Idiopathic Pulmonary Fibrosis
Conditions
Keywords
Idiopathic, Pulmonary, Fibrosis, IPF
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.
Interventions
DRUGSimtuzumab
200 mg/mL administered intravenously biweekly (per original protocol) or 125 mg/mL self-administered subcutaneously every 7 ± 2 days (per protocol amendment 1)
Sponsors
Gilead Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| All-cause Mortality | Up to 165 weeks | All-cause mortality was assessed as a number of participants who died from any cause. |
| Relative Change From Baseline in Serum Lysyl Oxidase-like 2 (sLOXL2) Levels at Weeks 72 and 120 | Weeks 72 and 120 | — |
Countries
United States
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 details
37 participants were screened.
Participants by arm
| Arm | Count |
|---|---|
| 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) | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| 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
| Characteristic | Simtuzumab |
|---|---|
| Age, Continuous | 67.9 years STANDARD_DEVIATION 7.25 |
| Forced expirator volume in the first second of expiration (FEV1)/FVC Ratio | 0.8 liter STANDARD_DEVIATION 0.23 |
| Forced vital capacity (FVC) Percent Predicted | 69.9 FVC % predicted STANDARD_DEVIATION 14.18 |
| FVC % Predicted Category Mild | 12 Participants |
| FVC % Predicted Category Moderate | 16 Participants |
| FVC % Predicted Category Severe | 6 Participants |
| Hemoglobin-Corrected Carbon dioxide diffusing capacity (DLCO) Predicted | 12.2 DLCO % predicted STANDARD_DEVIATION 4.22 |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 33 Participants |
| Race/Ethnicity, Customized White | 34 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 34 |
| other Total, other adverse events | 33 / 34 |
| serious Total, serious adverse events | 12 / 34 |
Outcome results
Primary
Overall Safety Profile of Simtuzumab
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)
Population: Safety Analysis Set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Simtuzumab | Overall Safety Profile of Simtuzumab | Serious Adverse Events | 35.3 percentage of participants |
| Simtuzumab | Overall Safety Profile of Simtuzumab | SAEs Related to simtuzumab | 5.9 percentage of participants |
| Simtuzumab | Overall Safety Profile of Simtuzumab | AEs leading to discontinuation of simtuzumab | 29.4 percentage of participants |
| Simtuzumab | Overall Safety Profile of Simtuzumab | Adverse Events (AEs) | 97.1 percentage of participants |
| Simtuzumab | Overall Safety Profile of Simtuzumab | Grade 3 or 4 AEs | 47.1 percentage of participants |
Secondary
All-cause Mortality
All-cause mortality was assessed as a number of participants who died from any cause.
Time frame: Up to 165 weeks
Population: Safety Analysis Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Simtuzumab | All-cause Mortality | 3 Participants |
Secondary
Relative Change From Baseline in DLCO % Predicted at 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.
Time frame: Weeks 72 and 144
Population: Participants in Safety Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Simtuzumab | 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 |
| Simtuzumab | 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
Relative Change From Baseline in FVC % Predicted at 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.
Time frame: Weeks 72 and 144
Population: Participants in Safety Analysis Set with available data were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Simtuzumab | 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 |
| Simtuzumab | 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
Relative Change From Baseline in Serum Lysyl Oxidase-like 2 (sLOXL2) Levels at Weeks 72 and 120
Time frame: Weeks 72 and 120
Population: Participants in the Safety Analysis set with available data were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Simtuzumab | 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 |
| Simtuzumab | 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 |