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

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03287414
• Collaborator: (none)
• Enrollment: 30
• Locations: 16
• Arms: 2
• Actual Duration (Months): 46
• Patients Per Site: 1.9
• Patients Per Site Per Month: 0

Study Details

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
• 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: Dec 20, 2017
• Actual Primary Completion Date: Nov 25, 2020
• Actual Study Completion Date: Oct 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). [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 [Week 48]

   To assess the impact of VAY736 on survival: All-cause mortality

2. Progression-free survival (PFS) [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: Events, defined as: death (all-cause mortality) OR "progression" (relative reduction in FVC ≥ 10%) Events, defined as: death (IPF-related mortality) OR "progression" (relative reduction in FVC ≥ 10%)

3. Disease progression [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 [Week 48]

   Composite Endpoint defined as: death (all-cause mortality), OR relative reduction in FVC≥10%, OR relative reduction in DLCO ≥15%, OR relative reduction in 6MWD ≥50m 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) [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 [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) [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 [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 [Day 1 through Week 69]

   Determine the Cmin,ss from the serum concentration (VAY736)-time data

10. Idiopathic Pulmonary Fibrosis (IPF) -related Mortality [Week 48]

    To assess the impact of VAY736 on survival: IPF-related mortality

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Birmingham	Alabama	United States	35294-0007
2	Novartis Investigative Site	Aurora	Colorado	United States	80045
3	Novartis Investigative Site	Miami	Florida	United States	33136
4	Novartis Investigative Site	Durham	North Carolina	United States	27710
5	Novartis Investigative Site	Pittsburgh	Pennsylvania	United States	15213
6	Novartis Investigative Site	Nashville	Tennessee	United States	37203
7	Novartis Investigative Site	Salt Lake City	Utah	United States	84108
8	Novartis Investigative Site	Calgary	Alberta	Canada	T2N 2T9
9	Novartis Investigative Site	Coswig		Germany	01640
10	Novartis Investigative Site	Hannover		Germany	30625
11	Novartis Investigative Site	Dublin		Ireland	D04
12	Novartis Investigative Site	Forli	Forli - Cesena	Italy	47100
13	Novartis Investigative Site	Modena		Italy	41124
14	Novartis Investigative Site	Siena		Italy	53100
15	Novartis Investigative Site	Cambridge	Cambridgeshire	United Kingdom	CB23 3RE
16	Novartis Investigative Site	High Heaton	Newcastle Upon Tyne	United Kingdom	NE7 7DN

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03287414
• Other Study ID Numbers: CVAY736X2207
• First Posted: Sep 19, 2017
• Last Update Posted: Mar 14, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: idiopathic pulmonary fibrosis; VAY736
• Additional relevant MeSH terms: Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis

Study Results

No Results Posted as of Mar 14, 2022