Idiopathic Pulmonary Fibrosis (IPF)
Conditions
Brief summary
The primary objective of this study is to evaluate the safety and tolerability of subcutaneously (SC) administered multiple, escalating doses of BG00011 (a humanized monoclonal antibody directed against the alpha v beta 6 (αvβ6) integrin, formerly known as STX-100) in participants with IPF. The Secondary objectives are to estimate the pharmacokinetic (PK) parameters after the 1st dose and after the last dose of multiple, escalating doses of BG00011 in participants with IPF, to assess the immunogenicity of BG00011 in participants with IPF, and to assess the effect of BG00011 on biomarkers isolated from bronchoalveolar lavage (BAL) and peripheral blood in participants with IPF.
Detailed description
This study was previously posted by Stromedix, Inc. In April, 2014, sponsorship of the trial was transferred to Biogen. The study drug name was changed from STX-100 to BG00011 and the study number was changed from STX-003 to 203PF201, to align with sponsor conventions.
Interventions
DRUGBG00011
BG00011 will be administered at varying doses via subcutaneous (SC) injection
DRUGPlacebo
Sterile normal saline (0.9% Sodium Chloride for Injection) via Subcutaneous (SC) injections.
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 84 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Clinical features consistent with IPF prior to screening (based on the American Thoracic Society (ATS)/European Respiratory Society (ERS)/Japanese Respiratory Society (JRS)/Latin American Thoracic Association (ALAT) consensus criteria for the diagnosis of IPF). 2. Forced (expiratory) Vital Capacity (FVC) ≥ 50% of predicted value. 3. DLco (corrected for hemoglobin) ≥ 30% predicted value. 4. Oxygen saturation \> 90% at rest by pulse oximetry while breathing ambient air or receiving ≤2 L/minute of supplemental oxygen. 5. Residual volume ≤ 120% predicted value. 6. Ratio of Forced Expiratory Volume over 1 second (FEV1) to FVC ≥ 0.65 after the use of a bronchodilator. 7. Other known causes of interstitial lung disease have been excluded (e.g., drug toxicities, environmental exposures, connective tissue diseases). 8. High Resolution Computed Tomography (HRCT) image fulfills the criteria for 'Usual Interstitial Pneumonia (UIP) pattern'. 9. If the HRCT image does not fulfill the criteria for 'UIP pattern' a surgical lung biopsy is necessary for the diagnosis of IPF (lung biopsy performed prior to screening is acceptable). If a lung biopsy has been performed, it must fulfill the histopathological criteria for either 'UIP pattern' or 'probable UIP pattern' with the appropriate HRCT correlate. 10. Adequate bone marrow and liver function. 11. Patient has a life expectancy of at least 12 months. Key
Exclusion criteria
1. Findings that are diagnostic of a condition other than UIP on surgical lung biopsy (performed either before or after screening), HRCT imaging, transbronchial lung biopsy, or bronchoalveolar lavage (BAL). 2. Serious local infection or systemic infection within 3 months prior to screening. 3. Treatment with another investigational drug, investigational device, or approved therapy for investigational use within 4 weeks of initial screening. 4. Currently receiving high dose corticosteroid, cytotoxic therapy (e.g., chlorambucil, azathioprine, cyclophosphamide, methotrexate), nintedanib (Ofev®), vasodilator therapy for pulmonary hypertension (e.g., bosentan), unapproved and/or investigational therapy for IPF or administration of such therapeutics within 5 half-lives of the agent prior to initial screening in this study. 5. End-stage fibrotic disease requiring organ transplantation within 6 months NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | up to Week 19 | An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Serum Concentration (Cmax) of BG00011 | Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50 | — |
| Area Under the Serum Concentration Time Curve From Time 0 to Last Quantifiable Observed Concentration AUC(0-t) of BG00011 | Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50 | — |
| Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours AUC(0-168) of BG00011 | Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50 | — |
| Apparent Terminal Elimination Half Life (T1/2) of BG00011 | Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50 | — |
| Apparent Terminal Rate Constant [λz] | Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50 | — |
| Time to Reach Maximum Observed Serum Concentration (Tmax) of BG00011 | Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50 | — |
| Apparent Clearance (CL/F) of BG00011 | Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50 | — |
| Apparent Volume of Distribution (Vd/F) of BG00011 | Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50 | — |
| Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | Baseline, Day 8 (Follow up) | The expression level of 7 genes; Arachidonate 5-lipoxygenase (ALOX5), fibronectin 1 (FN1), Oxidized low density lipoprotein receptor 1 (OLR1), Plasminogen activator inhibitor-1 (PAI-1; aka SERPINE 1), Transglutaminase 2 (TGM2), Triggering receptor expressed on myeloid cells 1 (TREM1), and v-ets erythroblastosis virus E26 oncogene homolog 1 (ETS1) were assessed via BAL as well as a ratio of pSMAD2 to tSMAD2 levels. |
| Number of Participants With Treatment Emergent Antibodies to BG00011 | Up to Week 19 | — |
| Area Under the Concentration Versus Time Curve From Time Zero to Infinity AUC(0-inf) of BG00011 | Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50 | — |
Countries
United States
Participant flow
Recruitment details
The participants were enrolled across 10 sites in the US.
