Rheumatoid Arthritis
Conditions
Keywords
rheumatoid arthritis, swollen joints, tender joints, autoimmunity
Brief summary
This is a phase 2a study to be run in 2-3 countries in European Union involving 5-6 sites. It will enroll approximately 80 patients to ensure 40 randomized with active rheumatoid arthritis. The treatment period is 2 weeks and total study duration per patient is approximately 1 month. The study drugs are AZD9567 40 mg (an oral SGRM) and the comparator is prednisolone 20mg. The primary endpoint is DAS28 including evaluation of 28 joints and C-reactive protein. Safety parameters will also be evaluated and a biomarker program is included for future research.
Detailed description
This randomized double blind with double dummy technique phase 2a study will be run in 2-3 EU countries, most likely Sweden, Denmark and The Netherlands involving 5-6 sites. It is estimated that 80-100 patients have to be enrolled to ensure the randomization target of 40. The study population is patients with rheumatoid arthritis on stable treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs) with an active flare. It is a two-arm parallel study and the randomization ratio is 1:1 to the two weeks of once daily treatment of 40 mg of AZD9567 and 20 mg prednisolone. The primary objective is to assess the efficacy of AZD9567 40 mg, compared to prednisolone 20 mg in patients with active rheumatoid arthritis in spite of stable treatment with conventional and/or s.c/i.v. biological DMARDs and the primary variable is change from baseline in 28 joint Disease Activity Score using CRP (DAS28 - CRP). As secondary variables swollen and tenderness of 66-68 joints and safety variables are also included. For exploratively purposes there is also a biomarker program, collecting blood samples for future research.
Interventions
DRUGAZD9567
oral OD SGRM administered as suspension
DRUGPrednisolone
oral capsules of 20 mg prednisolone administered OD for two weeks
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
Double dummy technique
Intervention model description
Randomized, double blind, parallell arm study with two weeks treatment of AZD9567 or prednisolone
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Established RA diagnosis according to the 2010 American College of Rheumatology (ACR)/EULAR classification or the 1987 criteria 2. Active RA (DAS28-CRP score ≥ 3.2) with at least 3 swollen joints and 3 tender joints using the DAS28 joint count 3. Patients must have be on stable dosing of conventional and/or s.c./i.v biological DMARDs for the last 8 weeks prior to Visit 1 4. CRP levels \>5mg/L at screening if seronegative for Rheumatoid Factor (RF) and Anti-Cyclic Citrullinated Peptide antibody (anti-CCP Ab), or \>2mg/L if seropositive for either marker 5. BMI between 18 and 35 (inclusive) 6. Negative pregnancy test (serum) for female subjects of childbearing potential
Exclusion criteria
1. History or current inflammatory rheumatic disease other than RA (secondary Sjogren's syndrome excluded) 2. History or current clinically important disease which may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study 3. Any clinical contraindications to treatment with steroids 4. Oral or parenteral steroids (beyond study medication) 8 weeks prior to study start and during the study. Stable use and dose of topical and inhaled steroids for longer than 4 w prior to randomization is acceptable 5. Use of any prohibited medication during the study or if the required washout time of such medication was not adhered to 6. History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs with a similar class to study drugs 7. Any concomitant medications that are known to be associated with Torsades de Pointes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Least Square (LS) Mean Change From Baseline in 28 Joint Disease Activity Score Using C-Reactive Protein (DAS28-CRP) at Day 15 | Baseline (Day 1) and Day 15 | The DAS28-CRP is a measure of disease activity in RA. The score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment (PGA) of health (ranging from very well to very poor). The DAS28-CRP was derived as follows: 0.56 x √\[tender joint count 28 (TJC28)\] + 0.28 x √\[swollen joint count 28 (SJC28)\] + 0.014 x global health (GH) + 0.36 x Ln(CRP+1) + 0.96 to produce the overall DAS28-CRP score on a scale ranged from 0-10 with higher score indicating worse RA symptoms. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| LS Mean Change From Baseline in SJC66 Score at Day 15 | Baseline and Day 15 | A total of 66 joints (33 left, 33 right) were evaluated for swelling. The swollen joint count represents the number of joints in which there was synovial fluid and or soft tissue swelling, but not if bony overgrowth was found. A swollen joint was scored as 0 (absent) and 1 (present) for each joint. The SJC66 was calculated as sum of swollen joints with present status on electronic case report form (eCRF). The swollen joint count ranged from 0-66 with higher score indicating disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. |
