Rheumatoid ArthritisPhase 2NCT00950989
Brodalumab (AMG 827) in Rheumatoid Arthritis (RA) Participants With Inadequate Response to Methotrexate
A Phase 2 study testing Brodalumab, Methotrexate and folic acid in people with Rheumatoid Arthritis, run by Amgen.
Trial summary
Study in participants with RA who have an inadequate response to methotrexate. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Brodalumab, Methotrexate and folic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 252 participants
- Where
- No sites listed yet
- Study dates
- 30 Dec 2009to 11 Feb 2011
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 10Show fewer
- 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
About this study
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
Study in participants with RA who have an inadequate response to methotrexate.
- Conditions
- Rheumatoid Arthritis
- Being tested
- Brodalumab, Placebo, Methotrexate, folic acid
- Keywords
- Autoimmune Diseases, Musculoskeletal Diseases, Joint Diseases, Arthritis, Connective Tissue Diseases, Arthritis, Rheumatoid, Rheumatic Diseases
- Medical subject headings
- Arthritis, Rheumatoid, Autoimmune Diseases, Musculoskeletal Diseases, Joint Diseases, Arthritis, Connective Tissue Diseases, Rheumatic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrodalumabDrug
Also called AMG 827
3 single subcutaneous (SC) injections at day 1 and weeks 1, 2, 4, 6, 8, and 10
PlaceboDrug
3 single SC injections at day 1 and weeks 1, 2, 4, 6, 8, and 10
MethotrexateDrug
Two methotrexate dose adjustments were allowed in the event of methotrexate toxicity, however, doses < 7.5 mg/week necessitated discontinuation from study.
folic acidDietary supplement
at least 5 mg per week
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week). Receives: Drug: Placebo; Drug: Methotrexate; Dietary Supplement: folic acid |
| Brodalumab 70 mg | Experimental | 70 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week). Receives: Drug: Brodalumab; Drug: Methotrexate; Dietary Supplement: folic acid |
| Brodalumab 140 mg | Experimental | 140 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexateand folic acid supplementation (at least 5 mg per week). Receives: Drug: Brodalumab; Drug: Methotrexate; Dietary Supplement: folic acid |
| Brodalumab 210 mg | Placebo comparator | 210 mg brodalumab on day 1 and weeks 1, 2, 4, 6, 8, and 10 for a total of 7 doses plus a stable weekly dose of methotrexate and folic acid supplementation (at least 5 mg per week). Receives: Drug: Brodalumab; Drug: Methotrexate; Dietary Supplement: folic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, week 12
Secondary outcomes (7)
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.
Measured: Baseline, Week 12
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.
Measured: Baseline, week 12
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.
Measured: Week 12
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.
Measured: From first dose of study drug until the end of study; median (min, max) duration was 113 days (8, 132).
Pharmacokinetics (PK) of Brodalumab: Maximum Observed Concentration (Cmax)
Measured: Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose
PK of Brodalumab: Time to Maximum Observed Concentration (Tmax)
Measured: Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose
PK of Brodalumab: Area Under the Curve During the Dosing Interval (AUCtau)
Measured: Week 8: Day 59-Day 61 (44-100 hours post-dose), Day 64 (160-176 hours post-dose), Week 10: pre-dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2009 (estimated)
- Study start30 Dec 2009
- Primary completion11 Feb 2011
- Study completion11 Feb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 252 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00950989
- Sponsor's protocol ID
- 20090061
- Status last verified
- Nov 2021
- First submitted
- 30 Jul 2009
- Last updated
- 21 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
Publications
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.
PubMed 25877498