Pre-assignment details
Forty-one participants were randomized and received at least one dose in the study.
Participants by arm
| Arm | Count |
|---|---|
| BG00011 0.015 mg Participants with idiopathic pulmonary fibrosis (IPF) received subcutaneous (SC) injection of 0.015 milligram per kilogram (mg/kg) BG00011 once weekly for 8 doses. | 6 |
| BG00011 0.1 mg Participants with IPF received SC injection of 0.1 mg/kg BG00011 once weekly for 8 doses. | 6 |
| BG00011 0.3 mg Participants with IPF received SC injection of 0.3 mg/kg BG00011 once weekly for 8 doses. | 6 |
| BG00011 1.0 mg Participants with IPF received SC injection of 1.0 mg/kg BG00011 once weekly for 8 doses. | 7 |
| BG00011 3.0 mg Participants with IPF received SC injection of 3.0 mg/kg BG00011 once weekly for 8 doses. | 6 |
| Matching Placebo Participants with IPF received SC injection of BG00011 matching placebo once weekly for 8 doses. | 10 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 2 | 1 | 0 |
| Overall Study | Study terminated by sponsor | 0 | 0 | 0 | 0 | 3 | 1 |
| Overall Study | Subject request | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | BG00011 3.0 mg | Matching Placebo | Total | BG00011 0.015 mg | BG00011 0.1 mg | BG00011 0.3 mg | BG00011 1.0 mg |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 72 years STANDARD_DEVIATION 9.7 | 72 years STANDARD_DEVIATION 7.4 | 69 years STANDARD_DEVIATION 7.1 | 68 years STANDARD_DEVIATION 2.7 | 68 years STANDARD_DEVIATION 5.9 | 65 years STANDARD_DEVIATION 9.6 | 70 years STANDARD_DEVIATION 4 |
| Race/Ethnicity, Customized Not Hispanic or Latino | 6 Participants | 10 Participants | 41 Participants | 6 Participants | 6 Participants | 6 Participants | 7 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 10 Participants | 41 Participants | 6 Participants | 6 Participants | 6 Participants | 7 Participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 6 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 9 Participants | 35 Participants | 4 Participants | 6 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 1 / 7 | 0 / 6 | 0 / 10 |
| other Total, other adverse events | 6 / 6 | 5 / 6 | 6 / 6 | 4 / 7 | 6 / 6 | 10 / 10 |
| serious Total, serious adverse events | 1 / 6 | 0 / 6 | 0 / 6 | 2 / 7 | 1 / 6 | 0 / 10 |
Outcome results
Primary
Number of Participants With Adverse Events (AEs)
An AE was any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment.
