Study in Rheumatoid Arthritis for Subjects Who Completed Preceding Study M13-390 With Adalimumab

• Sponsor: AbbVie (prior sponsor, Abbott) (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01752855
• Collaborator: (none)
• Enrollment: 88
• Locations: 20
• Arm: 1
• Duration (Months): 10
• Patients Per Site: 4.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

A Phase 2b, open-label extension (OLE) study in rheumatoid arthritis (RA) patients designed to collect long-term safety, tolerability, efficacy, and immunogenicity data of the proposed new adalimumab formulation.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Biological: New formulation adalimumab	Phase 2

Detailed Description

All participants who completed Study NCT01712178 had an opportunity to enroll into the study and to receive the new adalimumab formulation at a dose of 40 mg every other week (eow) for an additional 24 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 88 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2b, Multicenter, Open-Label Study in Rheumatoid Arthritis Subjects Who Completed Preceding Study M13-390 With Adalimumab
• Study Start Date: Dec 1, 2012
• Actual Primary Completion Date: Oct 1, 2013
• Actual Study Completion Date: Oct 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: New formulation of adalimumab 40 mg every other week New formulation adalimumab 40 mg every other week	Biological: New formulation adalimumab; New formulation adalimumab 40 mg every other week; Other Names: Humira

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in Disease Activity Score 28 (DAS28) at Weeks 36 and 48 [Baseline (Study NCT01712178 Week 0 Visit), Weeks 36 and 48]

   The Disease Activity Score (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission.

2. Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Weeks 36 and 48 [Baseline (Study NCT01712178 Week 0 Visit), Weeks 36 and 48]

   American College of Rheumatology 20% (ACR20) response. A participant is a responder if the following 3 criteria for improvement from baseline are met: ≥ 20% improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Disability Index of the Health Assessment CRP (Acute phase reactant (Erythrocyte sedimentation rate/C-reactive protein))

3. Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Weeks 36 and 48 [Baseline (Study NCT01712178 Week 0 Visit), Weeks 36 and 48]

   American College of Rheumatology 50% (ACR50) response. A participant is a responder if the following 3 criteria for improvement from baseline are met: ≥ 50% improvement in tender joint count; ≥ 50% improvement in swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Disability Index of the Health Assessment CRP (Acute phase reactant (Erythrocyte sedimentation rate/C-reactive protein))

4. Mean Change From Baseline in Health Assessment Questionnaire (HAQ-DI) at Weeks 36 and 48 [Baseline (Study NCT01712178 Week 0 Visit), Weeks 36 and 48]

   The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. The minimal clinically important difference (MCID) defined for the HAQ-DI is 0.22. HAQ remission indicating normal physical function is defined by HAQ-DI < 0.5.

Secondary Outcome Measures

1. Percentage of Participants Positive for Anti-adalimumab Antibody [Week 24 through Week 48]

   Percentage of participants with anti-adalimumab antibody

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject has completed the preceding Study M13-390 for rheumatoid arthritis and has not developed any discontinuation criteria from that study.

2. If female, subject is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy and/or hysterectomy) or is of childbearing potential and is practicing an approved method of birth control throughout the study and for 150 days after last dose of study drug. Examples of approved methods of birth control include the following (see local informed consent for more detail):

• Condoms, sponge, foams, jellies, diaphragm or intrauterine device (IUD);

• Hormonal contraceptives for 90 days prior to study drug administration;

• A vasectomized partner.

1. Subjects must be able and willing to self-administer subcutaneous (SC) injections or have a qualified person available to administer SC injections.

2. Subject is judged to be in good general health as determined by the Principal Investigator based upon the results of medical history, physical examination, laboratory profile performed at Baseline.

3. Subjects must be able and willing to provide written informed consent and to comply with the requirements of this study protocol.

Exclusion Criteria:

1. Ongoing infections at Week 0 that have NOT been successfully treated. Subjects with ongoing infections undergoing treatment may be enrolled BUT NOT dosed until the infection has been successfully treated.

