A Clinical Study to Test How Effective and Safe GLPG1690 is for Participants With Systemic Sclerosis

Systemic Sclerosis Clinical Trial

— NOVESA  

Official title:

A Phase 2a, Randomized, Double-blind, Placebo-controlled, Multi-center Study to Evaluate the Efficacy, Safety, and Tolerability of Orally Administered GLPG1690 for 24 Weeks in Subjects With Systemic Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03798366
• Other study ID #: GLPG1690-CL-204
• Secondary ID: 2018-001817-33
• Status: Completed
• Phase: Phase 2
• Start date: January 14, 2019
• Est. completion date: June 22, 2020

Study information

• Verified date: April 2021
• Source: Galapagos NV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main purpose of the study is to see if GLPG1690 helps (together with the standard of care treatment) in the treatment of the skin and other areas affected by systemic sclerosis.

Another aim is to find out how safe/well tolerated GLPG1690 will be and whether there are any side effects. The study will also look at other things, including whether the study drug affects disease progression and also if it changes any aspect of the quality of life.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 33
• Est. completion date: June 22, 2020
• Est. primary completion date: May 21, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Able and willing to comply with the protocol requirements and to sign the informed consent form (ICF) as approved by the Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to any screening evaluations.

• Male and female participants =18 years at the time of consent who meet the American College of Rheumatology (ACR)/EULAR 2013 diagnostic criteria for systemic sclerosis with diffuse cutaneous involvement (according to LeRoy's criteria) and =5 years since the onset of the first systemic sclerosis manifestation other than Raynaud's phenomenon.

• Modified Rodnan Skin Score (mRSS) >10 at screening.

• Active disease at screening, as defined by: Worsening of skin thickening (=2 mRSS points) as assessed by mRSS measured at screening versus a previous mRSS assessment made within 6 months prior to screening, or new areas of skin involvement within 6 months prior to screening as documented by physician note, or new-onset systemic sclerosis with symptoms or signs other than Raynaud's phenomenon within 2 years prior to screening, or =1 tendon friction rub (palpated in the finger flexors or extensors, wrist flexors or extensors, olecranon bursa, shoulders, knees, anterior or posterior ankles with active motion).

• Participant must be able and willing to comply with restrictions on prior and concomitant medication as described in the protocol

• Female participants of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at the baseline visit.

• Female participants of childbearing potential or male participants with female partners of childbearing potential must be willing to comply with the contraceptive methods described in the protocol prior to the first dose of the investigational medicinal product (IMP), during the clinical study, and for at least 90 days after the last dose of the IMP for male participants and 30 days after the last dose of the IMP for female participants.

• A body mass index (BMI) between 18-35 kg/m^2, inclusive, at screening.

• Judged to be in good health by the investigator based upon the results of a medical history, physical examination, vital signs, 12-lead electrocardiogram (ECG), and fasting clinical laboratory safety tests. Clinical laboratory safety test results must be within the reference ranges or test results that are outside the reference ranges need to be considered non-clinically significant in the opinion of the investigator.

Exclusion Criteria:

• Known hypersensitivity to IMP ingredients or history of a significant allergic reaction to any drug as determined by the investigator, such as anaphylaxis requiring hospitalization.

• Breastfeeding female or participant intending to become pregnant or breastfeed.

• History of or a current immunosuppressive condition (e.g. human immunodeficiency virus [HIV] infection, congenital, acquired).

• Positive blood testing for hepatitis B surface antigen or hepatitis C virus (antibody, confirmed by hepatitis C virus ribonucleic acid [RNA] positivity). Note: Participants with a resolved hepatitis A at least 3 months prior to screening can be screened.

• History of malignancy within the past 5 years (except for carcinoma in situ of the uterine cervix, basal cell carcinoma of the skin that has been treated with no evidence of recurrence, prostate cancer medically managed through active surveillance or watchful waiting, and squamous cell carcinoma of the skin if fully resected and ductal carcinoma in situ).

