Systemic Sclerosis
Conditions
Brief 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.
Interventions
DRUGGLPG1690
Film-coated tablets of GLPG1690 for oral use.
DRUGPlacebo
Film-coated tablets of GLPG1690 matching placebo for oral use.
Sponsors
Galapagos NV
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in mRSS at Week 4 | Baseline, 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. |
| Change From Baseline in mRSS at Week 8 | Baseline, 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. |
| Change From Baseline in mRSS at Week 16 | Baseline, 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. |
| Change From Baseline in mRSS at Week 24 | Baseline, 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Baseline up to end of the study (36 weeks) | 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. |
Countries
Belgium, Germany, Italy, Spain, United Kingdom, United States
Participant flow
Recruitment details
Participants were enrolled at study sites in Belgium, the United States, United Kingdom, Spain, and Italy. The first participant was screened on 14 Jan 2019. The last study visit occurred on 22 Jun 2020.
Pre-assignment details
A total of 40 participants were screened, of whom 33 participants were randomized and treated.
Participants by arm
| Arm | Count |
|---|---|
| GLPG1690 600 mg Participants received GLPG1690 600 mg, orally once daily for 24 weeks. | 21 |
| Placebo Participants received GLPG1690 matching placebo, orally once daily for 24 weeks. | 12 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | GLPG1690 600 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 50.4 years STANDARD_DEVIATION 13.58 | 47.3 years STANDARD_DEVIATION 17.99 | 49.3 years STANDARD_DEVIATION 15.13 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 10 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Modified Rodnan Skin Score (mRSS) | 27.0 units on a scale STANDARD_DEVIATION 8.84 | 22.5 units on a scale STANDARD_DEVIATION 6.24 | 25.3 units on a scale STANDARD_DEVIATION 8.18 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 21 Participants | 11 Participants | 32 Participants |
| Sex: Female, Male Female | 15 Participants | 8 Participants | 23 Participants |
| Sex: Female, Male Male | 6 Participants | 4 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 12 |
| other Total, other adverse events | 20 / 21 | 11 / 12 |
| serious Total, serious adverse events | 2 / 21 | 1 / 12 |
Outcome results
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.
Time frame: Baseline, Week 16
Population: Participants in the FAS were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GLPG1690 600 mg | Change From Baseline in mRSS at Week 16 | -6.8 units on a scale | Standard Error 0.85 |
| Placebo | Change From Baseline in mRSS at Week 16 | -4.8 units on a scale | Standard Error 1.12 |
Comparison: Results were estimated using a mixed-effect model repeated measure using treatment and visit as fixed effects, baseline mRSS score and country as covariates, treatment-visit as interaction terms, and participant as a random effect. The variance-covariance matrix used in the model was compound symmetric.p-value: 0.129895% CI: [-4.8, 0.6]Mixed Models Analysis
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.
Time frame: Baseline, Week 24
Population: Participants in the FAS were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GLPG1690 600 mg | Change From Baseline in mRSS at Week 24 | -8.9 units on a scale | Standard Error 0.87 |
| Placebo | Change From Baseline in mRSS at Week 24 | -6.0 units on a scale | Standard Error 1.11 |
Comparison: Results were estimated using a mixed-effect model repeated measure using treatment and visit as fixed effects, baseline mRSS score and country as covariates, treatment-visit as interaction terms, and participant as a random effect. The variance-covariance matrix used in the model was compound symmetric.p-value: 0.041195% CI: [-5.6, -0.1]Mixed Models Analysis
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.
Time frame: Baseline, Week 4
Population: Participants in the FAS were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GLPG1690 600 mg | Change From Baseline in mRSS at Week 4 | -2.2 units on a scale | Standard Error 0.85 |
| Placebo | Change From Baseline in mRSS at Week 4 | -1.6 units on a scale | Standard Error 1.04 |
Comparison: Results were estimated using a mixed-effect model repeated measure using treatment and visit as fixed effects, baseline mRSS score and country as covariates, treatment-visit as interaction terms, and participant as a random effect. The variance-covariance matrix used in the model was compound symmetric.p-value: 0.675795% CI: [-3.1, 2]Mixed Models Analysis
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.
Time frame: Baseline, Week 8
Population: Participants in the FAS were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GLPG1690 600 mg | Change From Baseline in mRSS at Week 8 | -3.2 units on a scale | Standard Error 0.85 |
| Placebo | Change From Baseline in mRSS at Week 8 | -2.5 units on a scale | Standard Error 1.07 |
Comparison: Results were estimated using a mixed-effect model repeated measure using treatment and visit as fixed effects, baseline mRSS score and country as covariates, treatment-visit as interaction terms, and participant as a random effect. The variance-covariance matrix used in the model was compound symmetric.p-value: 0.607995% CI: [-3.3, 1.9]Mixed Models Analysis
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.
Time frame: Baseline up to end of the study (36 weeks)
Population: Safety analysis set consisted of all randomized participants who received at least 1 dose of investigational product.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GLPG1690 600 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 20 Participants |
| GLPG1690 600 mg | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 2 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 11 Participants |
| Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 1 Participants |