2. Subject currently uses or plans to use anti-retroviral therapy at any time during the study.

3. Subject plans to use any live vaccine during the study.

4. Positive pregnancy test at Baseline (Week 0).

5. Subject is considered by the investigator, for any reason, to be an unsuitable candidate for the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site Reference ID/Investigator# 92113	Mesa	Arizona	United States	85202
2	Site Reference ID/Investigator# 92118	Hemet	California	United States	92543
3	Site Reference ID/Investigator# 92117	Wichita	Kansas	United States	67203
4	Site Reference ID/Investigator# 92115	Clifton	New Jersey	United States	07012
5	Site Reference ID/Investigator# 92116	Philadelphia	Pennsylvania	United States	19152
6	Site Reference ID/Investigator# 92114	Charleston	South Carolina	United States	29406
7	Site Reference ID/Investigator# 92053	Brussels		Belgium	1200
8	Site Reference ID/Investigator# 92054	Liege		Belgium	4000
9	Site Reference ID/Investigator# 91954	Brno		Czech Republic	638 00
10	Site Reference ID/Investigator# 91955	Prague 2		Czech Republic	128 50
11	Site Reference ID/Investigator# 91953	Uherske Hradiste		Czech Republic	686 01
12	Site Reference ID/Investigator# 91956	Zlin		Czech Republic	760 01
13	Site Reference ID/Investigator# 92073	Ratingen		Germany	40882
14	Site Reference ID/Investigator# 92074	Vega Baja		Puerto Rico	00693
15	Site Reference ID/Investigator# 92093	Bucharest		Romania	020475
16	Site Reference ID/Investigator# 92095	Cluj-Napoca		Romania	400006
17	Site Reference ID/Investigator# 92094	Ploiesti		Romania	100337
18	Site Reference ID/Investigator# 92096	Banska Bystrica		Slovakia	97405
19	Site Reference ID/Investigator# 92097	Senica		Slovakia	905 01
20	Site Reference ID/Investigator# 92098	Zilina		Slovakia	010 01

Sponsors and Collaborators

• AbbVie (prior sponsor, Abbott)

Investigators

• Study Director: Andy Payne, PhD, AbbVie

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• This clinical study may be evaluating a usage that is not currently FDA-approved. Please see US Prescribing Information for approved uses.

Publications

None provided.

• Responsible Party: AbbVie (prior sponsor, Abbott)
• ClinicalTrials.gov Identifier: NCT01752855
• Other Study ID Numbers: M13-692; 2012-003881-42
• First Posted: Dec 19, 2012
• Last Update Posted: Oct 29, 2014
• Last Verified: Oct 1, 2014

• Keywords provided by AbbVie (prior sponsor, Abbott): Rheumatoid Arthritis
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Adalimumab

Study Results

Participant Flow

Arm/Group Title	New Formulation for 48 Weeks	Current Formulation for 24 Weeks, New Formulation for 24 Weeks
Arm/Group Description	New formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week	Current formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week
Period Title: Overall Study
STARTED	44	44
COMPLETED	43	40
NOT COMPLETED	1	4

Baseline Characteristics

Arm/Group Title	New Formulation for 48 Weeks	Current Formulation for 24 Weeks, New Formulation for 24 Weeks	Total
Arm/Group Description	New formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week	Current formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week	Total of all reporting groups
Overall Participants	44	44	88
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.7 (10.8)	52.0 (12.0)	53.9 (11.5)
Sex: Female, Male (Count of Participants)
Female	37 84.1%	37 84.1%	74 84.1%
Male	7 15.9%	7 15.9%	14 15.9%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in Disease Activity Score 28 (DAS28) at Weeks 36 and 48
Description	The Disease Activity Score (DAS28) is a validated index of rheumatoid arthritis disease activity. Twenty-eight tender joint counts, 28 swollen joint counts, C-reactive protein, and general health are included in the DAS28 score. Scores on the DAS28 range from 0 to 10. A DAS28 score >5.1 indicates high disease activity, a DAS28 score <3.2 indicates low disease activity, and a DAS28 score <2.6 indicates clinical remission.
Time Frame	Baseline (Study NCT01712178 Week 0 Visit), Weeks 36 and 48

Outcome Measure Data

Analysis Population Description

All available data were included. If a participant did not have a value for a given time of evaluation, but did have a value at times previous to this after the study drug treatment began, the last available value was used to replace the missing value.

Arm/Group Title	New Formulation for 48 Weeks	Current Formulation for 24 Weeks, New Formulation for 24 Weeks
Arm/Group Description	New formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week	Current formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week
Measure Participants	44	44
Week 36	-2.4 (1.17)	-2.2 (1.05)
Week 48	-2.4 (1.29)	-2.2 (1.28)

2. Primary Outcome

Title	Percentage of Participants With an American College of Rheumatology (ACR) 20 Response at Weeks 36 and 48
Description	American College of Rheumatology 20% (ACR20) response. A participant is a responder if the following 3 criteria for improvement from baseline are met: ≥ 20% improvement in tender joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Disability Index of the Health Assessment CRP (Acute phase reactant (Erythrocyte sedimentation rate/C-reactive protein))
Time Frame	Baseline (Study NCT01712178 Week 0 Visit), Weeks 36 and 48

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.

Arm/Group Title	New Formulation for 48 Weeks	Current Formulation for 24 Weeks, New Formulation for 24 Weeks
Arm/Group Description	New formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week	Current formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week
Measure Participants	44	44
Week 36	72.7 165.2%	76.7 174.3%
Week 48	74.4 169.1%	80.0 181.8%

3. Primary Outcome

Title	Percentage of Participants With an American College of Rheumatology (ACR) 50 Response at Weeks 36 and 48
Description	American College of Rheumatology 50% (ACR50) response. A participant is a responder if the following 3 criteria for improvement from baseline are met: ≥ 50% improvement in tender joint count; ≥ 50% improvement in swollen joint count; and ≥ 50% improvement in at least 3 of the 5 following parameters: Physician global assessment of disease activity Patient global assessment of disease activity Patient assessment of pain Disability Index of the Health Assessment CRP (Acute phase reactant (Erythrocyte sedimentation rate/C-reactive protein))
Time Frame	Baseline (Study NCT01712178 Week 0 Visit), Weeks 36 and 48

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.

