AMG 827 in Subjects With Psoriatic Arthritis

A Randomized, Double-blinded, Placebo-controlled, Multiple-dose Study With an Open Label Extension to Evaluate the Safety and Efficacy of AMG 827 in Subjects With Psoriatic Arthritis.

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01516957

Enrollment

168

Registered

2012-01-25

Start date

2011-10-31

Completion date

2015-09-30

Last updated

2020-08-27

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

Conditions

Psoriatic Arthritis

Keywords

Psoriatic Arthritis, IL-17, AMG 827, AMG827, Musculoskeletal Disease, Spondylarthropathy

Brief summary

The study will examine the safety and effectiveness of AMG 827 for the treatment of psoriatic arthritis

Detailed description

The study will examine the safety and effectiveness of AMG 827 for the treatment of psoriatic arthritis. Patients will randomly receive either AMG 827 or placebo (a look-a-like liquid that does not have any drug in it) and neither the doctor nor the patient will know what treatment is being given.

Interventions

DRUGAMG 827 140

140 mg AMG 827 SC (subcutaneous)

DRUGPlacebo

Placebo SC (subcutaneous)

DRUGAMG 827 280

280 mg AMG 827 SC (subcutaneous)

DRUGAMG 827 210

210 mg AMG 827 SC (subcutaneous)

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Inclusion criteria

* Subject has had a diagnosis of psoriatic arthritis (by the Classification of Psoriatic Arthritis (CASPAR) criteria) for at least 6 months * Subject has ≥ 3 tender and ≥ 3 swollen joints

Exclusion criteria

* Subject has an active infection or history of infections (systemic anti-infectives were used within 28 days; requiring hospitalization or intravenous anti-infectives within 8 weeks; recurrent or chronic) * Significant concurrent medical conditions * Pregnant or breast feeding * Significant Laboratory abnormalities * Use of sulfasalazine, hydroxychloroquine, systemically administered calcineurin inhibitors, azathioprine, parenteral corticosteroids including intramuscular or intraarticular administration, or live vaccines within 28 days * Use of anti-TNF therapy within 2 months * Use of an anti-interleukin (IL)12/IL-23 drug or other experimental or commercially available biologic therapies for psoriasis and/or psoriatic arthritis within 3 months * Prior use of rituximab * Prior use of anti-IL-17 biologic therapy, including AMG 827

Design outcomes

Primary

Measure	Time frame	Description
To Evaluate the Efficacy of AMG 827 in Psoriatic Arthritis as Measured by the Proportion of Subjects Achieving an American College of Rheumatology (ACR) 20%	Baseline to week 12	To evaluate the efficacy of AMG 827 in psoriatic arthritis as measured by the proportion of subjects achieving an American College of Rheumatology (ACR) 20% response at week 12. ACR20 responders are subjects with 20% improvement from baseline based off of percent changes in tender/painful joint count, swollen joint counts, physician global assessment of disease activity, and health assessment questionnaire-disability index.

