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

NCT00771030 | Completed Phase 1 Results

• 1 other identifier: 20070264
• Study Type: interventional
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Treatment-emergent Adverse Events

  An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment, including any such occurrence (eg, sign, symptom, or diagnosis) or worsening of a pre-existing medical condition. A serious adverse event was defined as an adverse event that was fatal; was life threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; or other significant medical hazard.

  From first dose of study drug up to end of study (week 19).

• Number of Participants With Clinically Significant Changes in Safety Laboratory Tests

  The investigator reviewed laboratory test results and determined whether an abnormal value in an individual study participant represented a change from prestudy values and determined if changes were clinically significant. The number of participants with clinically significant changes in lab values at any time during the study is reported.

  Blood samples were taken on days 2, 8, 15, 29, 43, 57, 71, 85, 106, and 127.

• Number of Participants With Clinically Significant Changes in Physical Examination Findings, Vital Signs, or Electrocardiogram Findings

  From first dose of study drug up to 4 weeks after last dose; 14 weeks for Cohorts 1, 2, and 3 and 8 weeks for Cohorts 5 and 6.

• Number of Participants With Anti-brodalumab Antibodies

  Samples were tested in a validated immunoassay for the presence of anti-brodalumab binding antibodies. Samples found to be positive for binding antibodies were further tested using a validated cell-based bioassay to determine if the antibodies were able to neutralize the activity of brodalumab.

  Days 1 (pre-dose), 29 (pre-dose), 85, and 127

Secondary Outcomes (8)

• Time to Maximum Concentration of Brodalumab After Single and Multiple Subcutaneous Doses

  After first dose on days 1 (pre-dose and 4 hours post-dose), 2, 3, 5, 8, 11, and 15 (pre-dose), and after last dose on days 71 (pre-dose and 4 hours post-dose), 72, 73, 75, 78, 81, 85, 106 and 127.

• Maximum Concentration of Brodalumab After Single and Multiple Subcutaneous Doses

  After first dose on days 1 (pre-dose and 4 hours post-dose), 2, 3, 5, 8, 11, and 15 (pre-dose), and after last dose on days 71 (pre-dose and 4 hours post-dose), 72, 73, 75, 78, 81, 85, 106 and 127.

• Area Under the Concentration-time Curve From Time Zero to the Time of the Final Quantifiable Sample (AUC0-t) for Brodalumab After Single and Multiple Subcutaneous Doses

  After first dose on days 1 (pre-dose and 4 hours post-dose), 2, 3, 5, 8, 11, and 15 (pre-dose), and after last dose on days 71 (pre-dose and 4 hours post-dose), 72, 73, 75, 78, 81, 85, 106 and 127.

• Accumulation Ratio for Brodalumab After Subcutaneous Dosing

  After first dose on days 1 (pre-dose and 4 hours post-dose), 2, 3, 5, 8, 11, and 15 (pre-dose), and after last dose on days 71 (pre-dose and 4 hours post-dose), 72, 73, 75, 78, 81, 85, 106 and 127.

• Time to Maximum Concentration of Brodalumab After Single and Multiple Intravenous Doses

  After first dose on days 1 (pre-dose and 0.5 and 4 hours post-dose), 2, 3, 5, 8, 11, and 15, and after last dose on days 29 (pre-dose and 0.5 and 4 hours post-dose), 30, 31, 33, 36, 39, 43, 57, 85, 106 and 127.

Study Arms (7)

Placebo SC (Cohorts 1-3)

PLACEBO COMPARATOR

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

Other: Placebo

Placebo IV (Cohorts 5-6)

PLACEBO COMPARATOR

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

Other: Placebo

Brodalumab 50 mg SC (Cohort 1)

EXPERIMENTAL

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

Biological: Brodalumab

Brodalumab 140 mg SC (Cohort 2)

EXPERIMENTAL

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

Biological: Brodalumab

Brodalumab 210 mg SC (Cohort 3)

EXPERIMENTAL

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

Biological: Brodalumab

Brodalumab 420 mg IV (Cohort 5)

EXPERIMENTAL

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

Biological: Brodalumab

Brodalumab 700 mg IV (Cohort 6)

EXPERIMENTAL

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

Biological: Brodalumab

Interventions

Brodalumab BIOLOGICAL

Solution for subcutaneous or intravenous administration

Also known as: AMG 827

Brodalumab 140 mg SC (Cohort 2); Brodalumab 210 mg SC (Cohort 3); Brodalumab 420 mg IV (Cohort 5); Brodalumab 50 mg SC (Cohort 1); Brodalumab 700 mg IV (Cohort 6)

Placebo OTHER

Solution for subcutaneous or intravenous administration

Placebo IV (Cohorts 5-6); Placebo SC (Cohorts 1-3)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Related Publications (1)

• Martin DA, Churchill M, Flores-Suarez L, Cardiel MH, Wallace D, Martin R, Phillips K, Kaine JL, Dong H, Salinger D, Stevens E, Russell CB, Chung JB. A phase Ib multiple ascending dose study evaluating safety, pharmacokinetics, and early clinical response of brodalumab, a human anti-IL-17R antibody, in methotrexate-resistant rheumatoid arthritis. Arthritis Res Ther. 2013 Oct 25;15(5):R164. doi: 10.1186/ar4347.

  PMID: 24286136 DERIVED

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

brodalumab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2008
• First Posted: October 10, 2008
• Study Start: October 27, 2008
• Primary Completion: May 25, 2010
• Study Completion: May 25, 2010
• Last Updated: November 26, 2021
• Results First Posted: November 26, 2021

Record last verified: 2021-10