Time frame: up to Week 19
Population: The Safety population consisted of all participants who received at least one dose of BG00011 or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BG00011 0.015 mg | Number of Participants With Adverse Events (AEs) | 6 Participants |
| BG00011 0.1 mg | Number of Participants With Adverse Events (AEs) | 5 Participants |
| BG00011 0.3 mg | Number of Participants With Adverse Events (AEs) | 6 Participants |
| BG00011 1.0 mg | Number of Participants With Adverse Events (AEs) | 4 Participants |
| BG00011 3.0 mg | Number of Participants With Adverse Events (AEs) | 6 Participants |
| Matching Placebo | Number of Participants With Adverse Events (AEs) | 7 Participants |
Secondary
Apparent Clearance (CL/F) of BG00011
Time frame: Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50
Population: PK population = Safety population. Data for this outcome measure was not collected at Day 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BG00011 0.015 mg | Apparent Clearance (CL/F) of BG00011 | Day 50 | 0.913 milliliter/hour/kilogram (mL/hr/kg) | — |
| BG00011 0.1 mg | Apparent Clearance (CL/F) of BG00011 | Day 50 | 0.758 milliliter/hour/kilogram (mL/hr/kg) | Standard Deviation 0.29 |
| BG00011 0.3 mg | Apparent Clearance (CL/F) of BG00011 | Day 50 | 0.801 milliliter/hour/kilogram (mL/hr/kg) | Standard Deviation 0.441 |
| BG00011 1.0 mg | Apparent Clearance (CL/F) of BG00011 | Day 50 | 0.501 milliliter/hour/kilogram (mL/hr/kg) | Standard Deviation 0.172 |
| BG00011 3.0 mg | Apparent Clearance (CL/F) of BG00011 | Day 50 | 0.486 milliliter/hour/kilogram (mL/hr/kg) | — |
| Unknown | Apparent Clearance (CL/F) of BG00011 | Day 1 | — milliliter/hour/kilogram (mL/hr/kg) | — |
Secondary
Apparent Terminal Elimination Half Life (T1/2) of BG00011
Time frame: Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50
Population: PK population = Safety population. Data for this outcome measure was not collected at Day 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BG00011 0.015 mg | Apparent Terminal Elimination Half Life (T1/2) of BG00011 | Day 50 | 178 hour | — |
| BG00011 0.1 mg | Apparent Terminal Elimination Half Life (T1/2) of BG00011 | Day 50 | 177 hour | Standard Deviation 123 |
| BG00011 0.3 mg | Apparent Terminal Elimination Half Life (T1/2) of BG00011 | Day 50 | 168 hour | Standard Deviation 56.8 |
| BG00011 1.0 mg | Apparent Terminal Elimination Half Life (T1/2) of BG00011 | Day 50 | 178 hour | Standard Deviation 60.9 |
| BG00011 3.0 mg | Apparent Terminal Elimination Half Life (T1/2) of BG00011 | Day 50 | 250 hour | — |
| Unknown | Apparent Terminal Elimination Half Life (T1/2) of BG00011 | Day 1 | — hour | — |
Secondary
Apparent Terminal Rate Constant [λz]
Time frame: Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50
Population: PK population = Safety population. Data for this outcome measure was not collected at Day 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BG00011 0.015 mg | Apparent Terminal Rate Constant [λz] | Day 50 | 0.00390 hour | — |
| BG00011 0.1 mg | Apparent Terminal Rate Constant [λz] | Day 50 | 0.00508 hour | Standard Deviation 0.00226 |
| BG00011 0.3 mg | Apparent Terminal Rate Constant [λz] | Day 50 | 0.00442 hour | Standard Deviation 0.00112 |
| BG00011 1.0 mg | Apparent Terminal Rate Constant [λz] | Day 50 | 0.00423 hour | Standard Deviation 0.00123 |
| BG00011 3.0 mg | Apparent Terminal Rate Constant [λz] | Day 50 | 0.00286 hour | — |
| Unknown | Apparent Terminal Rate Constant [λz] | Day 1 | — hour | — |
Secondary
Apparent Volume of Distribution (Vd/F) of BG00011
Time frame: Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50
Population: PK population = safety population. Data for this outcome measure was not analysed on day 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BG00011 0.015 mg | Apparent Volume of Distribution (Vd/F) of BG00011 | Day 50 | 234 milliliter per kilogram (mL/kg) | — |
| BG00011 0.1 mg | Apparent Volume of Distribution (Vd/F) of BG00011 | Day 50 | 183 milliliter per kilogram (mL/kg) | Standard Deviation 96 |
| BG00011 0.3 mg | Apparent Volume of Distribution (Vd/F) of BG00011 | Day 50 | 183 milliliter per kilogram (mL/kg) | Standard Deviation 88 |
| BG00011 1.0 mg | Apparent Volume of Distribution (Vd/F) of BG00011 | Day 50 | 120 milliliter per kilogram (mL/kg) | Standard Deviation 29.8 |
| BG00011 3.0 mg | Apparent Volume of Distribution (Vd/F) of BG00011 | Day 50 | 168 milliliter per kilogram (mL/kg) | — |
| Unknown | Apparent Volume of Distribution (Vd/F) of BG00011 | Day 1 | — milliliter per kilogram (mL/kg) | — |
Secondary
Area Under the Concentration Versus Time Curve From Time Zero to Infinity AUC(0-inf) of BG00011
Time frame: Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50
Population: PK population = Safety population. Data for this outcome measure was not collected at Day 1.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BG00011 0.015 mg | Area Under the Concentration Versus Time Curve From Time Zero to Infinity AUC(0-inf) of BG00011 | Day 50 | 41900 hr*ng/mL | — |
| BG00011 0.1 mg | Area Under the Concentration Versus Time Curve From Time Zero to Infinity AUC(0-inf) of BG00011 | Day 50 | 362000 hr*ng/mL | Standard Deviation 173000 |
| BG00011 0.3 mg | Area Under the Concentration Versus Time Curve From Time Zero to Infinity AUC(0-inf) of BG00011 | Day 50 | 1190000 hr*ng/mL | Standard Deviation 690000 |
| BG00011 1.0 mg | Area Under the Concentration Versus Time Curve From Time Zero to Infinity AUC(0-inf) of BG00011 | Day 50 | 7250000 hr*ng/mL | Standard Deviation 4230000 |
| BG00011 3.0 mg | Area Under the Concentration Versus Time Curve From Time Zero to Infinity AUC(0-inf) of BG00011 | Day 50 | 24300000 hr*ng/mL | — |
| Unknown | Area Under the Concentration Versus Time Curve From Time Zero to Infinity AUC(0-inf) of BG00011 | Day 1 | — hr*ng/mL | — |
Secondary
Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours AUC(0-168) of BG00011
Time frame: Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50
Population: PK population = Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BG00011 0.015 mg | Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours AUC(0-168) of BG00011 | Day 1 | 9200 hr*ng/mL | — |
| BG00011 0.015 mg | Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours AUC(0-168) of BG00011 | Day 50 | 21000 hr*ng/mL | Standard Deviation 8250 |
| BG00011 0.1 mg | Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours AUC(0-168) of BG00011 | Day 1 | 44800 hr*ng/mL | Standard Deviation 24800 |
| BG00011 0.1 mg | Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours AUC(0-168) of BG00011 | Day 50 | 159000 hr*ng/mL | Standard Deviation 91200 |
| BG00011 0.3 mg | Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours AUC(0-168) of BG00011 | Day 1 | 92600 hr*ng/mL | Standard Deviation 40500 |
| BG00011 0.3 mg | Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours AUC(0-168) of BG00011 | Day 50 | 465000 hr*ng/mL | Standard Deviation 209000 |
| BG00011 1.0 mg | Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours AUC(0-168) of BG00011 | Day 50 | 2290000 hr*ng/mL | Standard Deviation 769000 |
| BG00011 1.0 mg | Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours AUC(0-168) of BG00011 | Day 1 | 497000 hr*ng/mL | Standard Deviation 242000 |
| BG00011 3.0 mg | Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours AUC(0-168) of BG00011 | Day 1 | 1690000 hr*ng/mL | Standard Deviation 438000 |
