986: Study to Investigate the Safety and Efficacy of Tregalizumab in Subjects (MTX-IR) With Active Rheumatoid Arthritis

• Sponsor: Biotest (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01999192
• Collaborator: AbbVie (Industry)
• Enrollment: 321
• Locations: 84
• Arms: 4
• Duration (Months): 21
• Patients Per Site: 3.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the efficacy and safety of three different Tregalizumab doses in combination with Methotrexate (MTX) in subjects who have active rheumatoid arthritis and an inadequate response to MTX alone.

The overall study duration is 24 weeks followed by a 24 week extension phase.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Tregalizumab; Drug: Placebo	Phase 2

Detailed Description

The planned clinical study 986 (TREAT 2b) is a 24-week study in patients with Active rheumatoid arthritis (RA) who have had an inadequate response to Methotrexate (MTX) alone. The main phase of this study is followed by a 24-week extension phase for subjects meeting the respective entry criteria. Patients will be randomized to one of three different Active treatment groups or Placebo. The primary efficacy variable is the proportion of subjects with an ACR20 response after 12 weeks of double blinded treatment with the study medication based on observed cases in the FAS.

At Week 12, all subjects who had a minimum improvement of at least 20% (from baseline) in their tender joint count (TJC) and swollen joint count (SJC) continued on the same treatment. Subjects who had not demonstrated an improvement of at least 20% of TJC and SJC were assessed as non-responders. Non-responders who received placebo were randomized to an active treatment dose in a blinded manner. Non-responders who received active treatment were rolled up to the next highest dose in a blinded manner, apart from those already on the highest dose. These subjects remained on the highest dose.

Study Design

• Study Type: Interventional
• Actual Enrollment: 321 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A 24-week Phase IIb, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Investigate the Efficacy and Safety of Tregalizumab (BT061) in Combination With Methotrexate in the Treatment of Subjects With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate Alone, Followed by a 24-week Extension Phase: T Cell REgulating Arthritis Trial 2b (TREAT 2b)
• Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Jul 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Level 1 Tregalizumab 25mg Tregalizumab s.c. weekly	Drug: Tregalizumab; humanized anti-CD4 mAb; Other Names: BT061
Experimental: Dose Level 2 Tregalizumab 100mg Tregalizumab s.c. weekly	Drug: Tregalizumab; humanized anti-CD4 mAb; Other Names: BT061
Experimental: Dose Level 3 Tregalizumab 200mg Tregalizumab s.c. weekly	Drug: Tregalizumab; humanized anti-CD4 mAb; Other Names: BT061
Placebo Comparator: Placebo Placebo s.c. weekly	Drug: Placebo; identical end formulation buffer

Outcome Measures

Primary Outcome Measures

1. The Proportion of Subjects Who Achieve an ACR20 at Week 12 Following Treatment With Tregalizumab + MTX Compared With Subjects Treated on Placebo + MTX [Week 12]

   The primary efficacy variable was the proportion of subjects with an ACR20 response after 12 weeks of double-blind treatment with the study medication. The analysis of the primary endpoint was performed using observed cases (OC) on the FAS.

Secondary Outcome Measures

1. Proportions of Subjects With an ACR 20 Response. [Week 24]

2. Proportions of Subjects With an ACR 50 & 70 Response. [Week 12 & Week 24]

3. Proportions of Subjects With an Disease Activity Score DAS28 <2.6 [Week 12 & Week 24]

4. Proportions of Subjects With Low Disease Activity DAS28 ≤3.2 [Week 12 & Week 24]

5. ACR Score [up to 48 weeks]

6. Simple Disease Activity Index [SDAI] ≤11 [week 12 & 24]

7. Clinical Disease Activity Index [CDAI] ≤10 [week 12 & 24]

8. DAS28 [up to 48 weeks]

9. EULAR Response [up to 48 weeks]

10. ACR Score Individual Components [up to 48 weeks]

11. DAS28 Score Individual Components [up to 48 weeks]

Other Outcome Measures

1. Pharmacokinetics [up to 48 weeks]

   AUC, Cmax, Tmax at baseline, and at Week (W) 2/Visit (V) 4, W4/V5, W8/V7, W12/V8, W24/V10, W3/V122, W48 (end of Treatment [EoT]/ early termination ET), and at follow-up (post EoT/post ET).

2. Evaluation of Safety, Patient Reported Outcomes & Blood Tests. [up to 48 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject demonstrates active RA according to the 1987 American College of Rheumatology (ACR) or 2010 ACR/European League Against Rheumatism (EULAR) classification criteria for RA with functional class I-III for ≥6 months.

2. Subject receives oral or parenteral MTX treatment for ≥12 weeks (overall), with an unchanged mode of application and stable MTX dose of ≥15 mg per week (or ≥12.5 mg per week in case of MTX intolerance), but no more than the highest locally approved dose for RA, for ≥8 weeks prior to baseline. The dose of MTX is expected to remain stable throughout the study and may be adjusted only for safety reasons. If applicable, the dose of folic acid must be unchanged for ≥8 weeks prior to baseline.

3. Subject meets the following two criteria at both screening and baseline: - At least 6 swollen joints at 28-joint assessment. - At least 6 tender joints at 28-joint assessment.

4. Subject has an erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) above the upper limit of normal (ULN) at screening. These tests may be repeated once during the screening period at the discretion of the investigator.

5. Subject is ≥18 and ≤75 years of age.

6. Subject has a body mass index ≥18 and ≤35 kg/m².

7. Subject receives treatment with corticosteroids ≤10 mg prednisone equivalent, stable for at least 4 weeks prior to baseline and during the study, if applicable.

8. Subject receives treatment with non-steroidal anti-inflammatory drugs (NSAIDs), stable for at least 2 weeks prior to baseline and during the study, if applicable.

9. Female subjects of childbearing potential: has both a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline.

10. Subject is judged to be in good general health as determined by the investigator based upon the results of medical history, laboratory profile, physical examination, chest X-ray (within 3 months before screening date is acceptable), and 12-lead electrocardiogram (ECG).

11. Subject has a cluster of differentiation 4 (CD4) cell count of > 400/µl at screening.

Exclusion Criteria:

1. Subject has previous exposure to any systemic biologic therapy (e.g., etanercept, adalimumab, rituximab, abatacept, tocilizumab), to Janus kinase (JAK) or spleen tyrosine kinase (SYK) inhibitors, or to Tregalizumab. Previous treatment with an anti-TNF agent is allowed only, if all of the following criteria apply: - treatment was stopped for reasons other than lack of efficacy or adverse events (AEs) - treatment was stopped at least 12 weeks or five half-lives of the compound prior to baseline (whichever is longer), and - the treatment period did not exceed 6 weeks.

2. Subject received treatment with conventional disease-modifying anti-rheumatic drugs (DMARDs) apart from MTX in the 12 weeks prior to baseline, and for DMARD leflunomide in the 24 weeks prior to baseline (except where specific leflunomide wash-out procedures were completed, following applicable guidelines).

3. Subject has been treated with intra-articular or parenteral administration of corticosteroids in the 4 weeks prior to baseline. Inhaled corticosteroids for stable medical conditions are allowed.

4. Subject has undergone joint surgery in the 12 weeks prior to baseline (at joints to be assessed within the study) or has undergone major surgery (e.g., abdominal surgery) in the 8 weeks prior to baseline.

5. Subject has a history of acute inflammatory joint disease of an origin other than RA or subject has any other rheumatic disease other than RA (e.g., mixed connective tissue disease, seronegative spondylarthropathy, psoriatic arthritis, Reiter's syndrome, fibromyalgia, systemic lupus erythematosus or any arthritis with onset prior to age 17 years). However, subjects may have secondary Sjögren's syndrome.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Study Site 07	Paradise Valley	Arizona	United States	85253
2	Study Site 01	Springfield	Illinois	United States	62704
3	Study Site 03	Lincoln	Nebraska	United States	68516
4	Study Site 02	Clifton	New Jersey	United States	07012
5	Study Site 04	North Charleston	South Carolina	United States	29406
6	Study Site 05	Jackson	Tennessee	United States	38305
7	Study Site 09	Houston	Texas	United States	77004
8	Study Site 10	Katy	Texas	United States	77450
9	Study Site 01	Plovdiv		Bulgaria
10	Study Site 06	Plovdiv		Bulgaria
11	Study Site 02	Sofia		Bulgaria
12	Study Site 04	Sofia		Bulgaria
13	Study Site 07	Sofia		Bulgaria
14	Study Site 05	Stara Zagora		Bulgaria
15	Study Site 03	Varna		Bulgaria
16	Study Site 02	Rimouski	Quebec	Canada
17	Study Site 01	St-Jérôme	Quebec	Canada
18	Study Site 03	Bruntal		Czechia
19	Study Site 05	Ostrava		Czechia
20	Study Site 01	Praha		Czechia
21	Study Site 04	Praha		Czechia
22	Study Site 08	Praha		Czechia
23	Study Site 09	Praha		Czechia
24	Study Site 02	Uherske Hradiste		Czechia
25	Study Site 07	Uherske Hradiste		Czechia
26	Study Site 06	Zlin		Czechia
27	Study Site 01	Tallinn		Estonia
28	Study Site 03	Berlin		Germany
29	Study Site 04	Frankfurt		Germany
30	Study Site 06	Muenchen		Germany
31	Study Site 02	Ratingen		Germany
32	Study Site 01	Zerbst		Germany
33	Study Site 03	Balatonfüred		Hungary
34	Study Site 02	Budapest		Hungary
35	Study Site 04	Budapest		Hungary
36	Study Site 05	Budapest		Hungary
37	Study Site 06	Gyula		Hungary
38	Study Site 01	Veszprem		Hungary
39	Study Site 01	Kaunas		Lithuania
40	Study Site 02	Vilnus		Lithuania
41	Study Site 05	Mexico	Distrito Federal	Mexico
42	Study Site 08	Mexico	Distrito Federal	Mexico
43	Study Site 06	Leon	Guanajuato	Mexico
44	Study Site 02	Chihuahua		Mexico
45	Study Site 03	Distrito Federal		Mexico
46	Study Site 08	Bialystok		Poland
47	Study Site 05	Bydgoszcz		Poland
48	Study Site 10	Elblag		Poland
49	Study Site 04	Gdynia		Poland
50	Study Site 02	Katowice		Poland
51	Study Site 03	Krakow		Poland
52	Study Site 06	Krakow		Poland
53	Study Site 09	Poznan		Poland
54	Study Site 01	Warszawa		Poland
55	Study Site 07	Warszawa		Poland
56	Study Site 08	Kemerovo		Russian Federation
57	Study Site 11	Kemerovo		Russian Federation
58	Study Site 04	Kursk		Russian Federation
59	Study Site 03	Moscow		Russian Federation
60	Study Site 07	Moscow		Russian Federation
61	Study Site 10	Moscow		Russian Federation
62	Study Site 05	Omsk		Russian Federation
63	Study Site 09	Saratov		Russian Federation
64	Study Site 06	Smolensk		Russian Federation
65	Study Site 01	Tomsk		Russian Federation
66	Study Site 02	Yaroslavl		Russian Federation
67	Study Site 01	Belgrade		Serbia
68	Study Site 02	Belgrade		Serbia
69	Study Site 04	Belgrade		Serbia
70	Study Site 03	Niska Banja		Serbia
71	Study Site 03	Bratislava		Slovakia
72	Study Site 04	Kosice - Saca		Slovakia
73	Study Site 05	Lucenec		Slovakia
74	Study Site 02	Povazska Bystrica		Slovakia
75	Study Site 01	Rimavska Sobota		Slovakia
76	Study Site 08	Donetsk		Ukraine
77	Study Site 01	Kharkiv		Ukraine
78	Study Site 02	Kharkiv		Ukraine
79	Study Site 03	Kyiv		Ukraine
80	Study Site 04	Kyiv		Ukraine
81	Study Site 05	Vinnytsia		Ukraine
82	Study Site 06	Vinnytsia		Ukraine
83	Study Site 07	Vinnytsia		Ukraine
84	Study Site 09	Zaporizhzhia		Ukraine

Sponsors and Collaborators

• Biotest
• AbbVie

Investigators

• Principal Investigator: Ronald van Vollenhoven, Prof. MD, Karolinska Universitetssjukhuset, Solna

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Biotest
• ClinicalTrials.gov Identifier: NCT01999192
• Other Study ID Numbers: 986_TREAT 2b; 2013-000114-38; BT986
• First Posted: Dec 3, 2013
• Last Update Posted: Aug 24, 2017
• Last Verified: Jul 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Biotest: inadequate response to MTX; Methotrexate; rheumatoid Arthritis; Phase 2b
• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid

