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

Novartis

Status and phase: Terminated; Phase 2

Conditions: Idiopathic Pulmonary Fibrosis

Treatments: Drug: Placebo; Drug: Standard of Care (SoC); Drug: VAY736

Study type: Interventional

Funder types: Industry

Identifiers

NCT03287414

CVAY736X2207

2017 002667 17 (EudraCT Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 40 to 80 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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30 participants in 2 patient groups, including a placebo group

VAY736

Experimental group

Description:

Participants received 300 mg VAY736 administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy

Treatment:

Drug: VAY736

Drug: Standard of Care (SoC)

Placebo

Placebo Comparator group

Description:

Participants received placebo administered subcutaneously every 4 weeks for 48 weeks on top of current standard-of-care therapy

Treatment:

Drug: Standard of Care (SoC)

Drug: Placebo