STX-100 in Patients With Idiopathic Pulmonary Fibrosis (IPF)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Dose-Escalation Study of STX-100 in Patients With Idiopathic Pulmonary Fibrosis (IPF)

Conditions
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Idiopathic Pulmonary Fibrosis (IPF)

Intervention / Treatment
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* Drug: BG00011
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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). Forced (expiratory) Vital Capacity (FVC) ≥ 50% of predicted value. DLco (corrected for hemoglobin) ≥ 30% predicted value. Oxygen saturation > 90% at rest by pulse oximetry while breathing ambient air or receiving ≤2 L/minute of supplemental oxygen. Residual volume ≤ 120% predicted value. Ratio of Forced Expiratory Volume over 1 second (FEV1) to FVC ≥ 0.65 after the use of a bronchodilator. Other known causes of interstitial lung disease have been excluded (e.g., drug toxicities, environmental exposures, connective tissue diseases). High Resolution Computed Tomography (HRCT) image fulfills the criteria for 'Usual Interstitial Pneumonia (UIP) pattern'. 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. Adequate bone marrow and liver function. Patient has a life expectancy of at least 12 months. Key Exclusion Criteria: 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). Serious local infection or systemic infection within 3 months prior to screening. Treatment with another investigational drug, investigational device, or approved therapy for investigational use within 4 weeks of initial screening. 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. End-stage fibrotic disease requiring organ transplantation within 6 months NOTE: Other protocol defined Inclusion/Exclusion Criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 84 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BG00011<br>Participants will receive 8 consecutive weekly doses of BG00011 | Drug: BG00011<br>* BG00011 will be administered at varying doses via subcutaneous (SC) injection<br>* Other names: STX-100;|
| Placebo Comparator: Placebo<br>Participants will receive 8 consecutive weekly doses of placebo. | Drug: Placebo<br>* Sterile normal saline (0.9% Sodium Chloride for Injection) via Subcutaneous (SC) injections.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | up to Week 19 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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) | 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. | Baseline, Day 8 (Follow up) | 
| Number of Participants With Treatment Emergent Antibodies to BG00011 |  | Up to Week 19 |