04 February 2019 by Peter Fernandes

Actigraphy as a clinically meaningful endpoint to detect change after treatment with iNO (30 mcg/kg-IBW/hr) in patients with Pulmonary Hypertension associated with Pulmonary Fibrosis

Background:

Pulmonary fibrosis (PF) is made up of a wide variety of fibrotic lung diseases, the largest of which is IPF (Idiopathic Pulmonary Fibrosis). Pulmonary hypertension frequently complicates pulmonary fibrosis (PH-PF) and is associated with impaired functional status and reduced life expectancy. There are currently no approved therapies to treat PH-PF. Additionally, there are no established regulatory endpoints for PH-PF. Patients with PH-PF have significantly lower activity compared to healthy subjects, and have poorer health outcomes. Wearable activity monitoring (actigraphy) can provide continuous objective real-world physical activity data, which has been correlated to clinically meaningful health outcomes. Actigraphy has also been utilized as the primary end-point in pivotal trials in other cardiopulmonary indications such as heart failure and COPD.

Aim:

To determine if actigraphy can provide clinically meaningful data sensitive to functional change after treatment in a population with PH-PF. Evaluate if actigraphy could serve as a regulatory endpoint for future pivotal studies based on the safety and clinical benefit seen in the iNO-PF study.

Methods:

iNO-PF is a double-blind, placebo-controlled Phase 2b study assessing the safety and efficacy of pulsed, inhaled nitric oxide (iNO) at a dose of 30 mcg/kg-IBW/hr (iNO 30) in subjects with PH-PF. Subjects were randomized (1:1) to receive active (iNO 30) or placebo for 8 weeks of blinded treatment. A wrist-worn medical grade activity monitor was used to assess changes in daily activity at 8 weeks as compared to baseline. Additional safety and efficacy parameters were also evaluated over the course of the study.

Results:

Statistically significant improvements in multiple clinically meaningful activity parameters were observed in the treatment arm. Subjects on pulsed inhaled nitric oxide (iNO) demonstrated an increase of 8% in moderate activity versus a 26% decrease for subjects on placebo (p=0.04). Subjects on iNO showed no decline in their overall activity levels versus a 12% decline for subjects on placebo (p=0.05). iNO was well-tolerated with no safety concerns.

Conclusion:

iNO 30 provides both clinically and statistically meaningful benefit in moderate and overall activity as compared to placebo. The demonstrable difference discerned over eight weeks, coupled with the advantage of a continuous quantitative assessment provided by actigraphy supports its role as a primary endpoint in clinical trials in subjects with PH-PF

About the author


profile picture of Peter Fernandes

Peter Fernandes

VP, Chief Regulatory, Safety & Quality Officer

Bellerophon Therapeutics

United States

Key Contributors

S.D. Nathan 1, K. Flaherty 2, M. Glassberg Ceste 3, G. Raghu 4, J. Swigris 5, R. Alvarez 3, N. Ettinger 6, J. Loyd 7, P. Fernandes 8, H. Gillies 8, P. Shah 8, L. Lancaster 9 : 1. Virginia Commonwealth University and Inova Fairfax Hospital 2. University of Michigan 3. University of Miami 4. University of Washington Medical Center 5. Department of Medicine, National Jewish, Denver Colorado 6. The Lung Research Center – Missouri 7. Vanderbilt University Medical Center 8. Bellerophon Therapeutics 9. Pulmonary and Critical Care Medicine Vanderbilt University Medical Center


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