A 6-month randomised, double-blind, open arm comparator, phase IIb, with AZD9056, in patients with Rheumatoid Arthritis (RA)

Study identifier:D1520C00001

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Randomised, Double-Blind (with Open Comparator Etanercept Limb), Placebo-Controlled, Phase IIb, Multicentre Study to Evaluate the Efficacy of 4 Doses of AZD9056 Administered for 6 Months on the Signs and Symptoms of Rheumatoid Arthritis in Patients with Active Disease Receiving Background Methotrexate or Sulphasalazine

Medical condition

Rheumatoid Arthritis

Phase

Phase 2

Healthy volunteers

Study drug

AZD9056, Etanercept, Placebo

Sex

All

Actual Enrollment

385

Study type

Interventional

Age

18 Years +

Date

Study Start Date: 01 Aug 2007

Primary Completion Date: -

Study Completion Date: 01 Mar 2009

Study design

Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Jan 2013 by AstraZeneca Pharmaceuticals

Collaborators

Inclusion and exclusion criteria

Location

Research Site

BUENOS AIRES, Argentina

Location

Research Site

CORDOBA, Argentina

Location

Research Site

PLANTA BAJA SAN JUAN, Argentina

Location

Research Site

ROSARIO, SANTA FE, Argentina

Location

Research Site

SAN MIGUEL DE TUCUMAN, Argentina

Location

Research Site

VICTORIA PARK, WA, Australia

Location

Research Site

WOODSVILLE, SA, Australia

Location

Research Site

WOOLLOONGABBA, QLD, Australia

Arms	Assigned Interventions
Active Comparator: 1 Etanercept 50mg, subcutaneous, once weekly	-
Experimental: 2 50mg oral, once daily	-
Experimental: 3 100 mg oral, once daily	-
Experimental: 4 200 mg oral, once daily	-
Experimental: 5 400mg once, daily	-
Placebo Comparator: 6 oral, once daily	-

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The first participant enrolled on 01 August 2007, the last participant completed the study on 08 April 2009. Participants were recruited from 59 centres in 12 countries in Australia, Canada, Europe, Russia, South America, and the USA.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Male/female participants with active rheumatoid arthritis (and on background methotrexate or sulphasalazine) were randomly assigned to receive AZD9056 at 50, 100, 200 or 400 mg once daily, placebo or etanercept. It was planned to randomise approximately 360 participants, 60 to the open-label etanercept arm and 300 to the AZD9056 or placebo arms

Reporting Groups

	Description
AZD9056 50 mg	AZD9056 50 mg, oral tablets, once daily, double blinded
AZD9056 100 mg	AZD9056 100 mg, oral tablets, once daily, double blinded
AZD9056 200 mg	AZD9056 200 mg, oral tablets, once daily, double blinded
AZD9056 400 mg	AZD9056 400 mg, oral tablets, once daily, double blinded
Placebo	Placebo to AZD9056, oral tablets, once daily, double blinded
Etanercept	Etanercept 50 mg, subcutaneous injection, once weekly, open label

Participant Flow: Overall Study

	AZD9056 50 mg	AZD9056 100 mg	AZD9056 200 mg	AZD9056 400 mg	Placebo	Etanercept
STARTED	64^[1]	64^[2]	64^[3]	64^[4]	65^[5]	64^[6]
COMPLETED	52^[7]	50^[8]	49^[9]	50^[10]	53^[11]	62^[12]
NOT COMPLETED	12	14	15	14	12	2
Adverse Event	9	3	6	9	7	2
Withdrawal by Subject	0	9	5	2	2	0
Protocol Violation	0	0	1	0	0	0
Lack of Efficacy	1	1	1	2	1	0
Lost to Follow-up	0	0	0	0	1	0
Incorrect enrollment	1	0	1	0	1	0
Oral corticotherapy for acute urticaria	0	1	0	0	0	0
Long break in taking Medication	0	0	0	1	0	0
Did not receive Treatment	1	0	1	0	0	0

[1]	Participants randomised. One of these participants did not subsequently receive treatment.
[2]	Participants randomised.
[3]	Participants randomised. One of these participants did not subsequently receive treatment.
[4]	Participants randomised.
[5]	Participants randomised.
[6]	Participants randomised.
[7]	Participants completed the study.
[8]	Participants completed the study.
[9]	Participants completed the study.
[10]	Participants completed the study.
[11]	Participants completed the study.
[12]	Participants completed the study.