| BG00011 3.0 mg | Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours AUC(0-168) of BG00011 | Day 50 | 8310000 hr*ng/mL | Standard Deviation 2840000 |
Secondary
Area Under the Serum Concentration Time Curve From Time 0 to Last Quantifiable Observed Concentration AUC(0-t) of BG00011
Time frame: Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50
Population: PK population = Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BG00011 0.015 mg | Area Under the Serum Concentration Time Curve From Time 0 to Last Quantifiable Observed Concentration AUC(0-t) of BG00011 | Day 1 | 9200 hours nanogram per milliliter (hr*ng/mL) | — |
| BG00011 0.015 mg | Area Under the Serum Concentration Time Curve From Time 0 to Last Quantifiable Observed Concentration AUC(0-t) of BG00011 | Day 50 | 44600 hours nanogram per milliliter (hr*ng/mL) | Standard Deviation 39400 |
| BG00011 0.1 mg | Area Under the Serum Concentration Time Curve From Time 0 to Last Quantifiable Observed Concentration AUC(0-t) of BG00011 | Day 1 | 44800 hours nanogram per milliliter (hr*ng/mL) | Standard Deviation 24800 |
| BG00011 0.1 mg | Area Under the Serum Concentration Time Curve From Time 0 to Last Quantifiable Observed Concentration AUC(0-t) of BG00011 | Day 50 | 344000 hours nanogram per milliliter (hr*ng/mL) | Standard Deviation 169000 |
| BG00011 0.3 mg | Area Under the Serum Concentration Time Curve From Time 0 to Last Quantifiable Observed Concentration AUC(0-t) of BG00011 | Day 1 | 92600 hours nanogram per milliliter (hr*ng/mL) | Standard Deviation 40500 |
| BG00011 0.3 mg | Area Under the Serum Concentration Time Curve From Time 0 to Last Quantifiable Observed Concentration AUC(0-t) of BG00011 | Day 50 | 1080000 hours nanogram per milliliter (hr*ng/mL) | Standard Deviation 554000 |
| BG00011 1.0 mg | Area Under the Serum Concentration Time Curve From Time 0 to Last Quantifiable Observed Concentration AUC(0-t) of BG00011 | Day 50 | 6370000 hours nanogram per milliliter (hr*ng/mL) | Standard Deviation 3980000 |
| BG00011 1.0 mg | Area Under the Serum Concentration Time Curve From Time 0 to Last Quantifiable Observed Concentration AUC(0-t) of BG00011 | Day 1 | 513000 hours nanogram per milliliter (hr*ng/mL) | Standard Deviation 264000 |
| BG00011 3.0 mg | Area Under the Serum Concentration Time Curve From Time 0 to Last Quantifiable Observed Concentration AUC(0-t) of BG00011 | Day 1 | 1730000 hours nanogram per milliliter (hr*ng/mL) | Standard Deviation 525000 |
| BG00011 3.0 mg | Area Under the Serum Concentration Time Curve From Time 0 to Last Quantifiable Observed Concentration AUC(0-t) of BG00011 | Day 50 | 25700000 hours nanogram per milliliter (hr*ng/mL) | Standard Deviation 17700000 |
Secondary
Maximum Observed Serum Concentration (Cmax) of BG00011
Time frame: Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50
Population: PK population = Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BG00011 0.015 mg | Maximum Observed Serum Concentration (Cmax) of BG00011 | Day 1 | 71.3 nanogram per milliliter (ng/mL) | — |
| BG00011 0.015 mg | Maximum Observed Serum Concentration (Cmax) of BG00011 | Day 50 | 134 nanogram per milliliter (ng/mL) | Standard Deviation 44.6 |
| BG00011 0.1 mg | Maximum Observed Serum Concentration (Cmax) of BG00011 | Day 1 | 335 nanogram per milliliter (ng/mL) | Standard Deviation 178 |
| BG00011 0.1 mg | Maximum Observed Serum Concentration (Cmax) of BG00011 | Day 50 | 1080 nanogram per milliliter (ng/mL) | Standard Deviation 676 |
| BG00011 0.3 mg | Maximum Observed Serum Concentration (Cmax) of BG00011 | Day 1 | 716 nanogram per milliliter (ng/mL) | Standard Deviation 281 |
| BG00011 0.3 mg | Maximum Observed Serum Concentration (Cmax) of BG00011 | Day 50 | 3170 nanogram per milliliter (ng/mL) | Standard Deviation 1380 |
