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

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-012566-32-LV
• Date of registration: 30/10/2009
• Prospective Registration: Yes
• Primary sponsor: Amgen Inc
• Public 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
• Scientific 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
• Date of first enrolment: 29/12/2009
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-012566-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Bulgaria, Czech Republic, Hungary, Latvia, Poland, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Subject is capable of understanding and giving written, voluntary informed consent before study screening
Male or female = 18 and = 70 years of age at time of screening
Subject is diagnosed with RA as determined by meeting 1987 American College of Rheumatology (ACR) classification criteria
Subject has active 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 [DIPs] joints) and at least 1 of the following at screening:
- ESR = 28 mm
- CRP > 15 mg/L
Subject has at least 1 of the following at screening:
- Rheumatoid factor (RF) positive
- Anti-cyclic citrullinated peptide (anti-CCP) antibody positive
Subject has had RA for at least 6 months
Subject has a negative test for hepatitis B virus (HBV) surface antigen, hepatitis C virus (HCV) antibody, and human immunodeficiency virus (HIV)
Subject, if female and not at least 3 years postmenopausal or surgically
sterile, has a negative serum pregnancy test within 4 weeks before
initiating IP and a negative urine pregnancy test at baseline
Subject is currently taking methotrexate consecutively for = 12 weeks and on a
stable dose of methotrexate at 15 to 25 mg weekly for = 4 weeks at day -1. A
lower methotrexate dose is acceptable (but no lower than 10 mg per week) if it is
the highest tolerated dose, however, toxicity documentation by the investigator is
required. Toxicities that would permit use of a lower dose of methotrexate
include hepatic, gastrointestinal, mucosal, and hematologic. All subjects must
take folic acid to minimize toxicity (at least 5 mg per week).
If the subject is currently taking non-steroidal anti-inflammatory drugs (NSAIDs),
the subject must be on stable use (eg, PRN use of a stable dose) = 4 weeks prior
to screening.
If the subject is currently taking oral corticosteroids (not to exceed the equivalent
of 10 mg of prednisone per day), the subject must be on a stable dose = 4 weeks
prior to screening.
Subject has had a chest radiograph within 3 months prior to the first
administration of IP that does not demonstrate abnormalities suggestive of a
malignancy or current active infection, including tuberculosis
Subject has a negative purified protein derivative (PPD; Tuberculin) test
within 4 weeks before initiating IP. Tuberculin skin tests are considered
positive when they have = 5 mm of induration at 48 to 72 hours after test is placed. Subjects with a positive tuberculin skin test (if = 14 mm of
induration) are allowed if they meet all of the following criteria:
- a history of Bacillus Calmette-Guerin vaccination
- a negative Quantiferon test in the past year
- no symptoms per tuberculosis worksheet
- a negative chest radiograph
Note: subjects with a history of a positive PPD may refuse a repeat PPD
and be allowed to continue screening for tuberculosis as above.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Rheumatoid arthritis related
Subject had prosthetic joint infection within 5 years of screening or native joint infection within 1 year of screening
Subject has Class IV RA according to ACR revised response criteria (see
Appendix C)
Subject is diagnosed with Felty’s syndrome (RA, splenomegaly and granulocytopenia)
Subject has a planned surgical intervention for a pretreatment condition within the duration of the study, including the follow up period
Other medical conditions
Subject has any active CTC grade 2 or higher infection (including chronic or localized infections) within 30 days prior to screening, at screening, or during screening period prior to first investigational product (IP) dose
Subject has a serious infection, defined as requiring hospitalization or IV antibiotics within 8 weeks before screening
Subject has recurrent or chronic infections, defined as = 3 infections requiring anti-microbials over the past 12 months prior to screening
Subject has one or more significant concurrent medical conditions, including:
- Type 1 diabetes
- Poorly controlled type 2 diabetes (hemoglobin A1c > 8.0)
- Symptomatic heart failure (New York Heart Association class II, III, or IV)
- Myocardial infarction within the last year
- Current or history of unstable angina pectoris within the last year
- Uncontrolled hypertension as defined by a resting blood pressure
= 160/95 mmHg prior to randomization (confirmed by a repeat assessment)
- Severe chronic pulmonary disease (eg, requiring oxygen therapy)
- Major chronic inflammatory disease or connective tissue disease other than RA (eg, systemic lupus erythematosus), with the exception of secondary Sjögren’s syndrome
- Multiple sclerosis or any other demyelinating disease
- Active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma, or history of cancer (except successfully treated in situ cervical cancer or squamous or basal cell carcinoma of the skin).
- History of alcoholic liver disease
- Any condition that, in the opinion of the investigator, might cause this study to
be detrimental to the subject
Subject is pregnant or breast feeding, or planning to become pregnant while enrolled in the study, up to the subject’s last study visit including the follow-up
period
Female subject is not willing to abstain from sexual intercourse or use 2 highly
effective forms of birth control for the duration of the study including the follow-up
period (except women at least 3 years postmenopausal or surgically sterile).
Highly effective methods of birth control for women include but are not limited to
birth control pills, Depo-Provera® injections, contraceptive implants, or occlusive
cap (barrier method) in combination with barrier methods used by the man.
Male subject is not willing to abstain from sexual intercourse or use 2 highly
effective forms of birth control for the duration of the study including the follow-up
period, plus an additional 10 weeks (except for men who are surgically sterile or
whose female partners are at least 3 years postmenopausal or surgically sterile).
Highly effective methods of birth control include but are not limited to a condom
in combination with hormonal birth control or barrier methods used by the
woman.
Male subject (including vasectomised males) with a pregnant female partner is
not willing to use effective methods to ensure that an unborn child is not exposed
to AMG 827 via semen. Effective methods to ensure that an unborn child is not
e

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid arthritis (RA)
MedDRA version: 12.0 Level: LLT Classification code 10039073 Term: Rheumatoid arthritis

Intervention(s)

Product Name: AMG 827
Product Code: AMG 827
Pharmaceutical Form: Solution for injection
INN or Proposed INN: AMG 827
Current Sponsor code: AMG 827
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 70-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Main Objective: To evaluate the efficacy of AMG 827 compared with placebo as measured by the proportion of subjects achieving an American College of Rheumatology (ACR) 50
response at week 12.

Secondary Objective: To evaluate the efficacy of AMG 827 as measured by the following:
- The proportion of subjects with an ACR 20 and 70 at week 12
- Disease Activity Score 28 joint (DAS28) at week 12
To evaluate the short term safety profile of AMG 827 in subjects with rheumatoid
arthritis (RA)
To characterize the pharmacokinetics (PK) of AMG 827 in subjects with RA

Primary end point(s): The primary efficacy endpoint is the ACR 50 response at Week 12.

Secondary ID(s)

20090061

2009-012566-32-CZ