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
AZD9056 50 mg	AZD9056 50 mg, oral tablets, once daily, double blinded
AZD9056 100 mg	AZD9056 100 mg, oral tablets, once daily, double blinded
AZD9056 200 mg	AZD9056 200 mg, oral tablets, once daily, double blinded
AZD9056 400 mg	AZD9056 400 mg, oral tablets, once daily, double blinded
Placebo	Placebo to AZD9056, oral tablets, once daily, double blinded
Etanercept	Etanercept 50 mg, subcutaneous injection, once weekly, open label

Baseline Measures

	AZD9056 50 mg	AZD9056 100 mg	AZD9056 200 mg	AZD9056 400 mg	Placebo	Etanercept	Total
Number of Participants [units: Participants]	63	64	63	64	65	64	383
Age Continuous [units: Years] Mean ± Standard Deviation	52 ± 12.8	54 ± 11.5	50 ± 11.9	52 ± 11.8	51 ± 11.9	51 ± 10.8	51.7 ± 11.76
Gender, Male/Female [units: Participants]
Female	56	54	51	59	54	55	329
Male	7	10	12	5	11	9	54

Outcome Measures

1. Primary Outcome Measure: American College of Rheumatology 20 response (ACR20) at 6 months [ Time Frame: 6 months ]

Measure Type	Primary
Measure Name	American College of Rheumatology 20 response (ACR20) at 6 months
Measure Description	The number of participants with greater to or equal to 20% improvement in the ACR composite score (a measure of RA symptoms including: joint swelling and tenderness; patient’s assessment of pain, disease activity and physical function; physician’s assessment of disease activity; and CRP) after 6 months’ treatment
Time Frame	6 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD9056 50 mg	AZD9056 50 mg, oral tablets, once daily, double blinded
AZD9056 100 mg	AZD9056 100 mg, oral tablets, once daily, double blinded
AZD9056 200 mg	AZD9056 200 mg, oral tablets, once daily, double blinded
AZD9056 400 mg	AZD9056 400 mg, oral tablets, once daily, double blinded
Placebo	Placebo to AZD9056, oral tablets, once daily, double blinded
Etanercept	Etanercept 50 mg, subcutaneous injection, once weekly, open label

Measured Values

	AZD9056 50 mg	AZD9056 100 mg	AZD9056 200 mg	AZD9056 400 mg	Placebo	Etanercept
Number of Participants Analyzed [units:participants]	63	64	63	64	65	64
American College of Rheumatology 20 response (ACR20) at 6 months [units: Participants]	23	26	23	21	21	42

No statistical analysis provided for American College of Rheumatology 20 response (ACR20) at 6 months

2. Secondary Outcome Measure: American College of Rheumatology 50 response (ACR50) at 6 months [ Time Frame: 6 months ]

Measure Type	Secondary
Measure Name	American College of Rheumatology 50 response (ACR50) at 6 months
Measure Description	The number of participants with greater to or equal to 50% improvement in the ACR composite score (a measure of RA symptoms including: joint swelling and tenderness; patient’s assessment of pain, disease activity and physical function; physician’s assessment of disease activity; and CRP) after 6 months’ treatment.
Time Frame	6 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD9056 50 mg	AZD9056 50 mg, oral tablets, once daily, double blinded
AZD9056 100 mg	AZD9056 100 mg, oral tablets, once daily, double blinded
AZD9056 200 mg	AZD9056 200 mg, oral tablets, once daily, double blinded
AZD9056 400 mg	AZD9056 400 mg, oral tablets, once daily, double blinded
Placebo	Placebo to AZD9056, oral tablets, once daily, double blinded
Etanercept	Etanercept 50 mg, subcutaneous injection, once weekly, open label

