Clinical trial NCT01371305: STX-100 in Patients With Idiopathic Pulmonary Fibrosis (IPF)
Official title: Randomized, Double-Blind, Placebo-Controlled, Multiple Dose, Dose-Escalation Study of STX-100 in Patients With Idiopathic Pulmonary Fibrosis (IPF)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis (IPF)
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2011-06-10
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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/Exclusion Criteria may apply.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: up to Week 19
Secondary outcomes:
measure: Time to Reach Maximum Observed Serum Concentration (Tmax) of BG00011
timeFrame: 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
measure: Maximum Observed Serum Concentration (Cmax) of BG00011
timeFrame: 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
measure: Area Under the Serum Concentration Time Curve From Time 0 to Last Quantifiable Observed Concentration AUC(0-t) of BG00011
timeFrame: 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
measure: Area Under the Serum Concentration-Time Curve From Time 0 to 168 Hours AUC(0-168) of BG00011
timeFrame: 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
measure: Apparent Terminal Elimination Half Life (T1/2) of BG00011
timeFrame: 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
measure: Apparent Terminal Rate Constant [λz]
timeFrame: 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
measure: Area Under the Concentration Versus Time Curve From Time Zero to Infinity AUC(0-inf) of BG00011
timeFrame: 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
measure: Apparent Clearance (CL/F) of BG00011
timeFrame: 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
measure: Apparent Volume of Distribution (Vd/F) of BG00011
timeFrame: 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
measure: Percentage Change (PC) From Baseline in Biomarkers Isolated From Bronchoalveolar Lavage (BAL)
timeFrame: Baseline, Day 8 (Follow up)
measure: Number of Participants With Treatment Emergent Antibodies to BG00011
timeFrame: Up to Week 19
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Research Site
state: California
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Kansas City
country: United States
facility: Research Site
state: Kansas
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Lebanon
country: United States
facility: Research Site
state: New Hampshire
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Houston
country: United States
facility: Research Site
state: Texas
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References: