Trial Outcomes & Findings for Zephyrus II: Efficacy and Safety Study of Pamrevlumab in Participants With Idiopathic Pulmonary Fibrosis (IPF) (NCT NCT04419558)

NCT ID: NCT04419558

Last Updated: 2024-08-12

Results Overview

FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC was the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Least square (LS) mean and standard error (SE) were analyzed using mixed model repeated measures (MMRM).

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

372 participants

Primary outcome timeframe

Baseline, Week 48

Results posted on

2024-08-12

Participant Flow

The study included a Double-blind (DB) Period and an Open-label Extension (OLE) Period.

Participant milestones

Participant milestones
Measure	Pamrevlumab Participants received pamrevlumab 30 milligrams (mg)/kilogram (kg), administered by intravenous (IV) infusion, every 3 weeks, for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, continued to receive pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.	Placebo Participants received pamrevlumab-matching placebo, administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, received pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.
DB Period (48 Weeks) STARTED	184	188
DB Period (48 Weeks) Received at Least 1 Dose of Study Drug	183	188
DB Period (48 Weeks) COMPLETED	47	56
DB Period (48 Weeks) NOT COMPLETED	137	132
OLE Period (48 Weeks) STARTED	41	45
OLE Period (48 Weeks) COMPLETED	0	0
OLE Period (48 Weeks) NOT COMPLETED	41	45

Reasons for withdrawal

Reasons for withdrawal
Measure	Pamrevlumab Participants received pamrevlumab 30 milligrams (mg)/kilogram (kg), administered by intravenous (IV) infusion, every 3 weeks, for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, continued to receive pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.	Placebo Participants received pamrevlumab-matching placebo, administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, received pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.
DB Period (48 Weeks) Adverse Event	6	6
DB Period (48 Weeks) Death	14	11
DB Period (48 Weeks) Lost to Follow-up	1	3
DB Period (48 Weeks) Investigator Decision	0	1
DB Period (48 Weeks) Study terminated by sponsor	99	101
DB Period (48 Weeks) Disease Progression	1	0
DB Period (48 Weeks) Withdrawal by Subject	11	7
DB Period (48 Weeks) Lung Transplant	1	0
DB Period (48 Weeks) Participant Decision	4	3
OLE Period (48 Weeks) Adverse Event	3	1
OLE Period (48 Weeks) Death	4	6
OLE Period (48 Weeks) Study terminated by sponsor	34	37
OLE Period (48 Weeks) Withdrawal by Subject	0	1

Baseline Characteristics

'Number analyzed' = participants evaluable for this baseline measure.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pamrevlumab n=184 Participants Participants received pamrevlumab 30 mg/kg, administered by IV infusion, every 3 weeks, for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, continued to receive pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.	Placebo n=188 Participants Participants received pamrevlumab-matching placebo, administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, received pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.	Total n=372 Participants Total of all reporting groups
Age, Continuous	70.2 years STANDARD_DEVIATION 7.8 • n=184 Participants	70.1 years STANDARD_DEVIATION 8.2 • n=188 Participants	70.1 years STANDARD_DEVIATION 8.0 • n=372 Participants
Sex: Female, Male Female	45 Participants n=184 Participants	44 Participants n=188 Participants	89 Participants n=372 Participants
Sex: Female, Male Male	139 Participants n=184 Participants	144 Participants n=188 Participants	283 Participants n=372 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	52 Participants n=184 Participants	45 Participants n=188 Participants	97 Participants n=372 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	125 Participants n=184 Participants	141 Participants n=188 Participants	266 Participants n=372 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	7 Participants n=184 Participants	2 Participants n=188 Participants	9 Participants n=372 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=184 Participants	2 Participants n=188 Participants	2 Participants n=372 Participants
Race (NIH/OMB) Asian	42 Participants n=184 Participants	55 Participants n=188 Participants	97 Participants n=372 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=184 Participants	0 Participants n=188 Participants	0 Participants n=372 Participants
Race (NIH/OMB) Black or African American	2 Participants n=184 Participants	1 Participants n=188 Participants	3 Participants n=372 Participants
Race (NIH/OMB) White	111 Participants n=184 Participants	114 Participants n=188 Participants	225 Participants n=372 Participants
Race (NIH/OMB) More than one race	0 Participants n=184 Participants	0 Participants n=188 Participants	0 Participants n=372 Participants
Race (NIH/OMB) Unknown or Not Reported	29 Participants n=184 Participants	16 Participants n=188 Participants	45 Participants n=372 Participants
Forced Vital Capacity (FVC)	2.4811 liters STANDARD_DEVIATION 0.6477 • n=184 Participants • 'Number analyzed' = participants evaluable for this baseline measure.	2.5097 liters STANDARD_DEVIATION 0.6573 • n=187 Participants • 'Number analyzed' = participants evaluable for this baseline measure.	2.4955 liters STANDARD_DEVIATION 0.6518 • n=371 Participants • 'Number analyzed' = participants evaluable for this baseline measure.