| BG00011 1.0 mg | Maximum Observed Serum Concentration (Cmax) of BG00011 | Day 50 | 15400 nanogram per milliliter (ng/mL) | Standard Deviation 5180 |
| BG00011 1.0 mg | Maximum Observed Serum Concentration (Cmax) of BG00011 | Day 1 | 4370 nanogram per milliliter (ng/mL) | Standard Deviation 1350 |
| BG00011 3.0 mg | Maximum Observed Serum Concentration (Cmax) of BG00011 | Day 1 | 12900 nanogram per milliliter (ng/mL) | Standard Deviation 3130 |
| BG00011 3.0 mg | Maximum Observed Serum Concentration (Cmax) of BG00011 | Day 50 | 52800 nanogram per milliliter (ng/mL) | Standard Deviation 17600 |
Secondary
Number of Participants With Treatment Emergent Antibodies to BG00011
Time frame: Up to Week 19
Population: The Safety population consisted of all participants who received at least one dose of BG00011 or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BG00011 0.015 mg | Number of Participants With Treatment Emergent Antibodies to BG00011 | 1 participants |
| BG00011 0.1 mg | Number of Participants With Treatment Emergent Antibodies to BG00011 | 0 participants |
| BG00011 0.3 mg | Number of Participants With Treatment Emergent Antibodies to BG00011 | 0 participants |
| BG00011 1.0 mg | Number of Participants With Treatment Emergent Antibodies to BG00011 | 0 participants |
| BG00011 3.0 mg | Number of Participants With Treatment Emergent Antibodies to BG00011 | 0 participants |
| Matching Placebo | Number of Participants With Treatment Emergent Antibodies to BG00011 | 0 participants |
Secondary
Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL)
The expression level of 7 genes; Arachidonate 5-lipoxygenase (ALOX5), fibronectin 1 (FN1), Oxidized low density lipoprotein receptor 1 (OLR1), Plasminogen activator inhibitor-1 (PAI-1; aka SERPINE 1), Transglutaminase 2 (TGM2), Triggering receptor expressed on myeloid cells 1 (TREM1), and v-ets erythroblastosis virus E26 oncogene homolog 1 (ETS1) were assessed via BAL as well as a ratio of pSMAD2 to tSMAD2 levels.
Time frame: Baseline, Day 8 (Follow up)
Population: The Pharmacodynamic population consisted of all participants who received at least 1 multiple dose injection of BG00011 and have a corresponding sample collected for BAL and/or blood biomarkers.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BG00011 0.015 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | OLR1; PC at Day 8 (Follow Up) | -4.79 Percentage | Standard Deviation 31.104 |
| BG00011 0.015 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | FN1; PC at Day 8 (Follow Up) | 0.42 Percentage | Standard Deviation 20.776 |
| BG00011 0.015 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | ALOX5; PC at Day 8 (Follow Up) | 4.39 Percentage | Standard Deviation 16.56 |
| BG00011 0.015 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | PAI-1; aka SERPINE 1; PC at Day 8 (Follow Up) | 26.98 Percentage | Standard Deviation 55.559 |
| BG00011 0.015 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | TGM2; PC at Day 8 (Follow Up) | 0.71 Percentage | Standard Deviation 31.009 |
| BG00011 0.015 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | TREM1; PC at Day 8 (Follow Up) | -3.71 Percentage | Standard Deviation 20.135 |
| BG00011 0.015 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | ETS1; PC at Day 8 (Follow Up) | 3.16 Percentage | Standard Deviation 53.425 |
| BG00011 0.015 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | pSMAD2 to tSMAD2; PC at Day 8 (Follow Up) | 23.91 Percentage | Standard Deviation 54.293 |
| BG00011 0.1 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | PAI-1; aka SERPINE 1; PC at Day 8 (Follow Up) | -28.27 Percentage | Standard Deviation 10.055 |
| BG00011 0.1 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | pSMAD2 to tSMAD2; PC at Day 8 (Follow Up) | -3.33 Percentage | Standard Deviation 29.724 |