Measured Values

	AZD9056 50 mg	AZD9056 100 mg	AZD9056 200 mg	AZD9056 400 mg	Placebo	Etanercept
Number of Participants Analyzed [units:participants]	63	64	63	64	65	64
American College of Rheumatology 50 response (ACR50) at 6 months [units: Participants]	13	8	9	13	11	30

No statistical analysis provided for American College of Rheumatology 50 response (ACR50) at 6 months

3. Secondary Outcome Measure: American College of Rheumatology 70 response (ACR70) at 6 months [ Time Frame: 6 months ]

Measure Type	Secondary
Measure Name	American College of Rheumatology 70 response (ACR70) at 6 months
Measure Description	The number of participants with greater to or equal to 70% improvement in the ACR composite score (a measure of RA symptoms including: joint swelling and tenderness; patient’s assessment of pain, disease activity and physical function; physician’s assessment of disease activity; and CRP) after 6 months’ treatment
Time Frame	6 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD9056 50 mg	AZD9056 50 mg, oral tablets, once daily, double blinded
AZD9056 100 mg	AZD9056 100 mg, oral tablets, once daily, double blinded
AZD9056 200 mg	AZD9056 200 mg, oral tablets, once daily, double blinded
AZD9056 400 mg	AZD9056 400 mg, oral tablets, once daily, double blinded
Placebo	Placebo to AZD9056, oral tablets, once daily, double blinded
Etanercept	Etanercept 50 mg, subcutaneous injection, once weekly, open label

Measured Values

	AZD9056 50 mg	AZD9056 100 mg	AZD9056 200 mg	AZD9056 400 mg	Placebo	Etanercept
Number of Participants Analyzed [units:participants]	63	64	63	64	65	64
American College of Rheumatology 70 response (ACR70) at 6 months [units: Participants]	6	7	5	5	3	15

No statistical analysis provided for American College of Rheumatology 70 response (ACR70) at 6 months

4. Secondary Outcome Measure: Disease Activity Score (based on 28 joint count) (DAS28) at 6 months. [ Time Frame: Baseline to 6 months ]

Measure Type	Secondary
Measure Name	Disease Activity Score (based on 28 joint count) (DAS28) at 6 months.
Measure Description	Change from baseline in the DAS28 composite score (a measure of RA symptoms including: joint swelling and tenderness; patient’s assessment of disease activity; and ESR) after 6 months’ treatment. A change of zero indicates no effect of treatment and a negative change of 1.2 indicates a clinically important improvement in symptoms. (The DAS scale runs from 0 to 10, with the higher scores indicating worse RA symptoms).
Time Frame	Baseline to 6 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD9056 50 mg	AZD9056 50 mg, oral tablets, once daily, double blinded
AZD9056 100 mg	AZD9056 100 mg, oral tablets, once daily, double blinded
AZD9056 200 mg	AZD9056 200 mg, oral tablets, once daily, double blinded
AZD9056 400 mg	AZD9056 400 mg, oral tablets, once daily, double blinded
Placebo	Placebo to AZD9056, oral tablets, once daily, double blinded
Etanercept	Etanercept 50 mg, subcutaneous injection, once weekly, open label

Measured Values

	AZD9056 50 mg	AZD9056 100 mg	AZD9056 200 mg	AZD9056 400 mg	Placebo	Etanercept
Number of Participants Analyzed [units:participants]	63	64	63	64	65	64
Disease Activity Score (based on 28 joint count) (DAS28) at 6 months. [units: Composite score] Mean (Standard Deviation)	-1.2 (1.27)	-1.4 (1.63)	-1.1 (1.47)	-1.4 (1.37)	-1 (1.24)	-2.3 (1.38)

No statistical analysis provided for Disease Activity Score (based on 28 joint count) (DAS28) at 6 months.