PRIMARY outcome

Timeframe: Baseline, Week 48

Population: The ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Pamrevlumab n=70 Participants Participants received pamrevlumab 30 mg/kg, administered by IV infusion, every 3 weeks, for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, continued to receive pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.	Placebo n=76 Participants Participants received pamrevlumab-matching placebo, administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, received pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.
DB Period: Change From Baseline in FVC at Week 48	-0.30 liters Standard Error 0.057	-0.33 liters Standard Error 0.059

SECONDARY outcome

Timeframe: Up to Week 48

Population: The ITT population included all randomized participants.

Time to disease progression was defined as time from randomization to either the first occurrence of an absolute FVC percent predicted (FVCpp) decline of ≥10% from baseline or death, whichever occurred first. 'Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. For an endpoint in which less than half of the participants have encountered the events, the 'Median Time to Event' might be longer than the reported timeframe of 48 weeks.

Outcome measures

Outcome measures
Measure	Pamrevlumab n=184 Participants Participants received pamrevlumab 30 mg/kg, administered by IV infusion, every 3 weeks, for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, continued to receive pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.	Placebo n=188 Participants Participants received pamrevlumab-matching placebo, administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, received pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.
DB Period: Time to Disease Progression	59.0 weeks Due to smaller number of participants with an event, lower and upper limit of 95% confidence interval (CI) could not be calculated.	NA weeks Interval 49.4 to Due to smaller number of participants with an event, median and upper limit of 95% CI could not be calculated.

SECONDARY outcome

Timeframe: Baseline, Week 48

Population: The ITT population included all randomized participants. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.

The QLF volume is calculated as QLF=total lung capacity volume (TLC) \* % of quantitative lung fibrosis for fibrosis of the whole lung. LS mean and SE were analyzed using MMRM.

Outcome measures

Outcome measures
Measure	Pamrevlumab n=71 Participants Participants received pamrevlumab 30 mg/kg, administered by IV infusion, every 3 weeks, for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, continued to receive pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.	Placebo n=76 Participants Participants received pamrevlumab-matching placebo, administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, received pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.
DB Period: Change From Baseline in Quantitative Lung Fibrosis (QLF) Volume at Week 48	255.14 milliliters Standard Error 72.028	269.15 milliliters Standard Error 60.898

SECONDARY outcome

Timeframe: Up to Week 48

Population: The ITT population included all randomized participants.

The components of the clinical composite endpoints included acute idiopathic pulmonary fibrosis (IPF) exacerbation, respiratory hospitalization, or death. 'Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. For an endpoint in which less than half of the participants have encountered the events, the 'Median Time to Event' might be longer than the reported timeframe of 48 weeks.

Outcome measures

Outcome measures
Measure	Pamrevlumab n=184 Participants Participants received pamrevlumab 30 mg/kg, administered by IV infusion, every 3 weeks, for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, continued to receive pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.	Placebo n=188 Participants Participants received pamrevlumab-matching placebo, administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, received pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.
DB Period: Time to First Occurrence of Any Component of the Clinical Composite Endpoint, Whichever Occurred First	NA weeks Interval 59.0 to Due to smaller number of participants with an event, median and upper limit of 95% CI could not be calculated.	NA weeks Due to smaller number of participants with an event, median and 95% CI could not be calculated.

SECONDARY outcome

Timeframe: Up to Week 48

Population: The ITT population included all randomized participants.

'Median Time to Event' is an estimated value, which was calculated based on Kaplan-Meier method. For an endpoint in which less than half of the participants have encountered the events, the 'Median Time to Event' might be longer than the reported timeframe of 48 weeks.