• Clinically significant abnormalities, in the opinion of the investigator, detected on ECG at screening of either rhythm or conduction, QT interval corrected for heart rate using Fridericia's formula (QTcF) >450 ms, or a known long QT syndrome.

• Unstable cardiovascular, pulmonary, or other disease (other than systemic sclerosis-related), in the opinion of the investigator, within 6 months prior to the baseline visit (e.g. coronary heart disease, heart failure, stroke).

• Severe pulmonary disease with forced vital capacity (FVC) =45% of predicted within 6 months prior to the baseline visit.

• Chronic or ongoing active infectious disease, including tuberculosis (requiring hospitalization or systemic treatment within 4 weeks prior to the baseline visit).

• Abnormal liver function test (LFT) at screening, defined as aspartate aminotransferase (AST), and/or alanine aminotransferase (ALT), and/or bilirubin, and/or alkaline phosphatase >2x upper limit of normal (ULN). Retesting is allowed once.

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

Drug:
• GLPG1690
Film-coated tablets of GLPG1690 for oral use.
• Placebo
Film-coated tablets of GLPG1690 matching placebo for oral use.

Locations

Country	Name	City	State
Belgium	UZ Gent	Gent
Belgium	UZ Leuven	Leuven
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Frankfurt	Frankfurt
Italy	Azienda Ospedaliero	Firenze
Italy	Ospedale San Raffaele S.r.l. - PPDS	Milano
Spain	Hospital Universitario Vall d'Hebron - PPDS	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Nuestra Señora de Valme	Sevilla
United Kingdom	University Hospital Aintree	Liverpool
United Kingdom	Royal Free Hospital	London
United States	University of Michigan	Ann Arbor	Michigan
United States	RASF Clinical Research Center	Boca Raton	Florida
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Metroplex Clinical Research Center	Dallas	Texas
United States	UT Physicians Center for Autoimmunity	Houston	Texas
United States	Pacific Arthritis Care Center	Los Angeles	California
United States	UCLA Rheumatology	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Galapagos NV

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in mRSS at Week 4	The mRSS is a validated physical examination method for estimating skin thickness. The 17 body site mRSS was used, with each body site assessed on a scale of 0 (uninvolved) to 3 (severe thickening) with a total score range from 0 (best) to 51 (worst), with higher scores indicating greater severity of skin thickening.	Baseline, Week 4
Primary	Change From Baseline in mRSS at Week 8	The mRSS is a validated physical examination method for estimating skin thickness. The 17 body site mRSS was used, with each body site assessed on a scale of 0 (uninvolved) to 3 (severe thickening) with a total score range from 0 (best) to 51 (worst), with higher scores indicating greater severity of skin thickening.	Baseline, Week 8
Primary	Change From Baseline in mRSS at Week 16	The mRSS is a validated physical examination method for estimating skin thickness. The 17 body site mRSS was used, with each body site assessed on a scale of 0 (uninvolved) to 3 (severe thickening) with a total score range from 0 (best) to 51 (worst), with higher scores indicating greater severity of skin thickening.	Baseline, Week 16
Primary	Change From Baseline in mRSS at Week 24	The mRSS is a validated physical examination method for estimating skin thickness. The 17 body site mRSS was used, with each body site assessed on a scale of 0 (uninvolved) to 3 (severe thickening) with a total score range from 0 (best) to 51 (worst), with higher scores indicating greater severity of skin thickening.	Baseline, Week 24
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs	An adverse event (AE) was any untoward medical occurrence in a participant administered study drug and which did not necessarily have a causal relationship with study drug. A treatment-emergent adverse event (TEAE) is any AE with an onset date on or after the start of stud drug intake and no later than 30 days after last dose of study drug, or any worsening of any AE on or after the start of stud drug intake. A serious AE was defined as an AE that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was medically significant.	Baseline up to end of the study (36 weeks)