5. Secondary Outcome Measure: Health Assessment Questionnaire - Disability Index (HAQ-DI) at 6 months. [ Time Frame: Baseline to 6 months ]

Measure Type	Secondary
Measure Name	Health Assessment Questionnaire - Disability Index (HAQ-DI) at 6 months.
Measure Description	Change from baseline in HAQ-DI (a measure of patients assessment of physical function scored between zero and 3) after 6 months’ treatment, calculated as score at 6 months minus score at baseline. A change of zero indicates no effect of treatment and a negative change of 0.22 or greater indicates an improvement in symptoms. (The HAQ-DI scale runs from 0 to 3, with higher scores indicating greater disability).
Time Frame	Baseline to 6 months
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD9056 50 mg	AZD9056 50 mg, oral tablets, once daily, double blinded
AZD9056 100 mg	AZD9056 100 mg, oral tablets, once daily, double blinded
AZD9056 200 mg	AZD9056 200 mg, oral tablets, once daily, double blinded
AZD9056 400 mg	AZD9056 400 mg, oral tablets, once daily, double blinded
Placebo	Placebo to AZD9056, oral tablets, once daily, double blinded
Etanercept	Etanercept 50 mg, subcutaneous injection, once weekly, open label

Measured Values

	AZD9056 50 mg	AZD9056 100 mg	AZD9056 200 mg	AZD9056 400 mg	Placebo	Etanercept
Number of Participants Analyzed [units:participants]	63	64	63	64	65	64
Health Assessment Questionnaire - Disability Index (HAQ-DI) at 6 months. [units: Composite score] Mean (Standard Deviation)	-0.3 (0.57)	-0.3 (0.51)	-0.2 (0.5)	-0.3 (0.55)	-0.3 (0.46)	-0.6 (0.66)

No statistical analysis provided for Health Assessment Questionnaire - Disability Index (HAQ-DI) at 6 months.

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
AZD9056 50 mg	AZD9056 50 mg, oral tablets, once daily, double blinded
AZD9056 100 mg	AZD9056 100 mg, oral tablets, once daily, double blinded
AZD9056 200 mg	AZD9056 200 mg, oral tablets, once daily, double blinded
AZD9056 400 mg	AZD9056 400 mg, oral tablets, once daily, double blinded
Placebo	Placebo to AZD9056, oral tablets, once daily, double blinded
Etanercept	Etanercept 50 mg, subcutaneous injection, once weekly, open label

Serious Adverse Events

AZD9056 50 mg

AZD9056 100 mg

AZD9056 200 mg

AZD9056 400 mg

Placebo

Etanercept

Total, serious adverse events

# participants affected / at risk

2/63 (3.17%)

0/64 (0.00%)

1/63 (1.59%)

1/64 (1.56%)

1/65 (1.54%)

2/64 (3.13%)

Eye disorders

Visual Acuity Reduced¹,^†

# participants affected / at risk

0/63 (0.00%)

0/64 (0.00%)

1/63 (1.59%)

0/64 (0.00%)

0/65 (0.00%)

0/64 (0.00%)

Eye disorders

Non-Cardiac Chest Pain¹,^†

# participants affected / at risk

0/63 (0.00%)

0/64 (0.00%)

0/63 (0.00%)

1/64 (1.56%)

0/65 (0.00%)

0/64 (0.00%)

Injury, poisoning and procedural complications

Humerus Fracture¹,^†

# participants affected / at risk

0/63 (0.00%)

0/64 (0.00%)

0/63 (0.00%)

0/64 (0.00%)

0/65 (0.00%)

1/64 (1.56%)

Injury, poisoning and procedural complications

Tibia Fracture¹,^†

# participants affected / at risk

0/63 (0.00%)

0/64 (0.00%)

0/63 (0.00%)

0/64 (0.00%)

0/65 (0.00%)

1/64 (1.56%)

Musculoskeletal and connective tissue disorders

Joint Effusion¹,^†

# participants affected / at risk

0/63 (0.00%)

0/64 (0.00%)

0/63 (0.00%)

0/64 (0.00%)

1/65 (1.54%)

0/64 (0.00%)

Renal and urinary disorders

Renal Colic¹,^†

# participants affected / at risk

1/63 (1.59%)

0/64 (0.00%)

0/63 (0.00%)

0/64 (0.00%)

0/65 (0.00%)

0/64 (0.00%)

Renal and urinary disorders

Ureteral Polyp¹,^†

# participants affected / at risk

0/63 (0.00%)

0/64 (0.00%)

0/63 (0.00%)

0/64 (0.00%)

