Study of Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of VAY736 in Patients With Idiopathic Pulmonary Fibrosis

• ClinicalTrials.gov Identifier: NCT03287414
• Recruitment Status: Terminated
• First Posted: September 19, 2017
• Last Update Posted: March 14, 2022
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

This study will investigate the safety and efficacy of VAY736 administered subcutaneously (s.c.) every 4 weeks for 48 weeks. Approximately, 84 subjects will be randomized in a 1:1 ratio on top of local standard of care (SOC), to receive VAY736 or placebo.

Condition or disease	Intervention/treatment	Phase
Idiopathic Pulmonary Fibrosis	Drug: VAY736; Drug: Placebo; Drug: Standard of Care (SoC)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: A subject-, investigator-, and sponsor-blinded
• Primary Purpose: Treatment
• Official Title: A Subject-, Investigator-, and Sponsor-blinded, Randomized, Placebo-controlled, Multicenter Study to Investigate Efficacy, Safety, and Tolerability of VAY736 in Patients With Idiopathic Pulmonary Fibrosis
• Actual Study Start Date: December 20, 2017
• Actual Primary Completion Date: November 25, 2020
• Actual Study Completion Date: October 20, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: VAY736; VAY736 administered subcutaneously (s.c.) every 4 weeks	Drug: VAY736; VAY736 administered subcutaneously (s.c.) every 4 weeks; Drug: Standard of Care (SoC); nintedanib, pirfenidone, or neither
Placebo Comparator: Placebo; Placebo administered subcutaneously (s.c.) every 4 weeks	Drug: Placebo; Placebo administered s.c. every 4 weeks; Drug: Standard of Care (SoC); nintedanib, pirfenidone, or neither

Outcome Measures

Primary Outcome Measures :

1. Change from baseline to end of treatment epoch (48 weeks of treatment) in Forced Vital Capacity (FVC). [ Time Frame: Baseline, Week 48 ]
   To assess the efficacy of VAY736 in patients with idiopathic pulmonary fibrosis Change from baseline to end of treatment epoch (48 weeks of treatment) in Forced Vital Capacity (FVC).

Secondary Outcome Measures :

1. All-Cause mortality [ Time Frame: Week 48 ]
   To assess the impact of VAY736 on survival: All-cause mortality
2. Progression-free survival (PFS) [ Time Frame: Week 48 ]

   Progression free survival analysis as defined will be produced at the end of the treatment epoch (week 48) for the following event of interest:

   1. Events, defined as: death (all-cause mortality) OR "progression" (relative reduction in FVC ≥ 10%)
   2. Events, defined as: death (IPF-related mortality) OR "progression" (relative reduction in FVC ≥ 10%)
3. Disease progression [ Time Frame: Week 48 ]
   Disease Progression, defined as: a)relative reduction in FVC ≥ 10% b) relative reduction in Diffusing Capacity of the Lungs (DLCO) ≥ 15% c) absolute reduction in Six Minute Walk Distance (6MWD) ≥ 50 m
4. Composite Endpoint [ Time Frame: Week 48 ]

   Composite Endpoint defined as:

   1. death (all-cause mortality), OR relative reduction in FVC≥10%, OR relative reduction in DLCO ≥15%, OR relative reduction in 6MWD ≥50m
   2. death (IPF-related morality), OR relative reduction in FVC≥10%, OR relative reduction in DLCO ≥15%, OR relative reduction in 6MWD ≥50m
5. Change from baseline to end of treatment epoch (Week 48) in Diffusing Capacity of the Lungs (DLCO) [ Time Frame: Baseline, Week 48 ]
   To assess the impact of VAY736 on Pulmonary Physiology: Change from baseline to theend of treatment epoch (week 48) in DLCO
6. Change from baseline to the end of treatment epoch (Week 48) in 6-minute walk test and in distance-saturation product [ Time Frame: Baseline, Week 48 ]
   Change from baseline to the end of treatment epoch (Week 48) in 6-minute walk test and in distance-saturation product to assess the impact of VAY736 on exercise capacity
7. Change from baseline to the end of treatment epoch (Week 48) in resting oxygen saturation (on room air) [ Time Frame: Baseline, Week 48 ]
   Change from baseline to the end of treatment epoch (Week 48) in resting oxygen saturation (on room air) to assess the impact of VAY736 on gas exchange
8. Immunogenicity of VAY736 [ Time Frame: Week 48 ]
   To assess the immunogenicity of VAY736 by measuring Serum anti-VAY736 antibodies
9. To assess the pharmacokinetics Cmin,ss of VAY736 after multiple s.c. doses [ Time Frame: Day 1 through Week 69 ]
   Determine the Cmin,ss from the serum concentration (VAY736)-time data
10. Idiopathic Pulmonary Fibrosis (IPF) -related Mortality [ Time Frame: Week 48 ]
    To assess the impact of VAY736 on survival: IPF-related mortality

