A Study to Evaluate the Efficacy and Safety of MLTA3698A in Combination With a Disease-Modifying Anti-Rheumatic Drug (DMARD) Compared With Adalimumab in Combination With a DMARD in Patients With Active Rheumatoid Arthritis

Sponsor

Genentech, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01225393

Collaborator

(none)

211

Enrollment

Locations

Arms

3.1

Patients Per Site

Study Details

Study Description

Brief Summary

This is a Phase II, randomized, double-blind, placebo-controlled, parallel-group, multicenter study enrolling patients with active rheumatoid arthritis (RA).

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: MLTA3698A Drug: adalimumab Drug: leflunomide Drug: methotrexate Drug: placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

211 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Phase II, Randomized, Double-Blind, Parallel-Group Study to Evaluate the Efficacy and Safety of MLTA3698A in Combination With a Disease-Modifying Anti-Rheumatic Drug (DMARD) Compared With Adalimumab in Combination With a DMARD in Patient With Active Rheumatoid Arthritis

Study Start Date :

Nov 1, 2010

Actual Primary Completion Date :

Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A	Drug: MLTA3698A Subcutaneous repeating dose Drug: leflunomide Stable dose if not on methotrexate Drug: methotrexate Stable dose if not on leflunomide
Active Comparator: B	Drug: adalimumab Subcutaneous repeating dose Drug: leflunomide Stable dose if not on methotrexate Drug: methotrexate Stable dose if not on leflunomide Drug: placebo Subcutaneous repeating dose
Placebo Comparator: C	Drug: leflunomide Stable dose if not on methotrexate Drug: methotrexate Stable dose if not on leflunomide Drug: placebo Subcutaneous repeating dose

Arm

Intervention/Treatment

Experimental: A

Drug: MLTA3698A

Subcutaneous repeating dose

Drug: leflunomide

Stable dose if not on methotrexate

Drug: methotrexate

Stable dose if not on leflunomide

Active Comparator: B

Drug: adalimumab

Subcutaneous repeating dose

Drug: leflunomide

Stable dose if not on methotrexate

Drug: methotrexate

Stable dose if not on leflunomide

Drug: placebo

Subcutaneous repeating dose

Placebo Comparator: C

Drug: leflunomide

Stable dose if not on methotrexate

Drug: methotrexate

Stable dose if not on leflunomide

Drug: placebo

Subcutaneous repeating dose

Outcome Measures

Primary Outcome Measures

Baseline change in disease activity, assessed as the Disease Activity Score (DAS28) and erythrocyte sedimentation rate, or DAS28-(4)-ESR [Day 85]
Incidence and severity of adverse events and clinical laboratory abnormalities as a measure of safety and tolerability of MLTA3698A [Length of study (through Day 85)]

Secondary Outcome Measures

ACR20 response rate (the proportion of patients in each treatment group meeting the American College of Rheumatology 20% responder criteria [ACR20] for their average response ) [Day 85]
ACR50 response rate (the proportion of patients in each treatment group meeting the American College of Rheumatology 50% responder criteria [ACR50] for their average response ) [Day 85]
ACR70 response rate (the proportion of patients in each treatment group meeting the American College of Rheumatology 70% responder criteria [ACR70] for their average response) [Day 85]
Tender joint count [Day 85]
Swollen joint count [Day 85]
Investigator Global Assessment of Disease Activity [Day 85]
Patient Global Assessment of Pain and Disease Activity [Day 85]
Health Assessment Questionnaire Disability Index [Day 85]
Patient's Global Health or Short Form Health Survey (SF-36) [Day 85]
European League Against Rheumatism response rate [Day 85]
Serum C-reactive protein levels [Day 85]
Erythrocyte sedimentation rate [Day 85]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of RA according to the 1987 revised ACR Criteria for the Classification of RA for at least 6 months prior to screening
Positive for rheumatoid factor or anti-cyclic citrullinated peptide (CCP) antibody, or both
Active disease, defined as: CRP >= 1.0 mg/dL; swollen joint count >= 6 (66 joint count); tender joint count >= 6 (68 joint count)
Previous inadequate clinical response to at least one disease-modifying anti-rheumatic drug (DMARD) consisting of either methotrexate (MTX) or leflunomide (LFU)
For patients currently receiving corticosteroids: Treatment at a stable dose during last 4 weeks prior to screening
For patients currently receiving non-steroidal anti-inflammatory drugs (NSAIDs): Treatment at a stable dose during last 4 weeks prior to screening
For patients currently receiving sulfasalazine or anti-malarials: Treatment initiated and continued for at least the last 6 months prior to screening and on a stable dose
For patients of reproductive potential (males and females): Willing to use a highly effective birth control method for the duration of the study according to local guidelines

