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

NCT00928317 | Terminated Phase 2 DMC

• 1 other identifier: ART621-221
• Study Type: interventional
• Target: 13
• Locations: 8 countries
• Sites: 46

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  12 weeks

• Immunogenicity profile of ART621 as assessed by development of HAHAs.

  16 weeks

• Plasma concentration versus time profile and population PK of ART621 in subjects with RA.

  16 weeks

• Effect of ART621 on immunological parameters and other disease biomarkers.

  12 weeks

Study Arms (4)

ART621 A

EXPERIMENTAL

ART621 0.75mg/kg per week

Drug: ART621

ART621 B

EXPERIMENTAL

ART621 1.5 mg/kg per week

Drug: ART621

ART621 C

EXPERIMENTAL

ART621 3.0mg/kg per week

Drug: ART621

Placebo arm

PLACEBO COMPARATOR

Drug: Placebo

Interventions

ART621 DRUG

3.0mg/kg s.c.

ART621 C

Placebo DRUG

Placebo s.c.

Placebo arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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-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.

Sponsors & Collaborators

• Arana Therapeutics Ltd: lead

Study Sites (46)

Tampa Medical Group P.A.

Tampa, Florida, 33614, United States

Location

Arthritis Center

Springfield, Illinois, 62704, United States

Location

Physician Research Collaboration, LLC

Lincoln, Nebraska, 68516, United States

Location

Westroads Medical Group

Omaha, Nebraska, 68114, United States

Location

Arthritis Northwest, PLLC

Spokane, Washington, 99204, United States

Location

Arthritis Clinic

Racine, Wisconsin, 53142, United States

Location

Instituto Medico Especializado IME

Buenos Aires, BUE, C1405BCH, Argentina

Location

Instituto Medico CER

Quilmes, Bue, B1878DVB, Argentina

Location

ILAIM-CEOM Inst. Latinoamericano de Inv. Medicas

Córdoba, CRD, X5000BNB, Argentina

Location

Sanatorio Parque S.A.

Rosario, SFE, 2000, Argentina

Location

CAICI

Rosario, SFE, S2000PBJ, Argentina

Location

Ctro Polivalente de Asist e Invest Clinica CER

San Juan, SJN, 5400, Argentina

Location

Centro de Investigaciones Reumatológicas

San Miguel de Tucumán, TUC, 4000, Argentina

Location

Centro Medico Privado de Reumatologia

San Miguel de Tucumán, TUC, T4000AXL, Argentina

Location

IMAI Research - Instituto Medico de Asistencia y Investigaci

Calle French, 2673, Argentina

Location

Centro Medico Privado de Reumatologia

San Miguel de Tucumán, Argentina

Location

Lyell McEwin Hospital

Elizabeth Vale, New South Wales, 5112, Australia

Location

Georgetown Arthritis Centre

Sydney, New South Wales, 2298, Australia

Location

Coast Joint Care

Maroochydore, Queensland, 4558, Australia

Location

The Queen Elizabeth Hospital

Woodville, South Australia, 5011, Australia

Location

Revmatologicka ambulance

Bruntál, 79201, Czechia

Location

Nemocnice Jihlava

Jihlava, 58633, Czechia

Location

ARTHROMED s. r. o.

Pardubice, 53002, Czechia

Location

Fakultni nemocnice Plzen

Plzen - Bory, 30599, Czechia

Location

Revmatologicky ustav

Prague, 12850, Czechia

Location

Apollo Hospital Educational and Research Foundation

Hyderabaad, Andh Prad, 500033, India

Location

Nizams Institute of Medical Sciences

Hyderabaad, Andh Prad, 500082, India

Location

Krishna Institute of Medical Sciences

Secunderabad, Andh Prad, 500003, India

Location

King George Hospital

Vishakhapattanam, Andh Prad, 530002, India

Location

St. John's Medical College Hospital

Bangalore, Karna, 560034, India

Location

M.S. Ramaiah Memorial Hospital

Bangalore, Karna, 560054, India

Location

Centre for Rheumatic Diseases

Pune, Mahara, 411001, India

Location

Apollo Hospitals Educational and Research Foundation

Madurai, Tamil Nadu, 625020, India

Location

Sanjay Gandhi Postgraduate Institute

Lucknow, Uttar Prad, 226014, India

Location

K. M. C. Hospital

Mangalore, 575001, India

Location

Putra Medical Centre

Alor Star, Kedah, 05100, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, 50480, Malaysia

Location

Hospital Ipoh

Perak, 30990, Malaysia

Location

Sarawak General Hospital

Sarawak, 93586, Malaysia

Location

C G M Research Trust, The Princess Margaret Hospital

Christchurch, 8002, New Zealand

Location

NZOZ Centrum Osteoporozy i Chorob Kostno-Stawowych

Bialystok, 15-461, Poland

Location

Samodzielny Publiczny ZOZ w Dzialdowie

Działdowo, 13-200, Poland

Location

Nzoz Reumed

Lublin, 20-607, Poland

Location

Medyczne Centrum Hetmanska

Poznan, 60-218, Poland

Location

SPSK nr 1 im. Tadeusza Sokolowskiego PAM

Szczecin, 71-252, Poland

Location

Centrum Medyczne OSTEOMED

Warsaw, 02-341, Poland

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 24, 2009
• First Posted: June 25, 2009
• Study Start: April 1, 2009
• Primary Completion: November 1, 2009
• Study Completion: December 1, 2009
• Last Updated: January 6, 2010

Record last verified: 2010-01

Locations

US (6); PL (6); MY (4); AU (4); NZ (1); IN (10); CZ (5); AR (10)