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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00928317




Registration number
NCT00928317
Ethics application status
Date submitted
24/06/2009
Date registered
25/06/2009
Date last updated
6/01/2010

Titles & IDs
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
Secondary ID [1] 0 0
ART621-221
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ART621
Treatment: Drugs - ART621
Treatment: Drugs - ART621
Treatment: Drugs - Placebo

Experimental: ART621 A - ART621 0.75mg/kg per week

Experimental: ART621 B - ART621 1.5 mg/kg per week

Experimental: ART621 C - ART621 3.0mg/kg per week

Placebo Comparator: Placebo arm -


Treatment: Drugs: ART621
3.0mg/kg s.c.

Treatment: Drugs: ART621
1.5mg/kg s.c.

Treatment: Drugs: ART621
0.75mg/kg s.c.

Treatment: Drugs: Placebo
Placebo s.c.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
12 weeks
Secondary outcome [1] 0 0
Dose-response relationship of ART621 against the signs and symptoms of moderate to severe RA as assessed by additional efficacy, safety and QoL parameters.
Timepoint [1] 0 0
12 weeks
Secondary outcome [2] 0 0
Immunogenicity profile of ART621 as assessed by development of HAHAs.
Timepoint [2] 0 0
16 weeks
Secondary outcome [3] 0 0
Plasma concentration versus time profile and population PK of ART621 in subjects with RA.
Timepoint [3] 0 0
16 weeks
Secondary outcome [4] 0 0
Effect of ART621 on immunological parameters and other disease biomarkers.
Timepoint [4] 0 0
12 weeks

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 receiving cytotoxic drugs including cyclophosphamide, cyclosporine, or
alkylating agents within 6 months prior to first study dose.

- Known history or evidence of malignancy, lymphoproliferative or neoplastic disease
with the exception of successfully treated basal or squamous cell carcinoma of the
skin or cervical intraepithelial neoplasia.

- Subjects who have undergone organ transplant (with exception of a corneal transplant
more than 3 months prior to screening).

- Subjects previously enrolled in this study, currently participating in another
investigational study or treated with any investigational drug within the previous 3
months or within 5 half-lives, whichever is greater, prior to first study dose.

- Any other clinically significant disease or disorder or factors such as substance
abuse which in the opinion of the investigator make the subject ineligible for
participation in this study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/04/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2009
Sample size
Target
Accrual to date
Final
13
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA
Recruitment hospital [1] 0 0
Lyell McEwin Hospital - Elizabeth Vale
Recruitment hospital [2] 0 0
Georgetown Arthritis Centre - Sydney
Recruitment hospital [3] 0 0
Coast Joint Care - Maroochydore
Recruitment hospital [4] 0 0
The Queen Elizabeth Hospital - Woodville
Recruitment postcode(s) [1] 0 0
5112 - Elizabeth Vale
Recruitment postcode(s) [2] 0 0
2298 - Sydney
Recruitment postcode(s) [3] 0 0
4558 - Maroochydore
Recruitment postcode(s) [4] 0 0
5011 - Woodville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Nebraska
Country [4] 0 0
United States of America
State/province [4] 0 0
Washington
Country [5] 0 0
United States of America
State/province [5] 0 0
Wisconsin
Country [6] 0 0
Argentina
State/province [6] 0 0
BUE
Country [7] 0 0
Argentina
State/province [7] 0 0
Bue
Country [8] 0 0
Argentina
State/province [8] 0 0
CRD
Country [9] 0 0
Argentina
State/province [9] 0 0
SFE
Country [10] 0 0
Argentina
State/province [10] 0 0
SJN
Country [11] 0 0
Argentina
State/province [11] 0 0
TUC
Country [12] 0 0
Argentina
State/province [12] 0 0
Calle French
Country [13] 0 0
Argentina
State/province [13] 0 0
San Miguel de Tucuman
Country [14] 0 0
Czech Republic
State/province [14] 0 0
Bruntal
Country [15] 0 0
Czech Republic
State/province [15] 0 0
Jihlava
Country [16] 0 0
Czech Republic
State/province [16] 0 0
Pardubice
Country [17] 0 0
Czech Republic
State/province [17] 0 0
Plzen - Bory
Country [18] 0 0
Czech Republic
State/province [18] 0 0
Praha 2
Country [19] 0 0
India
State/province [19] 0 0
Andh Prad
Country [20] 0 0
India
State/province [20] 0 0
Karna
Country [21] 0 0
India
State/province [21] 0 0
Mahara
Country [22] 0 0
India
State/province [22] 0 0
Tamilnadu
Country [23] 0 0
India
State/province [23] 0 0
Uttar Prad
Country [24] 0 0
India
State/province [24] 0 0
Mangalore
Country [25] 0 0
Malaysia
State/province [25] 0 0
Kedah
Country [26] 0 0
Malaysia
State/province [26] 0 0
Kuala Lumpur
Country [27] 0 0
Malaysia
State/province [27] 0 0
Perak
Country [28] 0 0
Malaysia
State/province [28] 0 0
Sarawak
Country [29] 0 0
New Zealand
State/province [29] 0 0
Christchurch
Country [30] 0 0
Poland
State/province [30] 0 0
Bialystok
Country [31] 0 0
Poland
State/province [31] 0 0
Dzialdowo
Country [32] 0 0
Poland
State/province [32] 0 0
Lublin
Country [33] 0 0
Poland
State/province [33] 0 0
Poznan
Country [34] 0 0
Poland
State/province [34] 0 0
Szczecin
Country [35] 0 0
Poland
State/province [35] 0 0
Warszawa

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Arana Therapeutics Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this clinical trial is to assess the safety, efficacy, tolerability,
immunogenicity and pharmacokinetics of 3 dose levels of ART621 in the treatment of rheumatoid
arthritis.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00928317
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00928317