| LS Mean Change From Baseline in TJC68 Score at Day 15 | Baseline and Day 15 | A total of 68 joints (34 left, 34 right) were evaluated for tenderness. The tender joint count represents the number of joints in which pain was reported. A tender joint was scored as 0 (absent) and 1 (present) for each joint. The TJC68 was calculated as sum of tender joints with present status on eCRF. The tender joint count ranged from 0-68 with higher score indicating disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. |
| LS Mean Change From Baseline in TJC28 Score at Day 15 | Baseline and Day 15 | TJC28 was evaluated as one of the components that comprised the DAS28-score. A total of 28 joints (14 left, 14 right) were evaluated for tenderness as obtained from the joint count right or left eCRF. The tender joint count represents the number of joints in which pain was reported. A tender joint was scored as 0 (absent) and 1 (present) for each joint. The TJC28 was calculated as sum of tender joints with present status on eCRF. The tender joint count ranged from 0-28 with higher score indicating disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. |
| LS Mean Change From Baseline in SJC28 Score at Day 15 | Baseline and Day 15 | SJC28 was evaluated as one of the components that comprised the DAS28-score. A total of 28 joints (14 left, 14 right) were evaluated for swelling as obtained from the joint count right or left eCRF. The swollen joint count represents the number of joints in which there was synovial fluid and or soft tissue swelling, but not if bony overgrowth was found. A swollen joint was scored as 0 (absent) and 1 (present) for each joint. The SJC28 was calculated as sum of swollen joints with present status on eCRF. The swollen joint count ranged from 0-28 with higher score indicating disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. |
| LS Mean Change From Baseline in GH Score at Day 15 | Baseline and Day 15 | GH was evaluated as one of the components that comprised the DAS28-score. Participant's GH was measured using PGA of disease activity by means of the visual analogue scale (VAS). The PGA VAS consists of a 100 millimeter (mm) long scale ranging from 0 (very well) to 100 (very poor). Higher score indicated greater disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. |
| LS Mean Change From Baseline in CRP at Day 15 | Baseline and Day 15 | CRP was evaluated as one of the components that comprised the DAS28-score. The CRP was collected at the local laboratory during screening and central laboratory on Days 1, 8, 15 and 28. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. |
| LS Mean Change From Baseline in Participant's Assessment of Pain Score at Day 15 | Baseline and Day 15 | Participant's assessment of pain score was evaluated as one of the components that comprised the ACR. Participant's assessment of pain score was assessed from the amount of pain due to RA on a VAS ranging from 0 (no pain) to 100 (extreme pain). Higher score indicated greater disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. |
| Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Responses | Day 15 | The ACR20, ACR50 or ACR70 was achieved if there was at least a 20%, 50% or 70% improvement from baseline in swollen joint count 66 (SJC66) and tender joint count 68 (TJC68) and 3 or more of the 5 following assessments: participant's assessment of pain, GH, physician's global assessment of disease activity, participant's assessment of physical function and CRP. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. |
| LS Mean Change From Baseline in Participant's Assessment of Physical Function Score at Day 15 | Baseline and Day 15 | Participant's assessment of physical function score was evaluated as one of the components that comprised the ACR. The participant's assessment of physical function across 8 functional areas was measured by health assessment questionnaire. The total score ranging from 0 (no difficulty) to 24 (inability to perform tasks). Higher score indicated greater disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. |
