Rheumatoid Arthritis
Conditions
Keywords
Arthritis, Rheumatic Diseases, Moderately active rheumatoid arthritis, Severely active rheumatoid arthritis, Joint Diseases, Autoimmune Diseases, Musculoskeletal Diseases, Musculoskeletal and connective tissue disorders
Brief summary
The primary objective of this study was to evaluate the effect of GLPG3970 compared to placebo on the signs and symptoms of Rheumatoid Arthritis (RA) in participants with moderately to severely active RA and an inadequate response to methotrexate (MTX).
Interventions
DRUGGLPG3970
GLPG3970 powder and solvent for oral solution to be reconstituted prior to use.
DRUGPlacebo
Placebo powder and solvent for oral solution to be reconstituted prior to 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 64 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. A body mass index (BMI) between 18-32 kg/m\^2, inclusive. 2. Diagnosis of RA ≥6 months prior to screening AND meeting the 2010 American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) criteria of RA AND ACR functional class I-III. 3. Have ≥6 swollen joints (from a swollen joint count evaluated in 66 joints \[SJC66\]) AND ≥8 tender joints (from a tender joint count evaluated in 68 joints \[TJC68\]) at screening and at the baseline visit (Visit 1) prior to the first investigational product (IP) dosing. 4. DAS28 (CRP) \>3.2 (moderate disease) at screening. 5. Screening serum high sensitivity C-reactive protein (hsCRP) \> upper limit of normal (ULN, central laboratory reference: ≤ 5.0 mg/L). 6. Inadequate response to MTX, i.e. treatment-experienced participants who demonstrated inadequate clinical response during treatment with MTX. 7. Have received MTX for ≥6 months and on stable dose (10 to 20 mg/week) of MTX for at least 4 weeks prior to screening and willing to continue on their current stable dose and dosing regimen for the duration of the study. 8. If taking systemic steroids, prednisone equivalent at a dose of ≤10 mg/day and stable for at least 4 weeks prior to the first IP dosing. Key
Exclusion criteria
1. Current therapy with any conventional disease-modifying antirheumatic drug (DMARD) other than MTX, including 1. oral or injectable gold, sulfasalazine, antimalarials, azathioprine, or D-penicillamine within 4 weeks prior to screening, 2. cyclosporine within 8 weeks prior to screening, and 3. leflunomide within 3 months prior to screening or a minimum 4 weeks prior to screening if after 11 days of standard cholestyramine therapy. 2. Current or previous treatment with a biologic DMARD (bDMARD). Except for participants who received bDMARDs only in a single clinical study setting: 1. For whom the last dose of bDMARD ≥6 months prior to screening (12 months for rituximab or other lymphocyte depleting agents), AND; 2. For whom the bDMARD was effective, without being discontinued due to lack of efficacy. 3. Participants who received an intra-articular or parenteral corticosteroid injection within 4 weeks prior to screening. 4. Participants who received a prior surgical intervention within 12 weeks prior to screening or likely requirement for surgery during the study. 5. Participant has a history of tuberculosis (TB) diagnosis or evidence of active or latent infection with Mycobacterium tuberculosis as defined by one of the following assessments: 1. Positive QuantiFERON-TB Gold test result at screening, OR 2. Chest radiograph (posterior anterior view) taken within 12 weeks prior to screening, read by a qualified radiologist or pulmonologist, with evidence of current active TB or old inactive TB. 6. Participant has any active systemic infection within the last 2 weeks prior to first IP dosing, or poorly controlled chronic cardiac, pulmonary or renal disease. 7. Participant has a known or suspected history of or a current immunosuppressive condition, or a history of invasive opportunistic infections (e.g. human immunodeficiency virus \[HIV\] infection, histoplasmosis, listeriosis, coccidiodmycosis, pneumocystosis, aspergillosis). 8. Participant has a chronic hepatitis B virus (HBV) infection, as defined by persistent HBV surface antigen (HBsAg) positivity. Participant has hepatitis C virus (HCV) infection, as defined by positive HCV antibody at screening and detectable HCV viremia. Participants with positive HCV antibody must undergo reflex HCV ribonucleic acid (RNA) testing, and participants with HCV RNA positivity will be excluded. Participants with positive HCV antibody and negative HCV RNA are eligible. 