Galapagos Completes Enrollment in Phase 2a Trial Testing GLPG1690 in Diffuse Cutaneous Scleroderma

A Phase 2a clinical trial designed to test Galapagos‘ investigational oral therapy GLPG1690 in people with diffuse cutaneous scleroderma has completed enrolling participants, the company announced.

GLPG1690 is a small molecule that targets and blocks autotaxin. This enzyme is responsible for the production of lysophosphatidic acid, a promoter of fibrosis (scarring) in the lungs, kidneys, and liver, which also drives the release of pro-inflammatory molecules.

NOVESA (NCT03798366) is a double-blind, placebo-controlled study that will investigate the efficacy, safety, and pharmacological profile of GLPG1690, given as oral tablets, for the treatment of the chronic autoimmune disease.

The trial’s primary goal is to assess the change in the modified Rodnan Skin Score (mRSS) — a measure of skin thickness and an indicator of disease severity — after 24 weeks of treatment. 

It recruited 33 adults who have had symptoms of diffuse cutaneous scleroderma for up to five years. To be included, participants also had to have an mRRS greater than 10 and active disease — defined by a worsening of skin thickening or new areas of skin involvement — within six months of screening. Those with new systemic sclerosis symptoms other than Raynaud’s phenomen two years prior to recruitment also were included.

Efficacy will be assessed via forced vital capacity — the total amount of air one can exhale after a deep breath — and high-resolution computed tomography (HRCT), which is a common imaging technique in lung disease assessment. Participants’ quality of life will be measured with the Scleroderma Health Assessment Questionnaire (SHAQ) and their overall scleroderma disease score with the Combined Response Index for Systemic Sclerosis. 

Top-line results are expected in the second half of 2020. Participants completing NOVESA will be offered the chance to continue treatment in a long-term extension trial. 

“We are excited by the rapid enrollment into NOVESA and look forward to learning the results of GLPG1690’s efficacy and safety in patients with SSc [scleroderma],” Walid Abi-Saab, MD, chief medical officer at Galapagos, said in a press release. 

The Belgium-based company also is assessing GLPG1690 as a potential treatment for idiopathic pulmonary fibrosis (IPF) in two worldwide Phase 3 trials with identical design, named ISABELA1 (NCT03711162) and ISABELA2 (NCT03733444).

These trials were supported by the FLORA Phase 2 study (NCT02738801), which showed that a daily dose of 600 mg of GLPG1690 for 12 weeks improved lung function and was well-tolerated in people with IPF.

“We consider SSc as an important and complementary indication to [IPF],” Abi-Saab said. “Thanks to the broad mechanism of action of ‘1690, which we believe is both anti-inflammatory and anti-fibrotic, this compound has the potential to address the important unmet medical need in SSc.”