Study to Evaluate the Safety, PK, PD and Efficacy of AMG 827 in Adults With Rheumatoid Arthritis

Amgen

Status and phase: Completed; Phase 2; Phase 1

Conditions: Rheumatoid Arthritis

Treatments: Other: Placebo; Biological: Brodalumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT00771030

20070264

Details and patient eligibility

About

This Phase 1b/2a study will evaluate safety, tolerability pharmacokinetics (PK) and pharmacodynamics (PD) of brodalumab when administered in multiple subcutaneous (SC) and intravenous (IV) doses in patients with active rheumatoid arthritis (RA) in combination with a stable dose of disease modulating anti-rheumatic drugs (DMARDs). Part A is dose escalation (to assess safety & tolerability), and Part B is dose expansion (to assess clinical efficacy) at the highest tolerated dose level of brodalumab from Part A.

Full description

The dose-escalation phase consisted of 5 sequentially enrolled dose cohorts. Within each cohort participants were randomly assigned in a 3:1 ratio to receive brodalumab or placebo subcutaneously (cohorts 1 to 3) or intravenously (cohorts 5 and 6).

Dose escalations required acceptable safety data based on blinded review following completion of the day 15/week 3 visit by the final participant in each cohort and when six or more participants in a cohort had been administered at least three doses of brodalumab (cohorts 1, 2, 3 and 5). In cohort 6, dose escalation followed completion of the day 15/week 3 visit by the final patient in cohort 5 and six or more participants in cohort 5 had been administered two or more IV infusions of brodalumab.

Cohort 4 was designed to be used in the dose expansion phase to provide evidence of biological impact in 70 patients with RA receiving brodalumab at the dose determined during the dose escalation phase of the study. This cohort was not enrolled because a decision was made not to conduct Part B of the study; instead a separate phase 2 multiple-dose study was conducted to evaluate efficacy of brodalumab in patients with RA (Study 20090061; NCT00950989).

Enrollment: 40 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female between 18 to 70 years of age, inclusive at the time of screening
• Diagnosed with RA as determined by meeting 1987 American College of Rheumatology (ACR) classification criteria
• Active RA defined as ≥ 6 swollen joints (out of 66 joints examined) and ≥ 8 tender/painful joints (out of 68 joints examined) and at least 1 of the following:
• Erythrocyte sedimentation rate (ESR) ≥ 28 mm, or
• C-reactive protein (CRP) > 15 mg/L, or
• Morning stiffness > 45 minutes (applicable to subjects in Part A ONLY)
• Duration of RA for at least 6 months
• Currently taking methotrexate (MTX) consecutively for ≥ 12 weeks and on a stable dose of oral or SC MTX at 15-25 mg weekly for ≥ 4 weeks at day -1. A lower MTX dose is acceptable if it is the highest tolerated dose, however, toxicity documentation by the Investigator is required. All subjects will take folic acid to minimize toxicity, according to local guidelines.
• Additional Inclusion Criteria Apply

Exclusion criteria

• History or evidence of a clinically significant disorder other than RA (including but not limited to cardiopulmonary, oncologic, renal, metabolic, hematologic or psychiatric), condition or disease that, in the opinion of the Investigator and Amgen physician would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
• Uncontrolled, clinically significant systemic disease other than RA such as diabetes mellitus, liver disease, asthma, cardiovascular disease or hypertension
• Malignancy within 5 years (except successfully treated in situ cervical cancer or squamous or basal cell carcinoma of the skin)
• Presence of a serious or chronic infections
• Subject (male or female) is not willing to use highly effective contraception, defined as a double barrier method (ie, spermicidal jelly and condom, or condom and diaphragm) during treatment and up to end of study
• Additional Exclusion Criteria Apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Quadruple Blind

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40 participants in 7 patient groups, including a placebo group

Placebo SC (Cohorts 1-3)

Placebo Comparator group

Description:

Participants received placebo to brodalumab by subcutaneous (SC) injection once every 2 weeks for a total of six doses.

Treatment:

Other: Placebo

Placebo IV (Cohorts 5-6)

Placebo Comparator group

Description:

Participants received placebo to brodalumab by intravenous (IV) infusion every 4 weeks for a total of two doses.

Treatment:

Other: Placebo

Brodalumab 50 mg SC (Cohort 1)

Experimental group

Description:

Participants received 50 mg brodalumab by subcutaneous injection once every 2 weeks for a total of six doses.

Treatment:

Biological: Brodalumab

Brodalumab 140 mg SC (Cohort 2)

Experimental group

Description:

Participants received 140 mg brodalumab by subcutaneous injection once every 2 weeks for a total of six doses.

Treatment:

Biological: Brodalumab

Brodalumab 210 mg SC (Cohort 3)

Experimental group

Description:

Participants received 210 mg brodalumab by subcutaneous injection once every 2 weeks for a total of six doses.

Treatment:

Biological: Brodalumab

Brodalumab 420 mg IV (Cohort 5)

Experimental group

Description:

Participants received 420 mg brodalumab by IV infusion once every 4 weeks for a total of two doses.

Treatment:

Biological: Brodalumab

Brodalumab 700 mg IV (Cohort 6)

Experimental group

Description:

Participants received 700 mg brodalumab by IV infusion once every 4 weeks for a total of two doses.

Treatment:

Biological: Brodalumab