9. Participant testing positive at screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as detected by real time polymerase chain reaction (RT-PCR), participants presenting any signs or symptoms as detected at baseline following careful physical examination (e.g. cough, fever, headaches, fatigue, dyspnea, myalgia, anosmia, dysgeusia, anorexia, sore throat, others) or reporting any signs and symptoms for the 2 preceding weeks, or participants who have been exposed to individuals with confirmed or suspected diagnosis of SARS-CoV-2 within 2 weeks prior to baseline. In addition, any other locally applicable standard diagnostic criteria may also apply to rule out SARS-CoV-2 infection. Note: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in DAS-28 (CRP) at Week 6 | Baseline and Week 6 | The DAS28 (CRP) is a derived measurement with differential weighting given to each component such as TJC28, SJC28, patient's global assessment of disease activity, and serum CRP level. * TJC28 ranges from 0-28 * SJC28 ranges from 0-28 * High sensitivity C-reactive protein (hsCRP) (in mg/L) * Patient's disease activity VAS (in mm) (ranges from 0 = best to 100 = worst) The DAS28 (CRP) score was calculated using the below formula: DAS28 (CRP) = 0.56 x square root of TJC28 + 0.28 x square root of SJC28 + 0.36 x Ln\[1+CRP(in mg/L)\] + 0.014 x patient's disease activity VAS (in mm) + 0.96. A lower score is considered as better disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events | From first dose of study drug until end of the study (up to 8 weeks) | Treatment-Emergent Adverse Events (TEAE) were defined as * Any adverse event (AE) with an onset date on or after the IP start date and no later than 14 days after last dose of IP, or worsening of any AE on or after the IP start date. * Improvement or no change of any ongoing AEs on or after the IP start date are not considered treatment-emergent. If an AE was ongoing at the time of first IP intake and if there was no change or an improvement in its toxicity grade or its seriousness status, this AE was not considered as treatment-emergent. Serious TEAE was defined as a TEAE that * Resulted in death and was life-threatening; * Required in-patient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly / birth defect; * Was medically significant; |
| Plasma Concentration (Ctrough) of GLPG3970 | Day 15: pre-dose; Day 29: pre-dose; Day 43: pre-dose | Ctrough was defined as plasma concentration level at the end of the dosing interval. |
Countries
Bulgaria, Georgia, Poland, Ukraine
Participant flow
Recruitment details
Study was conducted across 4 countries (Georgia, Poland, Bulgaria, and Ukraine). A total of 54 participants were screened, out of which 28 were randomized and treated.
Pre-assignment details
Participants remained on a stable dose (10 to 20 mg/week) of MTX as background medication.
Participants by arm
| Arm | Count |
|---|---|
| GLPG3970 Participants received 400 mg GLPG3970 oral solution, QD for a period of 6 weeks. | 16 |
| Placebo Participants received GLPG3970 matching placebo oral solution, QD for a period of 6 weeks. | 12 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Physician Decision | 1 | 0 |
Baseline characteristics
| Characteristic | GLPG3970 | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 45.9 years STANDARD_DEVIATION 11.3 | 41.4 years STANDARD_DEVIATION 8.6 | 44.0 years STANDARD_DEVIATION 10.3 |
| Disease Activity Score Based on 28 Joints C-reactive Protein [DAS28 (CRP)] | 6.13 Score on a scale STANDARD_DEVIATION 0.87 | 5.68 Score on a scale STANDARD_DEVIATION 0.88 | 5.93 Score on a scale STANDARD_DEVIATION 0.89 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 12 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 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 | 16 Participants | 12 Participants | 28 Participants |
| Sex: Female, Male Female | 11 Participants | 8 Participants | 19 Participants |
| Sex: Female, Male Male | 5 Participants | 4 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 12 |
| other Total, other adverse events | 6 / 16 | 2 / 12 |
| serious Total, serious adverse events | 0 / 16 | 0 / 12 |
Outcome results
Primary
Change From Baseline in DAS-28 (CRP) at Week 6
The DAS28 (CRP) is a derived measurement with differential weighting given to each component such as TJC28, SJC28, patient's global assessment of disease activity, and serum CRP level. * TJC28 ranges from 0-28 * SJC28 ranges from 0-28 * High sensitivity C-reactive protein (hsCRP) (in mg/L) * Patient's disease activity VAS (in mm) (ranges from 0 = best to 100 = worst) The DAS28 (CRP) score was calculated using the below formula: DAS28 (CRP) = 0.56 x square root of TJC28 + 0.28 x square root of SJC28 + 0.36 x Ln\[1+CRP(in mg/L)\] + 0.014 x patient's disease activity VAS (in mm) + 0.96. A lower score is considered as better disease activity.
