Trial Outcomes & Findings for Early Phase Study to Assess Efficacy and Safety of AZD9567 Versus Prednisolone in Patients With Rheumatoid Arthritis (NCT NCT03368235)

Last Updated: 2020-10-05

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

Baseline (Day 1) and Day 15

Results posted on

2020-10-05

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	AZD9567 Participants received AZD9567 40 milligram (mg) oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
Overall Study STARTED	11	10
Overall Study COMPLETED	11	10
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Early Phase Study to Assess Efficacy and Safety of AZD9567 Versus Prednisolone in Patients With Rheumatoid Arthritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone n=10 Participants Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.	Total n=21 Participants Total of all reporting groups
Age, Continuous	64.5 years STANDARD_DEVIATION 8.41 • n=5 Participants	55.5 years STANDARD_DEVIATION 13.58 • n=7 Participants	60.2 years STANDARD_DEVIATION 11.82 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	5 Participants n=7 Participants	13 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 15

Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.

Outcome measures

Outcome measures
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone n=10 Participants Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
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 0.3460	-2.403 score on a scale Standard Error 0.3373

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone n=10 Participants Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Responses ACR20	63.6 percentage of participants	70.0 percentage of participants
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Responses ACR50	36.4 percentage of participants	70.0 percentage of participants
Percentage of Participants Achieving American College of Rheumatology (ACR) 20, ACR50 and ACR70 Responses ACR70	18.2 percentage of participants	50.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Day 15

Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone n=10 Participants Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
LS Mean Change From Baseline in SJC66 Score at Day 15	-6.24 score on a scale Standard Error 0.894	-6.66 score on a scale Standard Error 0.860

SECONDARY outcome

Timeframe: Baseline and Day 15

Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone n=10 Participants Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
LS Mean Change From Baseline in TJC68 Score at Day 15	-9.02 score on a scale Standard Error 2.463	-7.90 score on a scale Standard Error 2.362

SECONDARY outcome

Timeframe: Baseline and Day 15

Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone n=10 Participants Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
LS Mean Change From Baseline in TJC28 Score at Day 15	-6.12 score on a scale Standard Error 1.251	-6.07 score on a scale Standard Error 1.208

SECONDARY outcome

Timeframe: Baseline and Day 15

Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone n=10 Participants Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
LS Mean Change From Baseline in SJC28 Score at Day 15	-5.14 score on a scale Standard Error 0.653	-5.40 score on a scale Standard Error 0.628

SECONDARY outcome

Timeframe: Baseline and Day 15

Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone n=10 Participants Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
LS Mean Change From Baseline in GH Score at Day 15	-27.7 score on a scale Standard Error 7.26	-37.4 score on a scale Standard Error 7.11

SECONDARY outcome

Timeframe: Baseline and Day 15

Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone n=10 Participants Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
LS Mean Change From Baseline in CRP at Day 15	-10.830 mg per liter (L) Standard Error 2.4207	-15.586 mg per liter (L) Standard Error 2.5245

SECONDARY outcome

Timeframe: Baseline and Day 15

Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone n=10 Participants Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
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	-43.4 score on a scale Standard Error 7.71

SECONDARY outcome

Timeframe: Baseline and Day 15

Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone n=10 Participants Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
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	-40.9 score on a scale Standard Error 4.30

SECONDARY outcome

Timeframe: Baseline and Day 15

Population: The FAS included all participants who were randomized and received at least 1 dose of study treatment.

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.

Outcome measures

Outcome measures
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone n=10 Participants Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
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	-0.571 score on a scale Standard Error 0.1712

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
Area Under the Plasma Concentration-Time Curve Until the Last Quantifiable Concentration (AUClast) of AZD9567	17800 hournanomole per L (hnmol/L) Geometric Coefficient of Variation 35.02	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
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 outcome

Timeframe: 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.

The Cmax of AZD9567 was determined using non-compartmental method.

Outcome measures

Outcome measures
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
Maximum Observed Plasma Concentration (Cmax) of AZD9567	4468 nmol/L Geometric Coefficient of Variation 26.89	—

SECONDARY outcome

Timeframe: 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.

The tmax of AZD9567 was determined using non-compartmental method.

Outcome measures

Outcome measures
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
Time to Reach Maximum Plasma Concentration (Tmax) of AZD9567	0.67 hour Interval 0.33 to 1.03	—

SECONDARY outcome

Timeframe: 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.

The Ctrough of AZD9567 was determined using non-compartmental method before the last dose on Day 15.

Outcome measures

Outcome measures
Measure	AZD9567 n=11 Participants Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
Last Plasma Concentration Measured Before the Last Dose (Ctrough) of AZD9567	NA nmol/L Geometric Coefficient of Variation 95.67 Not calculable due to a zero predose value.	—

Adverse Events

AZD9567

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Prednisolone

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	AZD9567 n=11 participants at risk Participants received AZD9567 40 mg oral suspension and placebo capsules matching with prednisolone, orally once daily, for 2 weeks.	Prednisolone n=10 participants at risk Participants received prednisolone 20 mg oral capsules and placebo oral suspension matching with AZD9567, once daily for 2 weeks.
Psychiatric disorders Depression suicidal	9.1% 1/11 • Number of events 1 • From first administration of study treatment (Day 1) up to 2 weeks after last administration of study treatment, approximately 28 days. The Safety analysis set included all participants who were randomized and received at least 1 dose of study treatment.	0.00% 0/10 • From first administration of study treatment (Day 1) up to 2 weeks after last administration of study treatment, approximately 28 days. The Safety analysis set included all participants who were randomized and received at least 1 dose of study treatment.

Other adverse events

Additional Information

Global Clinical Lead

AstraZeneca

Phone: 1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place