Atacicept in Anti-Tumor Necrosis Factor Alpha-naïve Subjects With Rheumatoid Arthritis (AUGUST II)

A Randomised, Double-blind, Placebo Controlled, Multi-centre Phase II Study of Atacicept in Anti-TNFα-naïve Patients With Moderate to Severely Active Rheumatoid Arthritis and an Inadequate Response to Methotrexate

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00595413

Acronym

AUGUST II

Enrollment

311

Registered

2008-01-16

Start date

2007-09-30

Completion date

2009-10-31

Last updated

2016-02-17

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid arthritis, Atacicept, Adalimumab, Humira®

Brief summary

The primary objective of this study is to evaluate the efficacy of atacicept compared to placebo in the treatment of signs and symptoms in a subject population with active rheumatoid arthritis (RA), inadequate response to methotrexate (MTX) and no previous exposure to anti-tumor necrosis factor alpha (anti-TNFalpha) therapy.

Interventions

DRUGPlacebo matched to atacicept

Placebo matched to atacicept will be administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.

DRUGAtacicept: with loading dose

Atacicept will be administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks.

DRUGAtacicept

Atacicept will be administered subcutaneously at a dose of 150 mg once a week for 25 weeks.

BIOLOGICALAdalimumab

Adalimumab (Humira®) will be administered subcutaneously at a dose of 40 mg every other week for 25 weeks.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Male or female subjects greater than or equal to (\>=) 18 years of age at the time of informed consent who have RA satisfying American College of Rheumatology (ACR) criteria with a disease history of at least 6 months * Subjects must have active disease, defined by \>=8 swollen joints (out of 66), \>=8 tender joints (out of 68) and CRP \>=10 milligram per liter (mg/L) and/or erythrocyte sedimentation rate (ESR) \>=28 millimeter per hour (mm/hr), despite treatment with MTX at a dose of \>=15 milligram per week (mg/week) for greater than (\>) 3 months * Other protocol-defined inclusion criteria could apply

Exclusion criteria

* Inflammatory joint disease other than RA * Previous or concurrent treatment with any approved or investigational biological compound for RA, including but not restricted to any anti-TNFalpha agents, rituximab, abatacept, tocilizumab, interleukin-1 receptor antagonist (IL-1Ra) and belimumab * Treatment with disease-modifying anti-rheumatic drug (DMARDs) other than MTX * Participation in any interventional clinical trial within 1 month before study Day 1 * MTX dose \>25 mg/week, prednisone dose \>10 mg/day (or equivalent), or change in steroid or non-steroidal anti-inflammatory drug (NSAID) dosing regimen within 28 days before study Day 1 * Immunization with live vaccine or immunoglobulin (Ig) treatment within 28 days before study Day 1 or need for such treatment during the study (including follow-up) * Any history or presence of active or latent tuberculosis, major infection requiring hospitalization or intravenous anti-infectives within 28 days before study Day 1 * Other major concurrent illness or organ dysfunction as specified in the protocol * Serum IgG below 6 gram per liter (g/L) * Known hypersensitivity to atacicept or to any of the components of the formulated atacicept * Other protocol-defined

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP) at Week 26	Week 26	ACR20-CRP response is defined as greater than or equal to (\>=) 20 percent (%) improvement from Baseline in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with \>=20% improvement from Baseline in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).

Secondary

Measure	Time frame	Description
Percentage of Participants Achieving American College of Rheumatology 50 Response Based on CRP (ACR50-CRP) at Week 26	Week 26	ACR50-CRP response is defined as \>=50% improvement from Baseline in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with \>=50% improvement from Baseline in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).
Percentage of Participants Achieving American College of Rheumatology 70 Response Based on CRP (ACR70-CRP) at Week 26	Week 26	ACR70-CRP response is defined as \>=70% improvement from Baseline in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with \>=70% improvement from Baseline in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).
Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Responses at Week 26	Week 26	The EULAR response criteria evaluate change in DAS28 scores represented as good response, moderate response, or no response considering both the current DAS28 score and the observed improvement from baseline. Participants were considered to have good or moderate EULAR response if at the time of assessment, their DAS28 score was less than or equal to (\<=) 5.1 and the improvement from baseline in their DAS28 score was greater than (\>) 0.6; or if at the time of assessment, their DAS28 score was \>5.1 and improvement from baseline in their DAS28 score was \>1.2.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs	From the first dose of study drug up to 30 days after the last dose of study drug, assessed up to Week 38	An adverse event (AE) was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.

Countries

Germany, United States

Participant flow

Participants by arm

Arm	Count
Placebo Placebo matched to atacicept was administered subcutaneously twice a week for initial 4 weeks, followed by once a week for subsequent 21 weeks.	76
Atacicept 150 mg With Loading Dose Atacicept was administered subcutaneously at a dose of 150 milligram (mg) twice a week for initial 4 weeks as loading dose, followed by 150 mg once a week for subsequent 21 weeks.	78
Atacicept 150 mg Without Loading Dose Atacicept was administered subcutaneously at a dose of 150 mg once a week for 25 weeks. Participants also received placebo matched to atacicept subcutaneously once a week during initial 4 weeks for blinding purpose (placebo injections alternating with atacicept injections).	78
Adalimumab Adalimumab (Humira®) was administered subcutaneously at a dose of 40 mg every other week for 25 weeks.	79
Total	311

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003
Overall Study	Adverse Event	0	2	1	1
Overall Study	Death	0	0	1	0
Overall Study	Lost to Follow-up	2	2	1	3
Overall Study	Other	5	1	5	0

Baseline characteristics

Characteristic	Placebo	Atacicept 150 mg With Loading Dose	Atacicept 150 mg Without Loading Dose	Adalimumab	Total
Age, Continuous	54.0 years STANDARD_DEVIATION 10.3	53.0 years STANDARD_DEVIATION 11.3	53.3 years STANDARD_DEVIATION 13.2	53.3 years STANDARD_DEVIATION 11.5	53.4 years STANDARD_DEVIATION 11.6
Sex: Female, Male Female	64 Participants	65 Participants	66 Participants	64 Participants	259 Participants
Sex: Female, Male Male	12 Participants	13 Participants	12 Participants	15 Participants	52 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —
other Total, other adverse events	23 / 76	27 / 78	24 / 78	22 / 79
serious Total, serious adverse events	2 / 76	4 / 78	7 / 78	3 / 79

Outcome results

Primary

Percentage of Participants Achieving American College of Rheumatology 20 Response Based on C-reactive Protein (ACR20-CRP) at Week 26

ACR20-CRP response is defined as greater than or equal to (\>=) 20 percent (%) improvement from Baseline in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with \>=20% improvement from Baseline in at least 3 of the following 5 measures: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function; and 5) acute-phase marker (CRP).

Time frame: Week 26