| BG00011 0.1 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | ALOX5; PC at Day 8 (Follow Up) | -0.25 Percentage | Standard Deviation 11.154 |
| BG00011 0.1 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | ETS1; PC at Day 8 (Follow Up) | -11.52 Percentage | Standard Deviation 26.342 |
| BG00011 0.1 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | TREM1; PC at Day 8 (Follow Up) | -2.01 Percentage | Standard Deviation 16.654 |
| BG00011 0.1 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | OLR1; PC at Day 8 (Follow Up) | -1.58 Percentage | Standard Deviation 16.207 |
| BG00011 0.1 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | FN1; PC at Day 8 (Follow Up) | -4.83 Percentage | Standard Deviation 22.035 |
| BG00011 0.1 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | TGM2; PC at Day 8 (Follow Up) | -3.06 Percentage | Standard Deviation 41.757 |
| BG00011 0.3 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | FN1; PC at Day 8 (Follow Up) | -16.84 Percentage | Standard Deviation 15.424 |
| BG00011 0.3 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | OLR1; PC at Day 8 (Follow Up) | -15.09 Percentage | Standard Deviation 25.235 |
| BG00011 0.3 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | PAI-1; aka SERPINE 1; PC at Day 8 (Follow Up) | 7.83 Percentage | Standard Deviation 30.064 |
| BG00011 0.3 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | pSMAD2 to tSMAD2; PC at Day 8 (Follow Up) | -39.82 Percentage | Standard Deviation 24.675 |
| BG00011 0.3 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | TGM2; PC at Day 8 (Follow Up) | -13.17 Percentage | Standard Deviation 35.547 |
| BG00011 0.3 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | TREM1; PC at Day 8 (Follow Up) | -7.66 Percentage | Standard Deviation 21.151 |
| BG00011 0.3 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | ETS1; PC at Day 8 (Follow Up) | -10.54 Percentage | Standard Deviation 43.866 |
| BG00011 0.3 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | ALOX5; PC at Day 8 (Follow Up) | -5.16 Percentage | Standard Deviation 23.074 |
| BG00011 1.0 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | ETS1; PC at Day 8 (Follow Up) | 240.59 Percentage | Standard Deviation 245.766 |
| BG00011 1.0 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | TREM1; PC at Day 8 (Follow Up) | -48.33 Percentage | Standard Deviation 23.511 |
| BG00011 1.0 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | TGM2; PC at Day 8 (Follow Up) | -53.15 Percentage | Standard Deviation 28.412 |
| BG00011 1.0 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | ALOX5; PC at Day 8 (Follow Up) | -51.07 Percentage | Standard Deviation 22.942 |
| BG00011 1.0 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | OLR1; PC at Day 8 (Follow Up) | -63.64 Percentage | Standard Deviation 18.657 |
| BG00011 1.0 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | PAI-1; aka SERPINE 1; PC at Day 8 (Follow Up) | -26.06 Percentage | Standard Deviation 38.247 |
| BG00011 1.0 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | pSMAD2 to tSMAD2; PC at Day 8 (Follow Up) | -63.74 Percentage | Standard Deviation 34.674 |
| BG00011 1.0 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | FN1; PC at Day 8 (Follow Up) | -65.41 Percentage | Standard Deviation 16.174 |
| BG00011 3.0 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | pSMAD2 to tSMAD2; PC at Day 8 (Follow Up) | -76.20 Percentage | Standard Deviation 14.834 |
| BG00011 3.0 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | ALOX5; PC at Day 8 (Follow Up) | -70.90 Percentage | Standard Deviation 14.633 |
| BG00011 3.0 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | TGM2; PC at Day 8 (Follow Up) | -71.35 Percentage | Standard Deviation 17.449 |