| Area Under the Plasma Concentration-Time Curve Until the Last Quantifiable Concentration (AUClast) of AZD9567 | Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15. | The AUClast was determined using non-compartmental method and calculated using the linear trapezoidal rule when concentrations were increased and the logarithmic trapezoidal rule when concentrations were decreased. |
| Area Under the Concentration-Time Curve From Time Zero to 6 Hours After Dose (AUC0-6) of AZD9567 | Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15. | The AUC0-6 was determined using non-compartmental method and calculated using the linear trapezoidal rule when concentrations were increased and the logarithmic trapezoidal rule when concentrations were decreased. |
| Maximum Observed Plasma Concentration (Cmax) of AZD9567 | Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15. | The Cmax of AZD9567 was determined using non-compartmental method. |
| Time to Reach Maximum Plasma Concentration (Tmax) of AZD9567 | Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15. | The tmax of AZD9567 was determined using non-compartmental method. |
| Last Plasma Concentration Measured Before the Last Dose (Ctrough) of AZD9567 | Predose on Day 15 | The Ctrough of AZD9567 was determined using non-compartmental method before the last dose on Day 15. |
| LS Mean Change From Baseline in Physician's Global Assessment of Disease Activity Score at Day 15 | Baseline and Day 15 | Physician's global assessment of disease activity score was evaluated as one of the components that comprised the ACR. The physician's global assessment of disease activity was measured on a VAS ranging from 0 (very well) to 100 (very poor). Higher score indicated greater disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment. |
Countries
Netherlands, Sweden
Participant flow
Recruitment details
This was a Phase 2a study conducted in participants with active rheumatoid arthritis (RA) in spite of stable treatment with conventional disease-modifying anti-rheumatic drugs at 5 investigational sites across Sweden and The Netherlands between 18 January 2018 and 12 November 2019.
Pre-assignment details
A total of 21 participants were randomized in a 1:1 ratio to take either AZD9567 or prednisolone in a 2-week double-blind, double-dummy treatment period.
Participants by arm
| Arm | Count |
|---|---|
| AZD9567 Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks. | 11 |
| Prednisolone Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks. | 10 |
| Total | 21 |
Baseline characteristics
| Characteristic | AZD9567 | Prednisolone | Total |
|---|---|---|---|
| Age, Continuous | 64.5 years STANDARD_DEVIATION 8.41 | 55.5 years STANDARD_DEVIATION 13.58 | 60.2 years STANDARD_DEVIATION 11.82 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 10 Participants | 21 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 | 11 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Male | 3 Participants | 5 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 10 |
| other Total, other adverse events | 10 / 11 | 9 / 10 |
| serious Total, serious adverse events | 1 / 11 | 0 / 10 |
Outcome results
Primary
Least Square (LS) Mean Change From Baseline in 28 Joint Disease Activity Score Using C-Reactive Protein (DAS28-CRP) at Day 15
The DAS28-CRP is a measure of disease activity in RA. The score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment (PGA) of health (ranging from very well to very poor). The DAS28-CRP was derived as follows: 0.56 x √\[tender joint count 28 (TJC28)\] + 0.28 x √\[swollen joint count 28 (SJC28)\] + 0.014 x global health (GH) + 0.36 x Ln(CRP+1) + 0.96 to produce the overall DAS28-CRP score on a scale ranged from 0-10 with higher score indicating worse RA symptoms. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment.
Time frame: Baseline (Day 1) and Day 15
Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 | Least Square (LS) Mean Change From Baseline in 28 Joint Disease Activity Score Using C-Reactive Protein (DAS28-CRP) at Day 15 | -1.931 score on a scale | Standard Error 0.346 |
| Prednisolone | Least Square (LS) Mean Change From Baseline in 28 Joint Disease Activity Score Using C-Reactive Protein (DAS28-CRP) at Day 15 | -2.403 score on a scale | Standard Error 0.3373 |
Comparison: MMRM = mixed model repeated measures.p-value: 0.31595% CI: [-0.487, 1.431]MMRM
Secondary
Area Under the Concentration-Time Curve From Time Zero to 6 Hours After Dose (AUC0-6) of AZD9567
The AUC0-6 was determined using non-compartmental method and calculated using the linear trapezoidal rule when concentrations were increased and the logarithmic trapezoidal rule when concentrations were decreased.
