Safety and Efficacy of AMG 592 in Subjects With Active Rheumatoid Arthritis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03410056
• Date of registration: 03/01/2018
• Prospective Registration: Yes
• Primary sponsor: Amgen
• Public title: Safety and Efficacy of AMG 592 in Subjects With Active Rheumatoid Arthritis
• Scientific title: A Phase 1b/2a Study to Evaluate the Safety and Efficacy of AMG 592 in Subjects With Active Rheumatoid Arthritis With Inadequate Response to Standard of Care Therapy
• Date of first enrolment: May 22, 2018
• Target sample size: 36
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03410056
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 1/Phase 2

Countries of recruitment

Bulgaria, Germany, Poland, Spain, United States

Contacts

• Name: MD
• Affiliation: Amgen

Key inclusion & exclusion criteria

Inclusion Criteria:

- Subject has provided informed consent prior to initiation of any study specific
activities/procedures.

- Age = 18 to = 70 years of age at screening.

- A diagnosis of RA consistent with the 1987 or 2010 American College of Rheumatology
(ACR)/European League Against Rheumatism classification criteria.

- Active RA defined as: Phase 1b: DAS-28-CRP > 2.6 at screening. The 28-joint count
consists of the finger joints excluding the distal interphalangeal joints, the wrists,
elbows, shoulders, and knees. Phase 2a: = 6 swollen joints (based on 66-joint count)
and = 6 tender joints (based on 68-joint count) at screening and baseline. The distal
interphalangeal joint should be evaluated but not included in the total count to
determine eligibility. Additionally, C-reactive protein (CRP) must be greater than the
upper limit of normal (ULN) per the central laboratory at screening.

- Receiving treatment with methotrexate for = 12 weeks and on a stable dose = 15 mg
weekly for = 8 weeks prior to day 1. A lower methotrexate dose is acceptable (but no
lower than 10 mg weekly) if it is the highest tolerated dose and gastrointestinal or
hematologic toxicity at doses = 15 mg weekly is documented by the investigator.

- Receiving treatment with folic or folinic acid per investigator judgment or according
to local standard of care.

- Phase 1b only: Subject may be receiving a stable dose of leflunomide, sulfasalazine,
hydroxychloroquine, minocycline in combination with methotrexate and the dose must be
stable for = 8 weeks prior to day 1.

- Subject may be receiving a stable dose of prednisone = 10mg daily or other equivalent
corticosteroid dose and the dose must be stable for = 2 weeks prior today 1.

- Phase 1b only. Normal or clinically acceptable ECG values (12-lead reporting
ventricular rate and PR, QRS, QT and QTc interval) at screening and baseline based on
opinion of the investigator.

- Immunizations (tetanus, diphtheria, pertussis, seasonal influenza [during flu season],
and pneumococcal [polysaccharide] vaccinations) up to date per local standards as
determined by the investigator.

Exclusion Criteria:

- Class IV RA according to ACR revised response criteria

- Diagnosis of Felty's Syndrome (RA, splenomegaly and granulocytopenia).

- Prosthetic joint infection within 3 years of screening or native joint infection
within 1 year prior to screening.

- Active infection (including chronic or localized infections) for which anti-infectives
were indicated within 4 weeks prior to day 1 OR presence of serious infection, defined
as requiring hospitalization or intravenous anti-infectives within 8 weeks prior to
day 1.

- Known history of active tuberculosis.

- Positive test for tuberculosis during screening defined as either: positive purified
protein derivative (PPD) (= 5 mm of induration at 48 to 72 hours after test is placed)
OR positive Quantiferon test: a positive PPD and a history of Bacillus Calmette-Guérin
vaccination are allowed with a negative Quantiferon test and negative chest x ray; a
positive PPD test (without a history of Bacillus Calmette-Guérin vaccination) or a
positive or indeterminate Quantiferon test are allowed if they have ALL of the
following at screening: no symptoms per tuberculosis or sheet provided by Amgen;
document history of a completed course of adequate prophylaxis(completed treatment for
latent tuberculosis per local standard of care prior to the start of investigational
product); no known exposure to a case of active tuberculosis after most recent
prophylaxis; negative chest X-ray.

- Positive for hepatitis B surface antigen, hepatitis B core antibody (confirmed by
hepatitis B DNA polymerase chain reaction [PCR] test) or detectable hepatitis C virus
RNA by PCR (screening is generally done by hepatitis C antibody [HepCAb], followed by
hepatitis C virus RNA by PCR if HepCAb is positive). A history of hepatitis B
vaccination without history of hepatitis B is allowed.

- Phase 1b only: Positive for Human Immunodeficiency Virus (HIV) at screening or known
to be HIV positive. Phase 2a only: Known history of HIV

- Phase 1b only: Positive drug or alcohol urine test for illicit drugs at screening.
Prescription medications detected by the drug test are allowed if they are being taken
under the direction of a physician.

- Presence of one or more significant concurrent medical conditions per investigator
judgment, including but not limited to the following: poorly controlled diabetes or
hypertension; chronic kidney disease stage IIIb, IV, or V; symptomatic heart failure
(New York Heart Association class II, III, or IV); myocardial infarction or unstable
angina pectoris within the past 12 months prior to randomization; severe chronic
pulmonary disease (eg, requiring oxygen therapy); multiple sclerosis or any other
demyelinating disease; major chronic inflammatory disease or connective tissue disease
other than RA (eg, systemic lupus erythematosus with the exception of secondary
Sjögren's syndrome).

- Malignancy except non-melanoma skin cancers, cervical or breast ductal carcinoma in
situ within the last 5 years.

- History of alcohol or substance abuse within 6 months of screening

- Phase 1b only: Current smoker, and/or use of any nicotine or tobacco containing
products within the last 6 months prior to day 1. These types of products include but
are not limited to: snuff, chewing tobacco, cigars, electronic cigarettes, cigarettes,
pipes, or nicotine patches.

- Phase 1b only: Subject unwilling to limit alcohol consumption to = 1 drink of alcohol
per day and = 3 drinks per week for the duration of the study, where a drink is
equivalent to 12 ounces of regular beer, 8 to 9 ounces of malt liquor, 5 ounces of
wine, or 1.5 ounces of 80 proof distilled spirits. Phase 1b only: Unwilling or unable
to abstain from alcohol consumption within 48 hours prior to each visit (including
screening).

- Subjects who have received intra-articular or systemic corticosteroid injections for
treatment of acute RA flare (not being part of a regular therapeutic regimen) within 4
weeks prior to screening.

- Currently receiving or had treatment with cyclophosphamide, chlorambucil, nitrogen
mustard, or any other alkylating agent = 6 months prior to day 1.

- Prior treatment with more than a total of 3 therapies that include biologic DMARDs or
oral synthetic DMARDs (such as tofacinitib, bariciti


Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis RA

Intervention(s)

Drug: Placebo

Drug: AMG 592

Primary Outcome(s)

ACR 20 [Time Frame: Week 12]

Secondary Outcome(s)

Area under the concentration-time curve (AUCtau) of AMG592 [Time Frame: Week 12]

Maximum observed concentration (Cmax) of AMG592 [Time Frame: Week 12]

DAS 28-CRP [Time Frame: Week 12]

DAS28-ESR [Time Frame: Week 12]

ACR 50/70 [Time Frame: Week 12]

Time of maximum observed concentration (Tmax) of AMG592 [Time Frame: Week 12]

Secondary ID(s)

2017-001944-36

20170149

Source(s) of Monetary Support

Please refer to primary and secondary sponsors