| BG00011 3.0 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | TREM1; PC at Day 8 (Follow Up) | -63.13 Percentage | Standard Deviation 13.7 |
| BG00011 3.0 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | ETS1; PC at Day 8 (Follow Up) | 103.16 Percentage | Standard Deviation 152.301 |
| BG00011 3.0 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | FN1; PC at Day 8 (Follow Up) | -77.42 Percentage | Standard Deviation 17.989 |
| BG00011 3.0 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | OLR1; PC at Day 8 (Follow Up) | -77.97 Percentage | Standard Deviation 14.602 |
| BG00011 3.0 mg | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | PAI-1; aka SERPINE 1; PC at Day 8 (Follow Up) | 71.44 Percentage | Standard Deviation 115.042 |
| Matching Placebo | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | pSMAD2 to tSMAD2; PC at Day 8 (Follow Up) | 28.59 Percentage | Standard Deviation 52.27 |
| Matching Placebo | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | TGM2; PC at Day 8 (Follow Up) | 15.06 Percentage | Standard Deviation 59.874 |
| Matching Placebo | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | OLR1; PC at Day 8 (Follow Up) | -3.56 Percentage | Standard Deviation 21.215 |
| Matching Placebo | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | PAI-1; aka SERPINE 1; PC at Day 8 (Follow Up) | -1.40 Percentage | Standard Deviation 59.537 |
| Matching Placebo | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | TREM1; PC at Day 8 (Follow Up) | -12.83 Percentage | Standard Deviation 17.397 |
| Matching Placebo | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | FN1; PC at Day 8 (Follow Up) | -8.27 Percentage | Standard Deviation 23.881 |
| Matching Placebo | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | ETS1; PC at Day 8 (Follow Up) | 65.10 Percentage | Standard Deviation 146.69 |
| Matching Placebo | Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL) | ALOX5; PC at Day 8 (Follow Up) | -7.87 Percentage | Standard Deviation 15.793 |
Secondary
Time to Reach Maximum Observed Serum Concentration (Tmax) of BG00011
Time frame: Pre-dose, 8, 24, 48 and 96 hours post-dose on Day 1; pre-dose on Days 8, 15, 22, 29, 36, 43; pre-dose, 24, 48, 96, 168, 336, 504, 672, 1344, 2016 hours post-dose on Day 50
Population: Pharmacokinetic (PK) population = Safety population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BG00011 0.015 mg | Time to Reach Maximum Observed Serum Concentration (Tmax) of BG00011 | Day 1 | 168 hours | — |
| BG00011 0.015 mg | Time to Reach Maximum Observed Serum Concentration (Tmax) of BG00011 | Day 50 | 42.7 hours | Standard Deviation 61.9 |
| BG00011 0.1 mg | Time to Reach Maximum Observed Serum Concentration (Tmax) of BG00011 | Day 1 | 101 hours | Standard Deviation 42.9 |
| BG00011 0.1 mg | Time to Reach Maximum Observed Serum Concentration (Tmax) of BG00011 | Day 50 | 64.0 hours | Standard Deviation 24.8 |
| BG00011 0.3 mg | Time to Reach Maximum Observed Serum Concentration (Tmax) of BG00011 | Day 1 | 132 hours | Standard Deviation 39.4 |
| BG00011 0.3 mg | Time to Reach Maximum Observed Serum Concentration (Tmax) of BG00011 | Day 50 | 64.0 hours | Standard Deviation 51.8 |
| BG00011 1.0 mg | Time to Reach Maximum Observed Serum Concentration (Tmax) of BG00011 | Day 50 | 32.0 hours | Standard Deviation 19.6 |
| BG00011 1.0 mg | Time to Reach Maximum Observed Serum Concentration (Tmax) of BG00011 | Day 1 | 134 hours | Standard Deviation 60.5 |
| BG00011 3.0 mg | Time to Reach Maximum Observed Serum Concentration (Tmax) of BG00011 | Day 1 | 96.4 hours | Standard Deviation 53.5 |
| BG00011 3.0 mg | Time to Reach Maximum Observed Serum Concentration (Tmax) of BG00011 | Day 50 | 38.0 hours | Standard Deviation 39.4 |