Rationale, design and objectives of two phase III, randomised, placebo-controlled studies of GLPG1690, a novel autotaxin inhibitor, in idiopathic pulmonary fibrosis (ISABELA 1 and 2)

Abstract

Introduction: While current standard of care (SOC) for idiopathic pulmonary fibrosis (IPF) slows disease progression, prognosis remains poor. Therefore, an unmet need exists for novel, well-tolerated agents that reduce lung function decline and improve quality of life. Here we report the design of two phase III studies of the novel IPF therapy, GLPG1690.

Methods and analysis: Two identically designed, phase III, international, randomised, double-blind, placebo-controlled, parallel-group, multicentre studies (ISABELA 1 and 2) were initiated in November 2018. It is planned that, in each study, 750 subjects with IPF will be randomised 1:1:1 to receive oral GLPG1690 600 mg, GLPG1690 200 mg or placebo, once daily, on top of local SOC, for at least 52 weeks. The primary endpoint is rate of decline of forced vital capacity (FVC) over 52 weeks. Key secondary endpoints are week 52 composite endpoint of disease progression or all-cause mortality (defined as composite endpoint of first occurrence of ≥10% absolute decline in per cent predicted FVC or all-cause mortality at week 52); time to first respiratory-related hospitalisation until end of study; and week 52 change from baseline in the St George's Respiratory Questionnaire total score (a quality-of-life measure).

Ethics and dissemination: Studies will be conducted in accordance with Good Clinical Practice guidelines, Declaration of Helsinki principles, and local ethical and legal requirements. Results will be reported in a peer-reviewed publication.

Trial registration numbers: NCT03711162; NCT03733444.

Keywords: interstitial fibrosis; rare lung diseases.

Conflict of interest statement

Competing interests: TMM has received personal fees from AstraZeneca, Bayer, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Galapagos, GlaxoSmithKline, Indalo Therapeutics, Pliant Therapeutics, ProMetic, Roche, Samumed and UCB, and stock options from Apellis outside the submitted work. His institution received grants or research fees from AstraZeneca, GlaxoSmithKline and UCB outside the submitted work. MK reports grants and personal fees from Galapagos during the conduct of the study, and grants and personal fees from Boehringer Ingelheim and Roche outside the submitted work. DJL reports personal fees from Galapagos during the conduct of the study, and personal fees from Philips Respironics, Roche, Sanofi Genzyme and Veracyte, grants and personal fees from Boehringer Ingelheim, FibroGen and Global Blood Therapeutics, unpaid Steering Committee membership for Galecto, and institutional fees for consultancy work from the Pulmonary Fibrosis Foundation outside the submitted work. KKB reports personal fees from Galapagos during the conduct of the study, and conversation under CDA with Genoa, grants from National Heart, Lung, and Blood Institute, and personal fees from Aeolus, AstraZeneca, aTyr, Biogen, Boehringer Ingelheim, Galapagos, Galecto Biotech, MedImmune, Novartis, Roche/Genentech, ProMetic, Patara and Third Pole outside the submitted work. WW reports no personal fees; the University Hospitals Leuven received consultancy fees from Galapagos during the conduct of the study and grants from Boehringer Ingelheim and Roche outside the submitted work. NV, SS, PF and WA-S are employees of, and have received warrants from, Galapagos. AF is an employee of Galapagos. MW reports no personal fees; the Erasmus MC received an advisory board fee from Galapagos, and speaker and advisory board fees from Boehringer Ingelheim and Hoffmann-La Roche outside the submitted work.

Figures

Figure 1

Design of the ISABELA 1 and 2 studies. D, day; EoSA, end-of-study assessment; EoST, end-of-study treatment; FU, follow-up; qd, once daily; V, visit; W, week.