Brodalumab (AMG 827) in Rheumatoid Arthritis (RA) Participants With Inadequate Response to Methotrexate

Rheumatoid Arthritis Clinical Trial

Official title:

A Randomized, Double-blind, Placebo-controlled, Multiple-dose Study to Evaluate the Safety, Tolerability, and Efficacy of AMG 827 in Subjects With Rheumatoid Arthritis and an Inadequate Response to Methotrexate

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00950989
• Other study ID #: 20090061
• Status: Completed
• Phase: Phase 2
• Start date: December 30, 2009
• Est. completion date: February 11, 2011

Study information

• Verified date: November 2021
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Study in participants with RA who have an inadequate response to methotrexate.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 252
• Est. completion date: February 11, 2011
• Est. primary completion date: February 11, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Active RA for least 6 months

• Current RA defined as = 6 swollen joints (out of 66 joints examined) and = 8 tender/painful joints (out of 68 joints examined) at screening and baseline (swollen and tender/painful joint count must not include distal interphalangeal joints) and at least 1 of the following at screening: Erythrocyte sedimentation rate = 28 mm or C-reactive protein > 15 mg/L

• At least 1 of the following at screening: Rheumatoid factor positive or Anti-cyclic citrullinated peptide antibody positive

• Currently taking methotrexate for = 12 weeks and on a stable dose of methotrexate at 15 to 25 mg weekly for = 4 weeks at day -1.

Exclusion Criteria:

• Prosthetic joint infection within 5 years of screening or native joint infection within 1 year of screening

• Class IV RA

• Felty's syndrome

• Presence of serious infection

• Significant concurrent medical conditions

• Pregnant or breast feeding

• Significant Laboratory abnormalities

• Any disease-modifying anti-rheumatic drug (DMARD) other than methotrexate within 28 days

• Leflunomide or live vaccines within 3 months

• Previous use of any experimental or commercially available biologic DMARD

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Drug:
• Brodalumab
3 single subcutaneous (SC) injections at day 1 and weeks 1, 2, 4, 6, 8, and 10
• Placebo
3 single SC injections at day 1 and weeks 1, 2, 4, 6, 8, and 10
• Methotrexate
Two methotrexate dose adjustments were allowed in the event of methotrexate toxicity, however, doses < 7.5 mg/week necessitated discontinuation from study.

Dietary Supplement:
• folic acid
at least 5 mg per week

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

References & Publications (1)

Pavelka K, Chon Y, Newmark R, Lin SL, Baumgartner S, Erondu N. A study to evaluate the safety, tolerability, and efficacy of brodalumab in subjects with rheumatoid arthritis and an inadequate response to methotrexate. J Rheumatol. 2015 Jun;42(6):912-9. doi: 10.3899/jrheum.141271. Epub 2015 Apr 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response at Week 12	A positive ACR50 response is defined if the following 3 criteria for improvement from baseline were met: 50% improvement in 68 tender joint count; 50% improvement in 66 swollen joint count; and; 50% improvement in at least 3 of the 5 following parameters: Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]),; Patient's global assessment of disease activity (measured on a 0-10 Likert scale),; Physician's global assessment of disease activity (measured on a 0-10 Likert scale),; Patient's self assessment of disability (Health Assessment Questionnaire - Disability Index [HAQ-DI]),; Acute phase reactant: erythrocyte sedimentation rate (ESR) or C-Reactive Protein (CRP), whichever has bigger improvement.	Baseline, week 12
Secondary	Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response at Week 12	A positive ACR20 response is defined if the following 3 criteria for improvement from baseline were met: 20% improvement in 68 tender joint count; 20% improvement in 66 swollen joint count; and; 20% improvement in at least 3 of the 5 following parameters: Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]),; Patient's global assessment of disease activity (measured on a 0-10 Likert scale),; Physician's global assessment of disease activity (measured on a 0-10 Likert scale),; Patient's self assessment of disability (Health Assessment Questionnaire - Disability Index [HAQ-DI]),; Acute phase reactant: erythrocyte sedimentation rate (ESR) or C-Reactive Protein (CRP), whichever has bigger improvement.	Baseline, Week 12
Secondary	Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response at Week 12	A positive ACR70 response is defined if the following 3 criteria for improvement from baseline were met: 70% improvement in 68 tender joint count; 70% improvement in 66 swollen joint count; and; 70% improvement in at least 3 of the 5 following parameters: Patient's assessment of joint pain (measured on a 100 mm visual analog scale [VAS]),; Patient's global assessment of disease activity (measured on a 0-10 Likert scale),; Physician's global assessment of disease activity (measured on a 0-10 Likert scale),; Patient's self assessment of disability (Health Assessment Questionnaire - Disability Index [HAQ-DI]),; Acute phase reactant: erythrocyte sedimentation rate (ESR) or C-Reactive Protein (CRP), whichever has bigger improvement.	Baseline, week 12
Secondary	Disease Activity Score 28 (DAS28) at Week 12	The DAS28 is a composite score to measure disease activity in patients with rheumatoid arthritis, derived from the following variables: • The number of tender joints assessed using the 28-jount count and number of swollen joints assessed using the 28-joint count; • Erythrocyte sedimentation rate (ESR); • Patient's global assessment of disease activity (measured on a 0-10 Likert scale). The DAS28 score ranges from 0 to 10, with higher scores indicating more severe disease activity.	Week 12
Secondary	Number of Participants With Treatment Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation	AEs are defined as any untoward medical occurrence, that does not necessarily have a causal relationship with this treatment. SAEs are defined as an AE that: is fatal; is life threatening (places the subject at immediate risk of death); requires in-patient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; other significant medical hazard. The severity of events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) v 4.0: mild=grade 1, moderate=grade 2, severe=grade 3, life-threatening=grade 4, death=grade 5.	From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
Secondary	Pharmacokinetics (PK) of Brodalumab: Maximum Observed Concentration (Cmax)		Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose
Secondary	PK of Brodalumab: Time to Maximum Observed Concentration (Tmax)		Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose
Secondary	PK of Brodalumab: Area Under the Curve During the Dosing Interval (AUCtau)		Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose

External Links

•   AmgenTrials clinical trials website