Time frame: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15.
Population: The PK analysis set included all participants with at least 1 quantifiable AZD9567 concentration with a documented related dosing history.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 | Area Under the Concentration-Time Curve From Time Zero to 6 Hours After Dose (AUC0-6) of AZD9567 | 17740 h*nmol/L | Geometric Coefficient of Variation 35.34 |
Secondary
Area Under the Plasma Concentration-Time Curve Until the Last Quantifiable Concentration (AUClast) of AZD9567
The AUClast was determined using non-compartmental method and calculated using the linear trapezoidal rule when concentrations were increased and the logarithmic trapezoidal rule when concentrations were decreased.
Time frame: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15.
Population: The Pharmacokinetic (PK) analysis set included all participants with at least 1 quantifiable AZD9567 concentration with a documented related dosing history.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 | Area Under the Plasma Concentration-Time Curve Until the Last Quantifiable Concentration (AUClast) of AZD9567 | 17800 hour*nanomole per L (h*nmol/L) | Geometric Coefficient of Variation 35.02 |
Secondary
Last Plasma Concentration Measured Before the Last Dose (Ctrough) of AZD9567
The Ctrough of AZD9567 was determined using non-compartmental method before the last dose on Day 15.
Time frame: Predose on Day 15
Population: The PK analysis set included all participants with at least 1 quantifiable AZD9567 concentration with a documented related dosing history.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 | Last Plasma Concentration Measured Before the Last Dose (Ctrough) of AZD9567 | NA nmol/L | Geometric Coefficient of Variation 95.67 |
Secondary
LS Mean Change From Baseline in CRP at Day 15
CRP was evaluated as one of the components that comprised the DAS28-score. The CRP was collected at the local laboratory during screening and central laboratory on Days 1, 8, 15 and 28. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment.
Time frame: Baseline and Day 15
Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 | LS Mean Change From Baseline in CRP at Day 15 | -10.830 mg per liter (L) | Standard Error 2.4207 |
| Prednisolone | LS Mean Change From Baseline in CRP at Day 15 | -15.586 mg per liter (L) | Standard Error 2.5245 |
p-value: 0.18795% CI: [-2.514, 12.025]MMRM
Secondary
LS Mean Change From Baseline in GH Score at Day 15
GH was evaluated as one of the components that comprised the DAS28-score. Participant's GH was measured using PGA of disease activity by means of the visual analogue scale (VAS). The PGA VAS consists of a 100 millimeter (mm) long scale ranging from 0 (very well) to 100 (very poor). Higher score indicated greater disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment.
Time frame: Baseline and Day 15
Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 | LS Mean Change From Baseline in GH Score at Day 15 | -27.7 score on a scale | Standard Error 7.26 |
| Prednisolone | LS Mean Change From Baseline in GH Score at Day 15 | -37.4 score on a scale | Standard Error 7.11 |
p-value: 0.32595% CI: [-10.5, 30.1]MMRM
Secondary
LS Mean Change From Baseline in Participant's Assessment of Pain Score at Day 15
Participant's assessment of pain score was evaluated as one of the components that comprised the ACR. Participant's assessment of pain score was assessed from the amount of pain due to RA on a VAS ranging from 0 (no pain) to 100 (extreme pain). Higher score indicated greater disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment.
