Dose Ranging Study of ART621 in Subjects Diagnosed With Rheumatoid Arthritis Taking Methotrexate

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00928317
• Date of registration: 24/06/2009
• Prospective Registration: No
• Primary sponsor: Arana Therapeutics Ltd
• Public title: Dose Ranging Study of ART621 in Subjects Diagnosed With Rheumatoid Arthritis Taking Methotrexate
• Scientific title: Multi-Centre Randomised Double-Blind Pbo-Controlled Dose-Ranging Study to Evaluate the Safety, Tolerability, Efficacy, PK and Immunogenicity of Multiple Doses of ART621 for 3 Months in Patients With Rheumatoid Arthritis Taking Methotrexate
• Date of first enrolment: April 2009
• Target sample size: 13
• Recruitment status: Terminated
• URL: http://clinicaltrials.gov/show/NCT00928317
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Argentina, Australia, Czech Republic, India, Malaysia, New Zealand, Poland, United States

Key inclusion & exclusion criteria

Inclusion Criteria:

- Provision of a valid written informed consent.

- Male or female subjects = 18 and = 80 years old.

- Women of childbearing potential, or men of fathering potential, must be using
adequate (in the investigator's opinion) birth control measures (e.g. abstinence,
oral contraceptives, intrauterine device, barrier method with spermicide, or surgical
sterilisation) during the study. Female subjects of childbearing potential must test
negative for pregnancy prior to enrolling in the study. Post menopausal (cessation
of menses for more than 2 years) women are eligible for this study.

- Diagnosis of RA according to the revised (1987) American College of Rheumatology
criteria for at least 6 months and no longer than 3 years prior to screening.

- Meet ACR functional class criteria I, II or III.

- Have active RA at the time of screening and at baseline, defined as = 6 swollen
joints and = 6 tender joints (from 68 joint count) together with at least 2 of the
following 3 criteria:

- CRP level = 1.5 mg/dl;

- ESR by Westergren method = 28 mm in the first hour; or

- morning stiffness = 45 minutes.

- At least one of the following should be present at screening:

- documented history or current presence of positive rheumatoid factor;

- presence of serum anti-CCP antibodies; or

- screening radiographic erosion

- Have been tolerating concomitant methotrexate (oral or subcutaneous) for at least 3
months prior to screening and on a stable dose between 10-25 mg per week for at least
6 weeks prior to the first study dose. The route of administration must also be
stable. Use of methotrexate dose of 25-50 mg every 2 weeks is also acceptable.
(Other DMARDs taken concomitantly with methotrexate are not allowed. Those subjects
concomitantly receiving additional DMARDs with methotrexate may enter the study by
stopping the additional DMARD at least 4 weeks prior to first study dose).

- If using the following medication, the subject must be on a stable dose for the 4
weeks prior to the first study dose and maintain that dose throughout the study:

- oral corticosteroids, equivalent to = 10 mg of prednisone/day.

- one nonsteroidal anti-inflammatory drug (NSAID).

- 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) or fibrates
(see Section 7.1 for acceptable doses).

- Does not have active or latent TB according to eligibility assessment and screening
rules (see Section 8.3.1).

- Is willing and able to comply with study visits and other protocol requirements.

Exclusion Criteria:

- Pregnant, nursing, or planning a pregnancy (both men and women) within 9 months of
enrolment.

- Subjects weighing > 100 kgs.

- Screening laboratory tests:

- hemoglobin = 8.0 gm/dl

- white blood cells = 3.0 x103 cells/µl

- neutrophils = 1.5 x 103 cells/µl

- platelets =100 x 103 cells/µl

- serum transaminase level (AST and ALT) = 2 times upper limit of normal (ULN)

- serum creatinine = 0.15 mmol/l

- Subjects with diagnosis of juvenile arthritis or other inflammatory or autoimmune
diseases that might confound the evaluations of benefit from ART621 such as
ankylosing spondylitis, systemic lupus erythematosus and Lyme disease.

- Subjects who have previously failed to respond to any oral or injectable anti-TNFa
therapy or subjects who have had to stop anti-TNFa therapy for safety reasons.
Subjects who have successfully responded to anti-TNFa therapy in the past (but
discontinued for reasons other than safety or lack of efficacy) > 6 months prior to
study day one may enrol. Patients who have participated in a previous anti-TNFa
therapy study are eligible if they are confirmed to have received placebo.

- Subjects who have previously received the following anti-rheumatic drugs:
interleukin-1 receptor antagonist [anakinra], rituximab, anti-CD4 antibody,
abatacept, thalidomide, p38 MAP kinase inhibitor and other agents (other than those
listed in Section 7.3).

- Subjects who have undergone plasmapheresis within 6 months prior to randomisation.

- Have received intraarticular, intramuscular, or intravenous corticosteroids,
including intramuscular adrenocorticotropic hormone, during the 4 weeks prior to the
first study dose, or non-stable doses of oral steroids.

- Subjects with a history of any clinically significant adverse reaction to murine or
chimeric proteins, including serious allergic reactions.

- Subjects with Felty's syndrome or a history of Felty's syndrome.

- Subjects who have received or are expecting to receive any live virus or bacterial
vaccinations within 1 month before first study dose, during the study, or up to 3
months after the study dose.

- Subjects with a history of, presence of, or at high risk of serious infection
including:

- history of active TB, or positive Mantoux test or QuantiFERON Gold test or chest
x-ray suggestive of active or healed TB or positive contact history with a
subject with active TB within the past 3 months. If subjects have a positive
Mantoux test but a negative QuantiFERON Gold test, they may be enrolled.

- a serious infection during the 3 months prior study entry (hospitalised or
received IV antibiotics for an infection).

- chronic or recurrent infectious disease.

- systemic fungal infections

- opportunistic infection within 3 months prior to screening (refer to 1993 CDC
Classification System for HIV Infection).

- subjects known, or suspected, to be infected with HIV, hepatitis B, or hepatitis
C.

- subjects with planned joint replacement surgery or a history of infected joint
prosthesis or who have received antibiotics for a suspected infection of a joint
prosthesis if that prosthesis has not been removed or replaced.

- Subjects with a known history of demyelinating diseases such as multiple sclerosis or
optic neuritis.

- Subjects with evidence of severe, progressive, or uncontrolled renal, hepatic,
hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic,
psychiatric, or cerebral disease.

- Concurrent CHF, including medically controlled, asymptomatic CHF or ECG findings
suggestive of CHF.

- Subjects recei


Age minimum: 18 Years
Age maximum: 80 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis

Intervention(s)

Drug: Placebo

Drug: ART621

Primary Outcome(s)

Efficacy of ART621 on the signs and symptoms of moderate to severe RA in subjects concomitantly taking methotrexate as assessed by the proportion of subjects achieving an ACR20 response. [Time Frame: 12 weeks]

Secondary Outcome(s)

Effect of ART621 on immunological parameters and other disease biomarkers. [Time Frame: 12 weeks]

Immunogenicity profile of ART621 as assessed by development of HAHAs. [Time Frame: 16 weeks]

Plasma concentration versus time profile and population PK of ART621 in subjects with RA. [Time Frame: 16 weeks]

Dose-response relationship of ART621 against the signs and symptoms of moderate to severe RA as assessed by additional efficacy, safety and QoL parameters. [Time Frame: 12 weeks]

Secondary ID(s)

ART621-221

Source(s) of Monetary Support

Please refer to primary and secondary sponsors