Study Results

Participant Flow

Arm/Group Title	Dose Level 1 Tregalizumab	Dose Level 2 Tregalizumab	Dose Level 3 Tregalizumab	Placebo
Arm/Group Description	25mg Tregalizumab s.c. weekly	100mg Tregalizumab s.c. weekly	200mg Tregalizumab s.c. weekly	Placebo s.c. weekly
Period Title: Main Phase I
STARTED	83	80	78	80
COMPLETED	72	70	70	72
NOT COMPLETED	11	10	8	8
Period Title: Main Phase I
STARTED	64	75	98	44
COMPLETED	55	66	76	43
NOT COMPLETED	9	9	22	1
Period Title: Main Phase I
STARTED	54	56	68	0
COMPLETED	41	38	44	0
NOT COMPLETED	13	18	24	0

Baseline Characteristics

Arm/Group Title	Dose Level 1 Tregalizumab	Dose Level 2 Tregalizumab	Dose Level 3 Tregalizumab	Placebo	Total
Arm/Group Description	25mg Tregalizumab s.c. weekly	100mg Tregalizumab s.c. weekly	200mg Tregalizumab s.c. weekly	Placebo s.c. weekly	Total of all reporting groups
Overall Participants	80	78	76	79	313
Age, Customized (years) [Number]
0-<40 years	9	19	12	10	50
40-<=65 years	62	56	56	57	231
>65 years	9	3	8	12	32
Sex: Female, Male (Count of Participants)
Female	71 88.8%	68 87.2%	58 76.3%	66 83.5%	263 84%
Male	9 11.3%	10 12.8%	18 23.7%	13 16.5%	50 16%

Outcome Measures

1. Primary Outcome

Title	The Proportion of Subjects Who Achieve an ACR20 at Week 12 Following Treatment With Tregalizumab + MTX Compared With Subjects Treated on Placebo + MTX
Description	The primary efficacy variable was the proportion of subjects with an ACR20 response after 12 weeks of double-blind treatment with the study medication. The analysis of the primary endpoint was performed using observed cases (OC) on the FAS.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The analysis of the primary endpoint was performed using observed cases (OC) on the FAS. Full analysis set (FAS): All subjects entered into the study who received at least one dose of study medication and have at least one post-baseline assessment.

Arm/Group Title	Dose Level 1 Tregalizumab	Dose Level 2 Tregalizumab	Dose Level 3 Tregalizumab	Placebo
Arm/Group Description	25mg Tregalizumab s.c. weekly	100mg Tregalizumab s.c. weekly	200mg Tregalizumab s.c. weekly	Placebo s.c. weekly
Measure Participants	71	66	70	71
Number [percentage of Subjects]	42.3	47.0	44.3	35.2

2. Secondary Outcome

Title	Proportions of Subjects With an ACR 20 Response.
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Proportions of Subjects With an ACR 50 & 70 Response.
Time Frame	Week 12 & Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Proportions of Subjects With an Disease Activity Score DAS28 <2.6
Time Frame	Week 12 & Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Proportions of Subjects With Low Disease Activity DAS28 ≤3.2
Time Frame	Week 12 & Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	ACR Score
Time Frame	up to 48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Simple Disease Activity Index [SDAI] ≤11
Time Frame	week 12 & 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Secondary Outcome

Title	Clinical Disease Activity Index [CDAI] ≤10
Time Frame	week 12 & 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Secondary Outcome

Title	DAS28
Time Frame	up to 48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Secondary Outcome

Title	EULAR Response
Time Frame	up to 48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Secondary Outcome

Title	ACR Score Individual Components
Time Frame	up to 48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Secondary Outcome

Title	DAS28 Score Individual Components
Time Frame	up to 48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

13. Other Pre-specified Outcome

Title	Pharmacokinetics
Description	AUC, Cmax, Tmax at baseline, and at Week (W) 2/Visit (V) 4, W4/V5, W8/V7, W12/V8, W24/V10, W3/V122, W48 (end of Treatment [EoT]/ early termination ET), and at follow-up (post EoT/post ET).
Time Frame	up to 48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Other Pre-specified Outcome