Time frame: Baseline and Day 15
Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 | LS Mean Change From Baseline in Participant's Assessment of Pain Score at Day 15 | -27.3 score on a scale | Standard Error 8.17 |
| Prednisolone | LS Mean Change From Baseline in Participant's Assessment of Pain Score at Day 15 | -43.4 score on a scale | Standard Error 7.71 |
p-value: 0.14495% CI: [-6, 38.1]MMRM
Secondary
LS Mean Change From Baseline in Participant's Assessment of Physical Function Score at Day 15
Participant's assessment of physical function score was evaluated as one of the components that comprised the ACR. The participant's assessment of physical function across 8 functional areas was measured by health assessment questionnaire. The total score ranging from 0 (no difficulty) to 24 (inability to perform tasks). Higher score indicated greater disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment.
Time frame: Baseline and Day 15
Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 | LS Mean Change From Baseline in Participant's Assessment of Physical Function Score at Day 15 | -0.441 score on a scale | Standard Error 0.1758 |
| Prednisolone | LS Mean Change From Baseline in Participant's Assessment of Physical Function Score at Day 15 | -0.571 score on a scale | Standard Error 0.1712 |
p-value: 0.58995% CI: [-0.37, 0.631]MMRM
Secondary
LS Mean Change From Baseline in Physician's Global Assessment of Disease Activity Score at Day 15
Physician's global assessment of disease activity score was evaluated as one of the components that comprised the ACR. The physician's global assessment of disease activity was measured on a VAS ranging from 0 (very well) to 100 (very poor). Higher score indicated greater disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment.
Time frame: Baseline and Day 15
Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 | LS Mean Change From Baseline in Physician's Global Assessment of Disease Activity Score at Day 15 | -37.0 score on a scale | Standard Error 4.38 |
| Prednisolone | LS Mean Change From Baseline in Physician's Global Assessment of Disease Activity Score at Day 15 | -40.9 score on a scale | Standard Error 4.3 |
p-value: 0.51295% CI: [-8.3, 16]MMRM
Secondary
LS Mean Change From Baseline in SJC28 Score at Day 15
SJC28 was evaluated as one of the components that comprised the DAS28-score. A total of 28 joints (14 left, 14 right) were evaluated for swelling as obtained from the joint count right or left eCRF. The swollen joint count represents the number of joints in which there was synovial fluid and or soft tissue swelling, but not if bony overgrowth was found. A swollen joint was scored as 0 (absent) and 1 (present) for each joint. The SJC28 was calculated as sum of swollen joints with present status on eCRF. The swollen joint count ranged from 0-28 with higher score indicating disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment.
Time frame: Baseline and Day 15
Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 | LS Mean Change From Baseline in SJC28 Score at Day 15 | -5.14 score on a scale | Standard Error 0.653 |
| Prednisolone | LS Mean Change From Baseline in SJC28 Score at Day 15 | -5.40 score on a scale | Standard Error 0.628 |
p-value: 0.75795% CI: [-1.5, 2.03]MMRM
Secondary
LS Mean Change From Baseline in SJC66 Score at Day 15
A total of 66 joints (33 left, 33 right) were evaluated for swelling. The swollen joint count represents the number of joints in which there was synovial fluid and or soft tissue swelling, but not if bony overgrowth was found. A swollen joint was scored as 0 (absent) and 1 (present) for each joint. The SJC66 was calculated as sum of swollen joints with present status on electronic case report form (eCRF). The swollen joint count ranged from 0-66 with higher score indicating disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment.
Time frame: Baseline and Day 15
Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 | LS Mean Change From Baseline in SJC66 Score at Day 15 | -6.24 score on a scale | Standard Error 0.894 |
| Prednisolone | LS Mean Change From Baseline in SJC66 Score at Day 15 | -6.66 score on a scale | Standard Error 0.86 |
p-value: 0.71795% CI: [-1.98, 2.81]MMRM
Secondary
LS Mean Change From Baseline in TJC28 Score at Day 15
TJC28 was evaluated as one of the components that comprised the DAS28-score. A total of 28 joints (14 left, 14 right) were evaluated for tenderness as obtained from the joint count right or left eCRF. The tender joint count represents the number of joints in which pain was reported. A tender joint was scored as 0 (absent) and 1 (present) for each joint. The TJC28 was calculated as sum of tender joints with present status on eCRF. The tender joint count ranged from 0-28 with higher score indicating disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment.