Exclusion Criteria:

Pregnant, planning to become pregnant during the study, or breastfeeding
Clinically significant abnormal laboratory values or abnormal ECG or vital signs
History of anaphylactic reactions
Rheumatic autoimmune disease other than RA, or significant systemic involvement secondary to RA (including but not limited to vasculitis, pulmonary fibrosis, or Felty's syndrome), however patients with secondary Sjogren's syndrome are eligible for the study
History of or current inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthritis, Lyme disease) or other systemic autoimmune disorder (e.g., systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease, or other overlap syndrome)
Current or recent (within 4 weeks prior to screening) infection, including signs, symptoms or serology of any infection, including HIV, hepatitis B or C, tuberculosis
Administration of a live, attenuated vaccine within 1 month before dosing or anticipation that such a live attenuated vaccine will be required during the study
Previous treatment with anti-TNF biologics or other biologic agents, including anti-CD20-directed therapy (e.g. rituximab), anti-IL6-directed therapy (e.g. tocilizumab), or T cell-directed therapy (e.g. abatacept)

Contacts and Locations

Locations

	City	State	Country	Postal Code
1	Anniston	Alabama	United States	36207
2	Birmingham	Alabama	United States	35216
3	Peoria	Arizona	United States	85381
4	Los Angeles	California	United States	90033
5	Upland	California	United States	91786
6	Ormond Beach	Florida	United States	32174
7	Lexington	Kentucky	United States	40515
8	Kalamazoo	Michigan	United States	49009
9	Flowood	Mississippi	United States	39232
10	Reno	Nevada	United States	89502
11	Charleston	South Carolina	United States	29406
12	San Antonio	Texas	United States	78217
13	Chesapeake	Virginia	United States	23320
14	Clarksburg	West Virginia	United States	26301
15	Sofia		Bulgaria	1233
16	Sofia		Bulgaria	1407
17	Sofia		Bulgaria	1505
18	Santiago		Chile	00000
19	Santiago		Chile	7501126
20	Santiago		Chile	7510186
21	Bad Nauheim		Germany	61231
22	Berlin		Germany	14059
23	Erfurt		Germany	99096
24	Freiburg		Germany	79106
25	Herne		Germany	44649
26	Kiel		Germany	24105
27	Köln		Germany	50924
28	Zerbst		Germany	39261
29	Bekescsaba		Hungary	5600
30	Budapest		Hungary	1027
31	Budapest		Hungary	1036
32	Debrecen		Hungary	4032
33	Veszprem		Hungary	H-8200
34	Culiacan		Mexico	80000
35	Guadalajara		Mexico	44340
36	Guadalajara		Mexico	44600
37	Guadalajara		Mexico	44690
38	Leon		Mexico	37320
39	Merida		Mexico	97000
40	Mexicali		Mexico	21100
41	Mexico City		Mexico	06700
42	Mexico		Mexico	44620
43	Monterrey, NL		Mexico	64000
44	Lima		Peru	41
45	Lima		Peru	Lima 1
46	Lima		Peru	Lima 25
47	Lima		Peru	Lima 27
48	Lima		Peru	Lima 34
49	Lima		Peru	Lima 41
50	San Isidro		Peru	L27 Lima
51	San Isidro		Peru	Lima 27
52	Bialystok		Poland	15-099
53	Bialystok		Poland	15-461
54	Elblag		Poland	82-300
55	Koscian		Poland	64-000
56	Krakow		Poland	30-510
57	Lublin		Poland	20-607
58	Warszawa		Poland	02-653
59	Baia Mare		Romania	430031
60	Bucharest		Romania	010584
61	Bucharest		Romania	011172
62	Cluj-Napoca		Romania	400006
63	Galati		Romania	800578
64	Torrelavega	Cantabria	Spain	39300
65	A Coruna	La Coruña	Spain	15006
66	Seville	Sevilla	Spain	41071
67	S. Cristobal de la Laguna	Tenerife	Spain	38320