A Prospective, Randomized, Placebo-Controlled Multicenter Study to Evaluate the Performance of the IBV Valve System for the Treatment of Severe Emphysema

The Spiration IBV* Valve System is a device implanted in the lung airway
intended to treat diseased or damaged lung. The valve limits airflow to
selected areas, which improves health status.

The objective of this randomized, blinded, multicenter, controlled study is to
compare the performance of the IBV* Valve System (treatment group) to a control
group receiving a sham bronchoscopy procedure without valve placement

This is a multicenter, prospective, randomized, blinded, placebo controlled
study designed to evaluate treatment with the Spiration® IBV* Valve System
compared to treatment with no valves implanted in the control group. The
control group will be treated and tested in the same fashion as the treatment
group, except that there will be no valves placed during the bronchoscopic
procedure.
Subjects in the control group who have completed the 3-month testing and all
follow-up visits will be evaluated for any co-morbidities or contraindications
for treatment with IBV* Valve System. If none, the rollover subjects will
receive treatment with the IBV* Valve System and then be evaluated after 3
months.
In this study, 100 subjects will be enrolled at up to 15 study sites. Subjects
will be randomized in a 1:1 allocation ratio to either the IBV* Valve treatment
group or the control group.

All study subjects will be evaluated and tested at the same intervals, i.e.,
baseline, 1 month, 3 months, and 6 months. During the bronchoscopic procedure,
to be performed on study Day 0, study subjects will be randomized to either the
treatment or control group using a computer-generated randomization schema.

Subjects assigned to the treatment group will receive IBV* Valve treatment.
Subjects in the control group will receive the same procedure, anesthesia, and
a diagnostic bronchoscopy, but no valves will be placed. All subjects will be
monitored through the 3-month follow-up visit.

Subjects in the control group who have completed the 3-month testing and
follow-up visits will be evaluated for continued eligibility according to the
protocol inclusion/exclusion criteria. If still eligible, they will receive
treatment with the IBV* Valve System and be followed in accordance with the
Summary of Crossover Tests and Procedures in Appendix B.

Risk analysis was performed to assess potential hazards that might be
associated with the IBVTM Valve System. Failure Mode and Effects Analyses
(FMEA) were conducted on both the design and manufacture of the system
components including the valve, deployment catheter, and airway sizing kit. The
FMEAs cover the patient, operator, clinical environment, and the products
during shipping, intended use, and storage. The Spiration, Inc. FMEAs are
controlled documents reviewed and approved by designated functions to ensure
that appropriate considerations are made.

The results of the risk analyses show that the risk levels are acceptable when
weighed against the benefits from the IBVTM Valve System. Spiration management
considers the risks and benefits of accepting any conditions with risk levels
above the established threshold, and as they occur, management ensures action
plans to reduce the risks are effectively implemented.