Clinical trial NCT03287414: Study of Pharmacodynamics, Pharmacokinetics, Safety and Tolerability of VAY736 in Patients With Idiopathic Pulmonary Fibrosis
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Keywords: idiopathic pulmonary fibrosis
VAY736
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2017-09-19
Enrollment: 30
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study was to investigate the safety, tolerability and efficacy of VAY736 as potential therapy for the treatment of idiopathic pulmonary fibrosis (IPF).

Detailed description: This was an exploratory (non-confirmatory) randomized, patient-, investigator-, sponsor- blinded, placebo controlled study of VAY736 in IPF patients. This study investigated the safety and efficacy of 300 mg VAY736 administered subcutaneously (s.c.) every 4 weeks for 48 weeks.

Participants were randomized in a 1:1 ratio on top of local standard of care (SOC), to receive VAY736 or placebo. Randomized subjects entered the treatment epoch (for up to 48 weeks), followed by two follow-up epochs: the PK/safety follow-up epoch and the PD/safety follow-up epoch. The PK/safety follow-up epoch lasted for 20 weeks. When the PK/safety follow-up epoch was completed, participants in the placebo arm were discharged from the study; but participants in the active arm (those who had received VAY736) continued into the PD/safety follow-up epoch. Participants in the PD/safety follow-up epoch were followed until B-cell recovery (in the peripheral blood), defined as: B cells \>=50/μL or B cells \>= 80% of baseline (whichever occurred first). If a participant had not recovered his/her B-cells after a period of 2 years from the last dose of VAY736, then this participant was discharged from the study.

Eligibility criteria: Inclusion Criteria:

* A diagnosis of definite or probable IPF within 5 years of the screening visit
* Forced Vital Capacity (FVC) 40-90% predicted (inclusive)
* Diffusing Capacity of the Lungs (DLCO), corrected for hemoglobin, 25-79% predicted (inclusive)
* Forced Expiratory Volume in first second (FEV1)/FVC \>70%
* Unlikely to die from cause other than IPF within the next 3 years, in the opinion of the investigator
* Unlikely to undergo lung transplantation during this trial

Exclusion Criteria:

* Emphysema \> fibrosis on screening high-resolution computed tomography (must be confirmed by central reader)
* History of major organ, hematopoietic stem cell or bone marrow transplant
* Clinically diagnosed acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) or other significant clinical worsening within 3 months of randomization
* New York Heart Association (NYHA) class III/IV Congestive Heart Failure (CHF), Ejection Fraction (EF) \<25%
* Current smoker
* 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)

Primary outcomes:
measure: Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Forced Vital Capacity (FVC).
timeFrame: From baseline up to 48 weeks post first dose of study treatment
Secondary outcomes:
measure: Percentage of Participants With All-cause Mortality Events
timeFrame: Up to 48 weeks post first dose of study treatment
measure: Percentage of Participants With Survival Idiopathic Pulmonary Fibrosis (IPF) -Related Mortality Events
timeFrame: Up to 48 weeks post first dose of study treatment
measure: Percentage of Participants With Progression-free Survival (PFS) Events
timeFrame: Up to 48 weeks post first dose of study treatment
measure: Percentage of Participants With Disease Progression Events
timeFrame: Up to 48 weeks post first dose of study treatment
measure: Percentage of Participants With Composite Events
timeFrame: Up to 48 weeks post first dose of study treatment
measure: Change From Baseline to End of Treatment Epoch (48 Weeks of Treatment) in Diffusing Capacity of the Lungs
timeFrame: From baseline up to 48 weeks post first dose of study treatment
measure: Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in 6-minute Walk Distance (6MWD)
timeFrame: From baseline up to 48 weeks post first dose of study treatment
measure: Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Distance Saturation Product
timeFrame: From baseline up to 48 weeks post first dose of study treatment
measure: Change From Baseline to the End of Treatment Epoch (48 Weeks of Treatment) in Resting Oxygen Saturation Level (on Room Air)
timeFrame: From baseline up to 48 weeks post first dose of study treatment
measure: Number of Participants With Positive Serum Anti-VAY736 Antibodies
timeFrame: Day 1, 29, 85, 169, 253 and 337
measure: Ctrough of VAY736 From the Serum Concentration-time Data
timeFrame: At pre-dose on Day 1, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309 and 337
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Aurora
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Durham
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Pittsburgh
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Nashville
country: United States
facility: Novartis Investigative Site
state: Tennessee
city: Salt Lake City
country: United States
facility: Novartis Investigative Site
state: Utah
city: Calgary
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Coswig
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Dublin
country: Ireland
facility: Novartis Investigative Site
city: Forli
country: Italy
facility: Novartis Investigative Site
state: FC
city: Modena
country: Italy
facility: Novartis Investigative Site
state: MO
city: Siena
country: Italy
facility: Novartis Investigative Site
state: SI
city: Cambridge
country: United Kingdom
facility: Novartis Investigative Site
state: Cambridgeshire
city: High Heaton
country: United Kingdom
facility: Novartis Investigative Site
state: Newcastle Upon Tyne
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: