations
Bronchitis	7/34 (20.6%)
Gastroenteritis	2/34 (5.9%)
Influenza	2/34 (5.9%)
Nail infection	2/34 (5.9%)
Nasopharyngitis	4/34 (11.8%)
Pneumonia	2/34 (5.9%)
Sinusitis	4/34 (11.8%)
Upper respiratory tract infection	7/34 (20.6%)
Urinary tract infection	3/34 (8.8%)
Injury, poisoning and procedural complications
Fall	2/34 (5.9%)
Laceration	2/34 (5.9%)
Procedural pain	4/34 (11.8%)
Investigations
Blood pressure increased	2/34 (5.9%)
Gamma-glutamyltransferase increased	2/34 (5.9%)
Occult blood positive	2/34 (5.9%)
Weight decreased	2/34 (5.9%)
Metabolism and nutrition disorders
Decreased appetite	4/34 (11.8%)
Hypokalaemia	2/34 (5.9%)
Hyponatraemia	3/34 (8.8%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/34 (20.6%)
Back pain	5/34 (14.7%)
Muscle spasms	2/34 (5.9%)
Musculoskeletal chest pain	3/34 (8.8%)
Musculoskeletal pain	5/34 (14.7%)
Pain in extremity	5/34 (14.7%)
Nervous system disorders
Dizziness	5/34 (14.7%)
Headache	2/34 (5.9%)
Syncope	2/34 (5.9%)
Psychiatric disorders
Anxiety	3/34 (8.8%)
Depression	3/34 (8.8%)
Mental status changes	2/34 (5.9%)
Respiratory, thoracic and mediastinal disorders
Cough	18/34 (52.9%)
Dyspnoea	7/34 (20.6%)
Dyspnoea exertional	5/34 (14.7%)
Epistaxis	2/34 (5.9%)
Hypoxia	4/34 (11.8%)
Idiopathic pulmonary fibrosis	3/34 (8.8%)
Nasal congestion	3/34 (8.8%)
Oropharyngeal pain	6/34 (17.6%)
Pneumothorax	2/34 (5.9%)
Productive cough	4/34 (11.8%)
Pulmonary mass	2/34 (5.9%)
Rhinitis allergic	2/34 (5.9%)
Rhinorrhoea	2/34 (5.9%)
Sinus congestion	3/34 (8.8%)
Upper-airway cough syndrome	3/34 (8.8%)
Skin and subcutaneous tissue disorders
Precancerous skin lesion	2/34 (5.9%)
Pruritus	2/34 (5.9%)
Rash	5/34 (14.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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