NCT04419558

Zephyrus II: Efficacy and Safety Study of Pamrevlumab in Participants With Idiopathic Pulmonary Fibrosis (IPF)

Terminated Phase 3 Results posted Last updated 12 August 2024

What this trial tests

Phase 3 trial testing Pamrevlumab in Idiopathic Pulmonary Fibrosis in 372 participants. Terminated before completion.

Timeline

30 September 2020

Primary endpoint
4 September 2023

4 September 2023

Quick facts

Lead sponsor	Kyntra Bio
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	372
Start date	30 September 2020
Primary completion	4 September 2023
Estimated completion	4 September 2023
Sites	157 locations across Italy, Colombia, Ireland, Poland, South Korea, Lebanon, Denmark, Netherlands

Drugs / interventions tested

• Pamrevlumab — full drug profile →
• Placebo

Conditions studied

• Idiopathic Pulmonary Fibrosis — all drugs for Idiopathic Pulmonary Fibrosis →

Sponsor

Kyntra Bio — full company profile →

Who can join

Adults 40 to 85, any sex, with Idiopathic Pulmonary Fibrosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

DB Period: Change From Baseline in FVC at Week 48 Primary · Baseline, Week 48

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).

Group	Value	95% CI
Pamrevlumab	-0.30	± 0.057
Placebo	-0.33	± 0.059

DB Period: Time to Disease Progression Secondary · Up to Week 48

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.

Group	Value	95% CI
Pamrevlumab	59.0	NA – NA
Placebo	NA	49.4 – NA

DB Period: Change From Baseline in Quantitative Lung Fibrosis (QLF) Volume at Week 48 Secondary · Baseline, Week 48

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.

Group	Value	95% CI
Pamrevlumab	255.14	± 72.028
Placebo	269.15	± 60.898

DB Period: Time to First Occurrence of Any Component of the Clinical Composite Endpoint, Whichever Occurred First Secondary · Up to Week 48

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.

Group	Value	95% CI
Pamrevlumab	NA	59.0 – NA
Placebo	NA	NA – NA

DB Period: Time to First Acute IPF Exacerbation Secondary · Up to Week 48

'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.

Group	Value	95% CI
Pamrevlumab	NA	NA – NA
Placebo	NA	NA – NA

DB Period: Time to All-Cause Mortality Secondary · Up to Week 48

'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.

Group	Value	95% CI
Pamrevlumab	NA	59.0 – NA
Placebo	62.9	NA – NA

DB Period: Time to First Respiratory Hospitalization Secondary · Up to Week 48

'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.

Group	Value	95% CI
Pamrevlumab	NA	NA – NA
Placebo	NA	NA – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug up to Week 104. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

DB Period: Pamrevlumab

Serious: 38/183 (21%)

Deaths: 16/184

DB Period: Placebo

Serious: 37/188 (20%)

Deaths: 15/188

OLE Period: Pamrevlumab

Serious: 20/86 (23%)

Deaths: 12/86

Serious adverse events (65 terms)

Reaction	System	DB Period: Pamrevlumab	DB Period: Placebo	OLE Period: Pamrevlumab
Idiopathic pulmonary fibrosis	Respiratory, thoracic and mediastinal disorders	—	—	—
Pneumonia	Infections and infestations	—	—	—
Respiratory failure	Respiratory, thoracic and mediastinal disorders	—	—	—
and mediastinal disorders	Respiratory, thoracic and mediastinal disorders	—	—	—
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	—	—	—
COVID-19	Infections and infestations	—	—	—
Syncope	Nervous system disorders	—	—	—
Pneumothorax	Respiratory, thoracic and mediastinal disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Acute coronary syndrome	Cardiac disorders	—	—	—
Acute myocardial infarction	Cardiac disorders	—	—	—
Atrioventricular block complete	Cardiac disorders	—	—	—
Cardiac failure	Cardiac disorders	—	—	—
Cardiopulmonary failure	Cardiac disorders	—	—	—
Left ventricular failure	Cardiac disorders	—	—	—
Myocardial infarction	Cardiac disorders	—	—	—
Supraventricular tachycardia	Cardiac disorders	—	—	—
Scleritis	Eye disorders	—	—	—
Pancreatitis acute	Gastrointestinal disorders	—	—	—
Asthenia	General disorders	—	—	—
Multiple organ dysfunction syndrome	General disorders	—	—	—
Non-cardiac chest pain	General disorders	—	—	—
Sudden death	General disorders	—	—	—
Cholecystitis acute	Hepatobiliary disorders	—	—	—
Hepatic cirrhosis	Hepatobiliary disorders	—	—	—