Time frame: Baseline and Day 15
Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 | LS Mean Change From Baseline in TJC28 Score at Day 15 | -6.12 score on a scale | Standard Error 1.251 |
| Prednisolone | LS Mean Change From Baseline in TJC28 Score at Day 15 | -6.07 score on a scale | Standard Error 1.208 |
p-value: 0.97395% CI: [-3.43, 3.32]MMRM
Secondary
LS Mean Change From Baseline in TJC68 Score at Day 15
A total of 68 joints (34 left, 34 right) were evaluated for tenderness. The tender joint count represents the number of joints in which pain was reported. A tender joint was scored as 0 (absent) and 1 (present) for each joint. The TJC68 was calculated as sum of tender joints with present status on eCRF. The tender joint count ranged from 0-68 with higher score indicating disease severity. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment.
Time frame: Baseline and Day 15
Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 | LS Mean Change From Baseline in TJC68 Score at Day 15 | -9.02 score on a scale | Standard Error 2.463 |
| Prednisolone | LS Mean Change From Baseline in TJC68 Score at Day 15 | -7.90 score on a scale | Standard Error 2.362 |
p-value: 0.72495% CI: [-7.69, 5.46]MMRM
Secondary
Maximum Observed Plasma Concentration (Cmax) of AZD9567
The Cmax of AZD9567 was determined using non-compartmental method.
Time frame: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15.
Population: The PK analysis set included all participants with at least 1 quantifiable AZD9567 concentration with a documented related dosing history.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| AZD9567 | Maximum Observed Plasma Concentration (Cmax) of AZD9567 | 4468 nmol/L | Geometric Coefficient of Variation 26.89 |
Secondary
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Responses
The ACR20, ACR50 or ACR70 was achieved if there was at least a 20%, 50% or 70% improvement from baseline in swollen joint count 66 (SJC66) and tender joint count 68 (TJC68) and 3 or more of the 5 following assessments: participant's assessment of pain, GH, physician's global assessment of disease activity, participant's assessment of physical function and CRP. Baseline was defined as the last non-missing assessment (scheduled or unscheduled) prior to the first dose of study treatment.
Time frame: Day 15
Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment. Participants with missing ACR assessment at Day 15 were considered as non-responders in the respective analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AZD9567 | Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Responses | ACR20 | 63.6 percentage of participants |
| AZD9567 | Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Responses | ACR50 | 36.4 percentage of participants |
| AZD9567 | Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Responses | ACR70 | 18.2 percentage of participants |
| Prednisolone | Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Responses | ACR20 | 70.0 percentage of participants |
| Prednisolone | Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Responses | ACR50 | 70.0 percentage of participants |
| Prednisolone | Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Responses | ACR70 | 50.0 percentage of participants |
Comparison: Treatment comparison ACR20: AZD9567 Vs prednisolonep-value: 0.80795% CI: [0.12, 5.34]Regression, Logistic
Comparison: Treatment comparison ACR50: AZD9567 Vs prednisolonep-value: 0.198Fisher Exact
Comparison: Treatment comparison ACR70: AZD9567 Vs prednisolonep-value: 0.183Fisher Exact
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of AZD9567
The tmax of AZD9567 was determined using non-compartmental method.
Time frame: Predose and 0.25, 0.5, 1, 1.5, 2, 3, 4 and 6 hour postdose on Day 15.
Population: The PK analysis set included all participants with at least 1 quantifiable AZD9567 concentration with a documented related dosing history.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| AZD9567 | Time to Reach Maximum Plasma Concentration (Tmax) of AZD9567 | 0.67 hour |