Secondary

Measure	Time frame	Description
To Evaluate the Efficacy of AMG 827 in Psoriatic Arthritis as Measured by the Proportion of Subjects Achieving an ACR 50	Baseline to week 12	To evaluate the efficacy of AMG 827 in psoriatic arthritis as measured by the proportion of subjects achieving an ACR 50 response at week 12. ACR50 responders are subjects with 50% improvement from baseline based off of percent changes in tender/painful joint count, swollen joint counts, physician global assessment of disease activity, and health assessment questionnaire-disability index.
To Evaluate the Efficacy of AMG 827 in Psoriatic Arthritis as Measured by the Proportion of Subjects Achieving an ACR 70	Baseline to week 12	To evaluate the efficacy of AMG 827 in psoriatic arthritis as measured by the proportion of subjects achieving an ACR 70 response at Week 12. ACR70 responders are subjects with 70% improvement from baseline based off of percent changes in tender/painful joint count, swollen joint counts, physician global assessment of disease activity, and health assessment questionnaire-disability index.
To Evaluate the Efficacy of AMG 827 in Psoriatic Arthritis as Measured by Change From Baseline in Clinical Disease Activity Index (CDAI)	Baseline to week 12	To evaluate the efficacy of AMG 827 in psoriatic arthritis as measured by Clinical Disease Activity Index (CDAI) change from baseline at week 12. CDAI = SJC(28) + TJC(28) + PGA + EGA * SJC(28): Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees) * TJC(28): Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees) * PGA: Patient Global disease Activity (patient's self assessment of overall RA disease activity on a scale 1-10 where 10 is maximal activity) A CDAI reduction of 6.5 represents moderate improvement. * EGA: Evaluator's Global disease Activity (evaluator's assessment of overall RA disease activity on a scale 1-10 where 10 is maximal activity)
To Evaluate the Efficacy of AMG 827 in Psoriatic Arthritis as Measured by Change From Baseline in Disease Activity Score With a 28 Joint Count (DAS 28)	Baseline to week 12	To evaluate the efficacy of AMG 827 in psoriatic arthritis as measured by Disease Activity Score with a 28 joint count (DAS 28) change from baseline at week 12. The DAS28 is a composite score derived from 4 measures. To calculate the DAS28: 1. count the number of swollen joints (out of the 28), 2. count the number of tender joints (out of the 28), 3. take blood to measure the erythrocyte sedimentation rate (ESR) or C reactive protein (CRP), 4. ask the participant to make a 'global assessment of health' (indicated by marking a 10 cm line between very good and very bad). These results are then fed into a complex mathematical formula to produce the overall disease activity score. A DAS28 of greater than 5.1 implies active disease, less than 3.2 low disease activity, and less than 2.6 remission.

Countries

Canada, United States

Participant flow

Recruitment details

A total of 168 subjects were enrolled in the double-blind phase of the study. Of these 168 subjects, 156 entered the open-label extension phase (52 subjects were previously dosed with placebo, 53 subjects with brodalumab 140 mg Q2W, and 51 subjects with brodalumab 280 mg Q2W).

Participants by arm

Arm	Count
Placebo SC Placebo Placebo: Placebo SC (subcutaneous)	52
AMG 827 140 140 mg AMG 827 AMG 827 140: 140 mg AMG 827 SC (subcutaneous)	53
AMG 827 280 280 mg AMG 827 AMG 827 280: 280 mg AMG 827 SC (subcutaneous)	51
Total	156

Baseline characteristics

Characteristic	Placebo SC	AMG 827 140	AMG 827 280	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	9 Participants	5 Participants	7 Participants	21 Participants
Age, Categorical Between 18 and 65 years	43 Participants	48 Participants	44 Participants	135 Participants
Age, Continuous	53.4 years STANDARD_DEVIATION 13.2	52.8 years STANDARD_DEVIATION 9.3	50.5 years STANDARD_DEVIATION 11.8	52.3 years STANDARD_DEVIATION 11.5
Sex: Female, Male Female	28 Participants	33 Participants	36 Participants	97 Participants
Sex: Female, Male Male	24 Participants	20 Participants	15 Participants	59 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	52 / 52	50 / 53	50 / 51	153 / 156
serious Total, serious adverse events	13 / 52	15 / 53	18 / 51	31 / 156

Outcome results

Primary

To Evaluate the Efficacy of AMG 827 in Psoriatic Arthritis as Measured by the Proportion of Subjects Achieving an American College of Rheumatology (ACR) 20%

To evaluate the efficacy of AMG 827 in psoriatic arthritis as measured by the proportion of subjects achieving an American College of Rheumatology (ACR) 20% response at week 12. ACR20 responders are subjects with 20% improvement from baseline based off of percent changes in tender/painful joint count, swollen joint counts, physician global assessment of disease activity, and health assessment questionnaire-disability index.

Time frame: Baseline to week 12