Other adverse events (8 terms — click to expand)

Reaction	System	DB Period: Pamrevlumab	DB Period: Placebo	OLE Period: Pamrevlumab
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—
COVID-19	Infections and infestations	—	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Bronchitis	Infections and infestations	—	—	—
Asthenia	General disorders	—	—	—
Fatigue	General disorders	—	—	—

Most-reported serious reactions: Idiopathic pulmonary fibrosis, Pneumonia, Respiratory failure, and mediastinal disorders, Pulmonary embolism, COVID-19, Syncope, Pneumothorax.

Data from ClinicalTrials.gov NCT04419558 adverse events section.

Sponsor's own description

This is a Phase 3 trial to evaluate the efficacy and safety of 30 milligrams (mg)/kilogram (kg) intravenous (IV) infusions of pamrevlumab administered every 3 weeks as compared to placebo in participants with Idiopathic Pulmonary Fibrosis (IPF). There is a 48-week randomized treatment phase followed by an optional, open-label extension phase.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Idiopathic pulmonary fibrosis: Disease mechanisms and drug development.
   Spagnolo P, Kropski JA, Jones MG, Lee JS, et al · · 2021 · cited 448× · PMID 33359599 · DOI 10.1016/j.pharmthera.2020.107798
2. Targeting fibrosis, mechanisms and cilinical trials.
   Zhao M, Wang L, Wang M, Zhou S, et al · · 2022 · cited 352× · PMID 35773269 · DOI 10.1038/s41392-022-01070-3
3. Antibodies to watch in 2021.
   Kaplon H, Reichert JM. · · 2021 · cited 215× · PMID 33459118 · DOI 10.1080/19420862.2020.1860476
4. Current and Future Treatment Landscape for Idiopathic Pulmonary Fibrosis.
   Bonella F, Spagnolo P, Ryerson C. · · 2023 · cited 100× · PMID 37882943 · DOI 10.1007/s40265-023-01950-0
5. Mitochondrial network dynamics in pulmonary disease: Bridging the gap between inflammation, oxidative stress, and bioenergetics.
   Pokharel MD, Garcia-Flores A, Marciano D, Franco MC, et al · · 2024 · cited 73× · PMID 38295575 · DOI 10.1016/j.redox.2024.103049
6. Meaningful Endpoints for Idiopathic Pulmonary Fibrosis (IPF) Clinical Trials: Emphasis on 'Feels, Functions, Survives'. Report of a Collaborative Discussion in a Symposium with Direct Engagement from Representatives of Patients, Investigators, the National Institutes of Health, a
   Raghu G, Ghazipura M, Fleming TR, Aronson KI, et al · · 2024 · cited 69× · PMID 38174955 · DOI 10.1164/rccm.202312-2213so
7. Regulatory Immune Cells in Idiopathic Pulmonary Fibrosis: Friends or Foes?
   van Geffen C, Deißler A, Quante M, Renz H, et al · · 2021 · cited 65× · PMID 33995390 · DOI 10.3389/fimmu.2021.663203
8. Multifunctional regulatory protein connective tissue growth factor (CTGF): A potential therapeutic target for diverse diseases.
   Fu M, Peng D, Lan T, Wei Y, et al · · 2022 · cited 55× · PMID 35847511 · DOI 10.1016/j.apsb.2022.01.007