Outcome measures

Outcome measures
Measure	Pamrevlumab n=184 Participants Participants received pamrevlumab 30 mg/kg, administered by IV infusion, every 3 weeks, for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, continued to receive pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.	Placebo n=188 Participants Participants received pamrevlumab-matching placebo, administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, received pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.
DB Period: Time to First Acute IPF Exacerbation	NA weeks Due to smaller number of participants with an event, data could not be calculated.	NA weeks Due to smaller number of participants with an event, data could not be calculated.

SECONDARY outcome

Timeframe: Up to Week 48

Population: The ITT population included all randomized participants.

Outcome measures

Outcome measures
Measure	Pamrevlumab n=184 Participants Participants received pamrevlumab 30 mg/kg, administered by IV infusion, every 3 weeks, for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, continued to receive pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.	Placebo n=188 Participants Participants received pamrevlumab-matching placebo, administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, received pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.
DB Period: Time to All-Cause Mortality	NA weeks Interval 59.0 to Due to smaller number of participants with an event, median and upper limit of 95% CI could not be calculated.	62.9 weeks Due to smaller number of participants with an event, lower and upper limit of 95% CI could not be calculated.

SECONDARY outcome

Timeframe: Up to Week 48

Population: The ITT population included all randomized participants.

Outcome measures

Outcome measures
Measure	Pamrevlumab n=184 Participants Participants received pamrevlumab 30 mg/kg, administered by IV infusion, every 3 weeks, for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, continued to receive pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.	Placebo n=188 Participants Participants received pamrevlumab-matching placebo, administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks in the DB period. Participants who completed the treatment in DB period and entered in the OLE period, received pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.
DB Period: Time to First Respiratory Hospitalization	NA weeks Due to smaller number of participants with an event, data could not be calulated.	NA weeks Due to smaller number of participants with an event, data could not be calulated.

Adverse Events

DB Period: Pamrevlumab

Serious events: 38 serious events

Other events: 83 other events

Deaths: 16 deaths

DB Period: Placebo

Serious events: 37 serious events

Other events: 74 other events

Deaths: 15 deaths

OLE Period: Pamrevlumab

Serious events: 20 serious events

Other events: 21 other events

Deaths: 12 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	DB Period: Pamrevlumab n=183 participants at risk Participants received pamrevlumab 30 mg/kg, administered by IV infusion, every 3 weeks, for a total of up to 17 infusions over 48 weeks in the DB period.	DB Period: Placebo n=188 participants at risk Participants received pamrevlumab-matching placebo, administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks in the DB period.	OLE Period: Pamrevlumab n=86 participants at risk Participants who completed the treatment in DB period and entered in the OLE period, received pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks for up to 48 weeks.
Gastrointestinal disorders Diarrhoea	7.7% 14/183 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.	8.0% 15/188 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.	4.7% 4/86 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.
General disorders Asthenia	6.0% 11/183 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.	3.7% 7/188 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.	4.7% 4/86 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.
General disorders Fatigue	6.0% 11/183 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.	2.7% 5/188 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.	0.00% 0/86 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.
Infections and infestations Bronchitis	4.9% 9/183 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.	6.4% 12/188 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.	0.00% 0/86 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.
Infections and infestations COVID-19	10.9% 20/183 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.	8.5% 16/188 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.	9.3% 8/86 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.
Infections and infestations Nasopharyngitis	7.1% 13/183 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.	7.4% 14/188 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.	4.7% 4/86 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	14.2% 26/183 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.	12.8% 24/188 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.	5.8% 5/86 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	8.7% 16/183 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.	6.4% 12/188 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.	5.8% 5/86 • From first dose of study drug up to Week 104 As pre-specified, All-cause mortality data were collected and reported for all enrolled participants; and Serious and Non-serious adverse events data were collected and reported for all participants who received any dose of study medication.

Additional Information

Clinical Trial Information Desk

FibroGen, Inc.

Phone: (415) 978-1427

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The multisite consortium can publish any time after the data is collected and analyzed by FibroGen. The investigator can only publish after the multisite consortium publishes (or tries to publish and fails). FibroGen has 60 days to review a publication and can extend the embargo up to an additional 120 days (or 180 total).
Publication restrictions are in place

Restriction type: OTHER