Arm/Group Title	New Formulation for 48 Weeks	Current Formulation for 24 Weeks, New Formulation for 24 Weeks
Arm/Group Description	New formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week	Current formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week
Measure Participants	44	44
Week 36	50.0 113.6%	51.2 116.4%
Week 48	53.5 121.6%	57.5 130.7%

4. Primary Outcome

Title	Mean Change From Baseline in Health Assessment Questionnaire (HAQ-DI) at Weeks 36 and 48
Description	The Health Assessment Questionnaire - Disability Index (HAQ-DI) is a patient-reported questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to eight domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and daily activities. Participants assessed their ability to do each task over the past week using the following response categories: without any difficulty (0); with some difficulty (1); with much difficulty (2); and unable to do (3). Scores on each task were summed and averaged to provide an overall score ranging from 0 to 3, where zero represents no disability and three very severe, high-dependency disability. The minimal clinically important difference (MCID) defined for the HAQ-DI is 0.22. HAQ remission indicating normal physical function is defined by HAQ-DI < 0.5.
Time Frame	Baseline (Study NCT01712178 Week 0 Visit), Weeks 36 and 48

Outcome Measure Data

Analysis Population Description

Data from participants receiving the new formulation of adalimumab in Study NCT01712178 were analyzed for 44 and 43 participants, respectively, at weeks 36 and 48. Data for the participants receiving the current formulation of adalimumab in Study NCT01712178 were analyzed for 43 participants at week 36 and 40 participants at week 48.

Arm/Group Title	New Formulation for 48 Weeks	Current Formulation for 24 Weeks, New Formulation for 24 Weeks
Arm/Group Description	New formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week	Current formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week
Measure Participants	44	43
Week 36	-0.5 (0.60)	-0.5 (0.69)
Week 48	-0.5 (0.57)	-0.5 (0.58)

5. Secondary Outcome

Title	Percentage of Participants Positive for Anti-adalimumab Antibody
Description	Percentage of participants with anti-adalimumab antibody
Time Frame	Week 24 through Week 48

Outcome Measure Data

Analysis Population Description

All participants who received at least one dose of study drug.

Arm/Group Title	New Formulation for 48 Weeks	Current Formulation for 24 Weeks, New Formulation for 24 Weeks
Arm/Group Description	New formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week	Current formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week
Measure Participants	44	44
Number [percentage of participants]	13.6 30.9%	18.2 41.4%

Adverse Events

Time Frame	Adverse events were collected from the time of study drug administration until 70 days following the last dose, approximately 58 weeks. Serious adverse events were collected from the time the participant signed the informed consent.
Arm/Group Title	New Formulation for 48 Weeks		Current Formulation for 24 Weeks, New Formulation for 24 Weeks
Arm/Group Description	New formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week.		Current formulation of adalimumab 40 mg every other week for 24 weeks in Study NCT01712178, followed by 24 weeks of treatment with the new formulation of adalimumab 40 mg every other week
All Cause Mortality
	New Formulation for 48 Weeks		Current Formulation for 24 Weeks, New Formulation for 24 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	New Formulation for 48 Weeks		Current Formulation for 24 Weeks, New Formulation for 24 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/44 (4.5%)		1/44 (2.3%)
Blood and lymphatic system disorders
IRON DEFICIENCY ANAEMIA	1/44 (2.3%)		0/44 (0%)
Cardiac disorders
ATRIAL FIBRILLATION	1/44 (2.3%)		0/44 (0%)
Musculoskeletal and connective tissue disorders
OSTEOARTHRITIS	1/44 (2.3%)		1/44 (2.3%)
Other (Not Including Serious) Adverse Events
	New Formulation for 48 Weeks		Current Formulation for 24 Weeks, New Formulation for 24 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/44 (40.9%)		19/44 (43.2%)
Gastrointestinal disorders
DYSPEPSIA	3/44 (6.8%)		3/44 (6.8%)
Infections and infestations
CYSTITIS	4/44 (9.1%)		2/44 (4.5%)
NASOPHARYNGITIS	6/44 (13.6%)		7/44 (15.9%)
ORAL HERPES	3/44 (6.8%)		2/44 (4.5%)
UPPER RESPIRATORY TRACT INFECTION	4/44 (9.1%)		4/44 (9.1%)
Investigations
ASPARTATE AMINOTRANSFERASE INCREASED	2/44 (4.5%)		3/44 (6.8%)
Musculoskeletal and connective tissue disorders
BACK PAIN	0/44 (0%)		3/44 (6.8%)
RHEUMATOID ARTHRITIS	3/44 (6.8%)		4/44 (9.1%)
Nervous system disorders
HEADACHE	3/44 (6.8%)		3/44 (6.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.