Phase 2
Completed N=40
Study to Evaluate the Safety, PK, PD and Efficacy of AMG 827 in Adults With Rheumatoid Arthritis
Source: ClinicalTrials.gov NCT00771030 ↗Enrolled (actual)
40
Serious AEs
5.0%
Results posted
Nov 2021
Primary outcomePrimary: Number of Participants With Treatment-emergent Adverse Events — 3; 4; 5; 5 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment-emergent Adverse Events |
3; 4; 5; 5; 4; 5 | — |
| PRIMARY Number of Participants With Clinically Significant Changes in Safety Laboratory Tests |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Changes in Physical Examination Findings, Vital Signs, or Electrocardiogram Findings |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Anti-brodalumab Antibodies |
0; 0; 1; 0; 1; 0 | — |
| SECONDARY Time to Maximum Concentration of Brodalumab After Single and Multiple Subcutaneous Doses |
1.46; 3.96; 2.99; 2.00; 3.95; 4.00 | — |
| SECONDARY Maximum Concentration of Brodalumab After Single and Multiple Subcutaneous Doses |
0.742; 5.67; 16.6; 1.35; 5.93; 18.4 | — |
| SECONDARY 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 |
1.77; 37.6; 142; 4.13; 50.8; 191 | — |
| SECONDARY Accumulation Ratio for Brodalumab After Subcutaneous Dosing |
24.4; 1.3; 1.5 | — |
| SECONDARY Time to Maximum Concentration of Brodalumab After Single and Multiple Intravenous Doses |
4.07; 0.92; 0.98; 0.83 | — |
| SECONDARY Maximum Concentration of Brodalumab After Single and Multiple Intravenous Doses |
111; 240; 127; 655 | — |
| SECONDARY 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 Intravenous Doses |
831; 1840; 951; 2230 | — |
| SECONDARY Accumulation Ratio for Brodalumab After Intravenous Dosing |
1.1; 1.2 | — |
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT00771030). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.