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. A diagnosis of definite or probable IPF within 5 years of the screening visit, as defined by Figure 3, Tables 4-6 of the ATS/ERS/JRS/ALAT Diagnostic Guidelines (Raghu et al 2011)
2. FVC 40-90% predicted (inclusive)
3. DLCO, corrected for hemoglobin, 25-79% predicted (inclusive)
4. FEV1/FVC >70%
5. Unlikely to die from cause other than IPF within the next 3 years, in the opinion of the investigator
6. Unlikely to undergo lung transplantation during this trial

Exclusion Criteria:

1. Emphysema > fibrosis on screening HRCT (must be confirmed by central reader)
2. History of major organ, hematopoietic stem cell or bone marrow transplant
3. Clinically diagnosed AE-IPF or other significant clinical worsening within 3 months of randomization
4. New York Heart Association (NYHA) class III/IV Congestive Heart Failure (CHF), Ejection Fraction (EF) <25%
5. Current smoker
6. Prior use of any B-cell depleting therapy (e.g., rituximab, ofatumumab, or other anti-CD20 mAb, anti-CD40, anti-CD19,anti-CD22 mAb, anti-CD52 mAb, or anti-BAFF mAb)

Other protocol-defined inclusion/exclusion criteria may apply.

Contacts and Locations

Locations

United States, Alabama

Novartis Investigative Site

Birmingham, Alabama, United States, 35294-0007

United States, Colorado

Novartis Investigative Site

Aurora, Colorado, United States, 80045

United States, Florida

Novartis Investigative Site

Miami, Florida, United States, 33136

United States, North Carolina

Novartis Investigative Site

Durham, North Carolina, United States, 27710

United States, Pennsylvania

Novartis Investigative Site

Pittsburgh, Pennsylvania, United States, 15213

United States, Tennessee

Novartis Investigative Site

Nashville, Tennessee, United States, 37203

United States, Utah

Novartis Investigative Site

Salt Lake City, Utah, United States, 84108

Canada, Alberta

Novartis Investigative Site

Calgary, Alberta, Canada, T2N 2T9

Germany

Novartis Investigative Site

Coswig, Germany, 01640

Novartis Investigative Site

Hannover, Germany, 30625

Ireland

Novartis Investigative Site

Dublin, Ireland, D04

Italy

Novartis Investigative Site

Forli, Forli - Cesena, Italy, 47100

Novartis Investigative Site

Modena, Italy, 41124

Novartis Investigative Site

Siena, Italy, 53100

United Kingdom

Novartis Investigative Site

Cambridge, Cambridgeshire, United Kingdom, CB23 3RE

Novartis Investigative Site

High Heaton, Newcastle Upon Tyne, United Kingdom, NE7 7DN

Sponsors and Collaborators

Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03287414
• Other Study ID Numbers: CVAY736X2207
• First Posted: September 19, 2017
• Last Update Posted: March 14, 2022
• Last Verified: March 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

idiopathic pulmonary fibrosis; VAY736

Additional relevant MeSH terms:

Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis; Pathologic Processes; Lung Diseases; Respiratory Tract Diseases