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

Idiopathic Pulmonary Fibrosis (IPF) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01371305
• Other study ID #: 203PF201
• Secondary ID: STX-003
• Status: Completed
• Phase: Phase 2
• Start date: July 16, 2012
• Est. completion date: March 31, 2017

Study information

• Verified date: February 2020
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: March 31, 2017
• Est. primary completion date: March 31, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 84 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fibrosis
• Idiopathic Pulmonary Fibrosis
• Idiopathic Pulmonary Fibrosis (IPF)
• Pulmonary Fibrosis

Intervention

Drug:
• BG00011
BG00011 will be administered at varying doses via subcutaneous (SC) injection
• Placebo
Sterile normal saline (0.9% Sodium Chloride for Injection) via Subcutaneous (SC) injections.

Locations

Country	Name	City	State
United States	Research Site	Atlanta	Georgia
United States	Research Site	Boston	Massachusetts
United States	Research Site	Boston	Massachusetts
United States	Research Site	Cleveland	Ohio
United States	Research Site	Houston	Texas
United States	Research Site	Kansas City	Kansas
United States	Research Site	Lebanon	New Hampshire
United States	Research Site	Nashville	Tennessee
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	up to Week 19
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Apparent Terminal Rate Constant [?z]		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
Secondary	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
Secondary	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
Secondary	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
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.	Baseline, Day 8 (Follow up)
Secondary	Number of Participants With Treatment Emergent Antibodies to BG00011		Up to Week 19