Title	Evaluation of Safety, Patient Reported Outcomes & Blood Tests.
Time Frame	up to 48 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	through study completion, up to 1 year
Adverse Event Reporting Description	All adverse events have been matched in accordance with the dosing under which they occurred. This resulted in a higher number of subjects at risk, because some subjects received two dosages. Patients who responded at week 12 continued the same treatment for 12 weeks and non-responders at week 12 were escalated to the next higher dose level or re-randomized to active treatment (placebo patients). After 24 weeks, placebo patients were switched to active treatment during the Extension Phase.
Arm/Group Title	25mg Dose Level 1 Tregalizumab		100mg Dose Level 2 Tregalizumab		200mg Dose Level 3 Tregalizumab		Placebo
Arm/Group Description	Dose Level 1 Tregalizumab (25mg)		Dose Level 2 Tregalizumab (100mg)		Dose Level 3 Tregalizumab (200mg)		Placebo -
All Cause Mortality
	25mg Dose Level 1 Tregalizumab		100mg Dose Level 2 Tregalizumab		200mg Dose Level 3 Tregalizumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	25mg Dose Level 1 Tregalizumab		100mg Dose Level 2 Tregalizumab		200mg Dose Level 3 Tregalizumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/105 (2.9%)		1/117 (0.9%)		7/122 (5.7%)		1/80 (1.3%)
Cardiac disorders
Acute Coronary Syndrome	1/105 (1%)	1	0/117 (0%)	0	0/122 (0%)	0	0/80 (0%)	0
Gastrointestinal disorders
Abdominal Hernia	0/105 (0%)	0	0/117 (0%)	0	1/122 (0.8%)	1	0/80 (0%)	0
Colitis	1/105 (1%)	1	0/117 (0%)	0	0/122 (0%)	0	0/80 (0%)	0
General disorders
Death	0/105 (0%)	0	0/117 (0%)	0	1/122 (0.8%)	1	0/80 (0%)	0
Infections and infestations
Gangrene	0/105 (0%)	0	0/117 (0%)	0	1/122 (0.8%)	1	0/80 (0%)	0
Peritonitis	1/105 (1%)	1	0/117 (0%)	0	0/122 (0%)	0	0/80 (0%)	0
Injury, poisoning and procedural complications
Multiple Injuries	0/105 (0%)	0	1/117 (0.9%)	1	0/122 (0%)	0	0/80 (0%)	0
Road Traffic Accident	0/105 (0%)	0	1/117 (0.9%)	1	0/122 (0%)	0	0/80 (0%)	0
Frostbite	0/105 (0%)	0	0/117 (0%)	0	1/122 (0.8%)	1	0/80 (0%)	0
Investigations
Flavivirus Test Positive	0/105 (0%)	0	0/117 (0%)	0	0/122 (0%)	0	1/80 (1.3%)	1
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/105 (1%)	1	0/117 (0%)	0	0/122 (0%)	0	0/80 (0%)	0
Nervous system disorders
Multiple Sclerosis	0/105 (0%)	0	0/117 (0%)	0	0/122 (0%)	0	1/80 (1.3%)	1
Cerebral Haemorrhage	0/105 (0%)	0	0/117 (0%)	0	1/122 (0.8%)	1	0/80 (0%)	0
Generalised Tonic-Clonic Seizure	0/105 (0%)	0	0/117 (0%)	0	1/122 (0.8%)	1	0/80 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/105 (0%)	0	0/117 (0%)	0	1/122 (0.8%)	1	0/80 (0%)	0
Skin and subcutaneous tissue disorders
Lichen Planus	0/105 (0%)	0	0/117 (0%)	0	1/122 (0.8%)	1	0/80 (0%)	0
Vascular disorders
Shock Haemorrhagic	0/105 (0%)	0	1/117 (0.9%)	1	0/122 (0%)	0	0/80 (0%)	0
Other (Not Including Serious) Adverse Events
	25mg Dose Level 1 Tregalizumab		100mg Dose Level 2 Tregalizumab		200mg Dose Level 3 Tregalizumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/105 (13.3%)		16/117 (13.7%)		15/122 (12.3%)		9/80 (11.3%)
Infections and infestations
Nasopharyngitis	7/105 (6.7%)	9	6/117 (5.1%)	7	7/122 (5.7%)	10	4/80 (5%)	4
Musculoskeletal and connective tissue disorders
Rheumatoid Arthritis	5/105 (4.8%)	5	6/117 (5.1%)	6	5/122 (4.1%)	5	2/80 (2.5%)	3
Nervous system disorders
Headache	3/105 (2.9%)	4	6/117 (5.1%)	9	6/122 (4.9%)	6	3/80 (3.8%)	3

Limitations/Caveats

Due to the lack of efficacy the Extension Phase of the study was terminated early.

More Information

Certain Agreements

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

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.