Rheumatoid ArthritisPhase 2NCT00928317
Dose Ranging Study of ART621 in Subjects Diagnosed With Rheumatoid Arthritis Taking Methotrexate
A Phase 2 study testing ART621 in people with Rheumatoid Arthritis, run by Arana Therapeutics Ltd at 46 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- ART621
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 46 sitesin 8 countries
- Study dates
- Apr 2009to Dec 2009
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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
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- 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-TNFα therapy or subjects who have had to stop anti-TNFα therapy for safety reasons. Subjects who have successfully responded to anti-TNFα 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-TNFα 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.
Trial locations and contacts
46 sites in 8 countries.
46 sites in 8 countries
Argentina10 sites
Instituto Medico Especializado IME
Buenos Aires, BUE, C1405BCH
IMAI Research - Instituto Medico de Asistencia y Investigaci
Calle French, 2673
ILAIM-CEOM Inst. Latinoamericano de Inv. Medicas
Córdoba, CRD, X5000BNB
Instituto Medico CER
Quilmes, Bue, B1878DVB
Sanatorio Parque S.A.
Rosario, SFE, 2000
CAICI
Rosario, SFE, S2000PBJ
Ctro Polivalente de Asist e Invest Clinica CER
San Juan, SJN, 5400
Centro de Investigaciones Reumatológicas
San Miguel de Tucumán, TUC, 4000
Centro Medico Privado de Reumatologia
San Miguel de Tucumán, TUC, T4000AXL
Centro Medico Privado de Reumatologia
San Miguel de Tucumán
India10 sites
St. John's Medical College Hospital
Bangalore, Karna, 560034
M.S. Ramaiah Memorial Hospital
Bangalore, Karna, 560054
Apollo Hospital Educational and Research Foundation
Hyderabaad, Andh Prad, 500033
Nizams Institute of Medical Sciences
Hyderabaad, Andh Prad, 500082
Sanjay Gandhi Postgraduate Institute
Lucknow, Uttar Prad, 226014
Apollo Hospitals Educational and Research Foundation
Madurai, Tamil Nadu, 625020
K. M. C. Hospital
Mangalore, 575001
Centre for Rheumatic Diseases
Pune, Mahara, 411001
Krishna Institute of Medical Sciences
Secunderabad, Andh Prad, 500003
King George Hospital
Vishakhapattanam, Andh Prad, 530002
United States6 sites
Physician Research Collaboration, LLC
Lincoln, Nebraska, 68516
Westroads Medical Group
Omaha, Nebraska, 68114
Arthritis Clinic
Racine, Wisconsin, 53142
Arthritis Northwest, PLLC
Spokane, Washington, 99204
Arthritis Center
Springfield, Illinois, 62704
Tampa Medical Group P.A.
Tampa, Florida, 33614
Poland6 sites
NZOZ Centrum Osteoporozy i Chorob Kostno-Stawowych
Bialystok, 15-461
Samodzielny Publiczny ZOZ w Dzialdowie
Działdowo, 13-200
Nzoz Reumed
Lublin, 20-607
Medyczne Centrum Hetmanska
Poznan, 60-218
SPSK nr 1 im. Tadeusza Sokolowskiego PAM
Szczecin, 71-252
Centrum Medyczne OSTEOMED
Warsaw, 02-341
Czechia5 sites
Revmatologicka ambulance
Bruntál, 79201
Nemocnice Jihlava
Jihlava, 58633
ARTHROMED s. r. o.
Pardubice, 53002
Fakultni nemocnice Plzen
Plzen - Bory, 30599
Revmatologicky ustav
Prague, 12850
Australia4 sites
Lyell McEwin Hospital
Elizabeth Vale, New South Wales, 5112
Coast Joint Care
Maroochydore, Queensland, 4558
Georgetown Arthritis Centre
Sydney, New South Wales, 2298
The Queen Elizabeth Hospital
Woodville, South Australia, 5011
Malaysia4 sites
Putra Medical Centre
Alor Star, Kedah, 05100
University Malaya Medical Centre
Kuala Lumpur, 50480
Hospital Ipoh
Perak, 30990
Sarawak General Hospital
Sarawak, 93586
New Zealand1 site
C G M Research Trust, The Princess Margaret Hospital
Christchurch, 8002
About this study
Official 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
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.
Read the detailed description
Despite being effective in approximately 60% of subjects, there are limitations to existing anti-TNF therapies especially in relation to immunogenicity, safety and administration. In addition, due to their high molecular weight, currently marketed products are largely confined to the blood stream.