Time frame: Baseline and Week 6
Population: Full analysis set (FAS) consisted of all randomized participants who had been administered at least 1 dose of investigational product. Participants with available data at specified timepoint were included.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| GLPG3970 | Change From Baseline in DAS-28 (CRP) at Week 6 | -1.29 Score on a scale | Standard Error 0.224 |
| Placebo | Change From Baseline in DAS-28 (CRP) at Week 6 | -1.24 Score on a scale | Standard Error 0.258 |
p-value: 0.88590% CI: [-0.66, 0.55]MMRM
Secondary
Number of Participants With Treatment Emergent Adverse Events
Treatment-Emergent Adverse Events (TEAE) were defined as * Any adverse event (AE) with an onset date on or after the IP start date and no later than 14 days after last dose of IP, or worsening of any AE on or after the IP start date. * Improvement or no change of any ongoing AEs on or after the IP start date are not considered treatment-emergent. If an AE was ongoing at the time of first IP intake and if there was no change or an improvement in its toxicity grade or its seriousness status, this AE was not considered as treatment-emergent. Serious TEAE was defined as a TEAE that * Resulted in death and was life-threatening; * Required in-patient hospitalization or prolongation of existing hospitalization; * Resulted in persistent or significant disability/incapacity; * Was a congenital anomaly / birth defect; * Was medically significant;
Time frame: From first dose of study drug until end of the study (up to 8 weeks)
Population: Participants in the safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| GLPG3970 | Number of Participants With Treatment Emergent Adverse Events | Serious TEAE | 0 Participants |
| GLPG3970 | Number of Participants With Treatment Emergent Adverse Events | Treatment related TEAE | 4 Participants |
| GLPG3970 | Number of Participants With Treatment Emergent Adverse Events | TEAE leading to death | 0 Participants |
| GLPG3970 | Number of Participants With Treatment Emergent Adverse Events | TEAEs leading to study drug discontinuation | 2 Participants |
| GLPG3970 | Number of Participants With Treatment Emergent Adverse Events | TEAE | 6 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events | TEAEs leading to study drug discontinuation | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events | TEAE | 2 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events | Serious TEAE | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events | TEAE leading to death | 0 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events | Treatment related TEAE | 1 Participants |
Secondary
Plasma Concentration (Ctrough) of GLPG3970
Ctrough was defined as plasma concentration level at the end of the dosing interval.
Time frame: Day 15: pre-dose; Day 29: pre-dose; Day 43: pre-dose
Population: Pharmacokinetic analysis set (PKAS) consisted all participants who received at least 1 dose of investigational product with available plasma concentration data. Participants with available plasma concentration at specified time point were included.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GLPG3970 | Plasma Concentration (Ctrough) of GLPG3970 | Day 15: Pre-dose | 95.3 Nanogram per milliliter | Geometric Coefficient of Variation 115 |
| GLPG3970 | Plasma Concentration (Ctrough) of GLPG3970 | Day 29: Pre-dose | 103 Nanogram per milliliter | Geometric Coefficient of Variation 73.8 |
| GLPG3970 | Plasma Concentration (Ctrough) of GLPG3970 | Day 43: Pre-dose | 49.8 Nanogram per milliliter | Geometric Coefficient of Variation 697 |