0/65 (0.00%)

1/64 (1.56%)

Reproductive system and breast disorders

Uterine Polyp¹,^†

# participants affected / at risk

1/63 (1.59%)

0/64 (0.00%)

0/63 (0.00%)

0/64 (0.00%)

0/65 (0.00%)

0/64 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 11.0
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
AZD9056 50 mg	AZD9056 50 mg, oral tablets, once daily, double blinded
AZD9056 100 mg	AZD9056 100 mg, oral tablets, once daily, double blinded
AZD9056 200 mg	AZD9056 200 mg, oral tablets, once daily, double blinded
AZD9056 400 mg	AZD9056 400 mg, oral tablets, once daily, double blinded
Placebo	Placebo to AZD9056, oral tablets, once daily, double blinded
Etanercept	Etanercept 50 mg, subcutaneous injection, once weekly, open label

Other Adverse Events

AZD9056 50 mg

AZD9056 100 mg

AZD9056 200 mg

AZD9056 400 mg

Placebo

Etanercept

Total, other (not including serious) adverse events

# participants affected / at risk

17/63 (26.98%)

24/64 (37.50%)

20/63 (31.75%)

29/64 (45.31%)

20/65 (30.77%)

11/64 (17.19%)

Gastrointestinal disorders

Nausea¹,^†

# participants affected / at risk

3/63 (4.76%)

7/64 (10.94%)

2/63 (3.17%)

7/64 (10.94%)

2/65 (3.08%)

1/64 (1.56%)

Gastrointestinal disorders

Abdominal Pain Upper¹,^†

# participants affected / at risk

2/63 (3.17%)

0/64 (0.00%)

5/63 (7.94%)

7/64 (10.94%)

3/65 (4.62%)

1/64 (1.56%)

Gastrointestinal disorders

Diarrhoea¹,^†

# participants affected / at risk

1/63 (1.59%)

0/64 (0.00%)

4/63 (6.35%)

6/64 (9.38%)

3/65 (4.62%)

0/64 (0.00%)

Infections and infestations

Bronchitis¹,^†

# participants affected / at risk

3/63 (4.76%)

4/64 (6.25%)

0/63 (0.00%)

2/64 (3.13%)

2/65 (3.08%)

1/64 (1.56%)

Musculoskeletal and connective tissue disorders

Rheumatoid Atheritis¹,^†

# participants affected / at risk

8/63 (12.70%)

6/64 (9.38%)

4/63 (6.35%)

6/64 (9.38%)

12/65 (18.46%)

2/64 (3.13%)

Musculoskeletal and connective tissue disorders

Back Pain¹,^†

# participants affected / at risk

1/63 (1.59%)

3/64 (4.69%)

4/63 (6.35%)

3/64 (4.69%)

1/65 (1.54%)

2/64 (3.13%)

Nervous system disorders

Headache¹,^†

# participants affected / at risk

3/63 (4.76%)

3/64 (4.69%)

7/63 (11.11%)

10/64 (15.63%)

4/65 (6.15%)

0/64 (0.00%)

Vascular disorders

Hypertension¹,^†

# participants affected / at risk

2/63 (3.17%)

4/64 (6.25%)

2/63 (3.17%)

3/64 (4.69%)

0/65 (0.00%)

6/64 (9.38%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 11.0
2	Term from vocabulary,

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description:

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Hybrid ACR, ACRn, individual ACR components, Erythrocyte sedimentation rate, Short-form-36, Rheumatoid Arthritis Quality of Life, Patient Assessment of Fatigue and DEXA X-ray scanning did not provide extra information so are not presented

Results Point of Contact

Name/Title:	Gerard Lynch
Organization:	AstraZeneca
E-mail:	[email protected]

Documents available

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=278&filename=CSR-D1520C00001.pdf
Download
CSR-D1520C00001.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

Omnicare Clinical

+49 2234 1852 0

Contact Backup

Omicare Clinical Research

+ 1 484 679-2400

Investigators

Principal Investigator

Edward Keystone

Mount Sinai Hospital

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=278&filename=CSR-D1520C00001.pdf

CSR-D1520C00001.pdf

Trial Results Summaries