ART621 is an anti-TNF molecule that contains 2 identical domain "antibodies" that have the binding activity of a full antibody but with a substantially smaller molecular size. The molecular weight of approximately half that of full size antibodies is predicted to, a) have improved tissue penetration and, b) to be less immunogenic than full size antibodies.
This clinical trial is designed to assess the safety, efficacy, tolerability, immunogenicity and pharmacokinetics of ART621 when administered with an intravenous loading dose followed by subcutaneous administration every week.
- Conditions
- Rheumatoid Arthritis
- Being tested
- ART621, Placebo
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ART621Drug
3.0mg/kg s.c.
ART621Drug
1.5mg/kg s.c.
ART621Drug
0.75mg/kg s.c.
PlaceboDrug
Placebo s.c.
| Study group | Role | What they receive |
|---|---|---|
| ART621 A | Experimental | ART621 0.75mg/kg per week Receives: Drug: ART621 |
| ART621 B | Experimental | ART621 1.5 mg/kg per week Receives: Drug: ART621 |
| ART621 C | Experimental | ART621 3.0mg/kg per week Receives: Drug: ART621 |
| Placebo arm | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Secondary outcomes (4)
Dose-response relationship of ART621 against the signs and symptoms of moderate to severe RA as assessed by additional efficacy, safety and QoL parameters.
Measured: 12 weeks
Immunogenicity profile of ART621 as assessed by development of HAHAs.
Measured: 16 weeks
Plasma concentration versus time profile and population PK of ART621 in subjects with RA.
Measured: 16 weeks
Effect of ART621 on immunological parameters and other disease biomarkers.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2009 (estimated)
- Study startApr 2009
- Primary completionNov 2009
- Study completionDec 2009
Why it stopped: Corporate re-prioritization
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- 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
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Arana Therapeutics Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00928317
- Sponsor's protocol ID
- ART621-221
- Status last verified
- Jan 2010
- First submitted
- 24 Jun 2009
- Last updated
- 6 Jan 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT00928317
- Acronym / sponsor ID
- ART621-221
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Corporate re-prioritization
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Arana Therapeutics LtdIndustry (pharma, biotech, devices)
- Study start
- Apr 2009
- Primary completion
- Nov 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 25 Jun 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Despite being effective in approximately 60% of subjects, there are limitations to existing anti-TNF therapies especially in relation to immunogenicity, safety and administration. In addition, due to their high molecular weight, currently marketed products are largely confined to the blood stream.
ART621 is an anti-TNF molecule that contains 2 identical domain "antibodies" that have the binding activity of a full antibody but with a substantially smaller molecular size. The molecular weight of approximately half that of full size antibodies is predicted to, a) have improved tissue penetration and, b) to be less immunogenic than full size antibodies.
This clinical trial is designed to assess the safety, efficacy, tolerability, immunogenicity and pharmacokinetics of ART621 when administered with an intravenous loading dose followed by subcutaneous administration every week.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| ART621 A | Experimental | Drug: ART621ART621 0.75mg/kg per week |
| ART621 B | Experimental | Drug: ART621ART621 1.5 mg/kg per week |
| ART621 C | Experimental | Drug: ART621ART621 3.0mg/kg per week |
| Placebo arm | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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.
Key exclusion criteria (33 listed)
- Pregnant, nursing, or planning a pregnancy (both men and women) within 9 months of enrolment.
- Subjects weighing > 100 kgs.
- Screening laboratory tests:
- 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-TNFα therapy or subjects who have had to stop anti-TNFα therapy for safety reasons. Subjects who have successfully responded to anti-TNFα 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-TNFα therapy study are eligible if they are confirmed to have received placebo.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ART6213.0mg/kg s.c. | Drug | ART621 C |
| ART6211.5mg/kg s.c. | Drug | ART621 B |
| ART6210.75mg/kg s.c. | Drug | ART621 A |
| PlaceboPlacebo s.c. | Drug | Placebo arm |
Primary outcome
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
4 secondary outcomes
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
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
Effect of ART621 on immunological parameters and other disease biomarkers.
Time frame: 12 weeks
Results and safety
The study was stopped early (reason given: Corporate re-prioritization). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2010.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
46 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ART621 in people with Rheumatoid Arthritis, run by Arana Therapeutics Ltd at 46 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 6 Jan 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 46 sites in Argentina, India, United States, Poland, Czechia and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Corporate re-prioritization). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2010.