Double Blind, Placebo-controlled, Study of the Safety, Tolerability and Pharmacokinetics of AIN457 in Rheumatoid Arthritis Patients

Novartis

Status and phase: Completed; Phase 2; Phase 1

Conditions: Rheumatoid Arthritis

Treatments: Drug: Placebo; Biological: AIN457

Study type: Interventional

Funder types: Industry

Identifiers

NCT00669942

CAIN457A2101

Details and patient eligibility

About

Evaluate the safety, tolerability and pharmacokinetics of AIN457 when administered as a single dose (intravenous infusion) in patients with active rheumatoid arthritis in combination with a stable dose of methotrexate. And to compare efficacy on the dose groups.

Enrollment: 104 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male and female patients with active rheumatoid arthritis in combination with a stable dose of methotrexate aged 18-75 years may participate in this trial.
• Post menopausal or surgically sterile female patients are allowed. Women of child-bearing potential may participate if they are on a stable dose of methotrexate and if they are practicing effective contraception for at least 6 months prior to screening, willing to use 2 forms of contraception, including at least 1 barrier method during the study and for at least 2 months following the completion/discontinuation of the study.
• Patients must have a diagnosis of active rheumatoid arthritis of stages I, II or III (ACR 1987 revised classification for criteria for RA). Disease duration of at least 6 months prior to randomization is essential;

Exclusion criteria

• Current treatment with anti-TNF-α or anti IL-1 therapy (or other biological therapy).
• Patients with congestive heart failure or poorly controlled diabetes mellitus (HbA1c value ≥10%).
• Presence of any major chronic inflammatory autoimmune diseases like psoriasis, psoriatic arthritis, spondyloarthropathy, inflammatory bowel disease or SLE that can mimic rheumatoid arthritis diagnosis or that can interfere with efficacy evaluation in the study.
• History of renal trauma, glomerulonephritis or patient with one kidney.
• Pregnant or breastfeeding women will be excluded.
• A positive tuberculin skin test.

Other protocol-defined inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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104 participants in 12 patient groups, including a placebo group

Part 1 - AIN457A 0.3 mg/kg

Experimental group

Description:

AIN457A 0.3 mg/kg was administered intravenously as a single dose.

Treatment:

Biological: AIN457

Part 1 - AIN457A 1.0 mg/kg

Experimental group

Description:

AIN457A 1.0 mg/kg was administered intravenously as a single dose.

Treatment:

Biological: AIN457

Part 1 - AIN457A 3.0 mg/kg

Experimental group

Description:

AIN457A 3.0 mg/kg was administered intravenously as a single dose.

Treatment:

Biological: AIN457

Part 1 - AIN457A 10 mg/kg

Experimental group

Description:

AIN457A 10.0 mg/kg was administered intravenously as a single dose.

Treatment:

Biological: AIN457

Part 1 - Placebo

Placebo Comparator group

Description:

Placebo to AIN457A was administered intravenously as a single dose.

Treatment:

Drug: Placebo

Parts 2 and 3 - AIN457A 1.0 mg/kg

Experimental group

Description:

AIN457A 1.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.

Treatment:

Biological: AIN457

Parts 2 and 3 - AIN457A 3.0 mg/kg

Experimental group

Description:

AIN457A 3.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.

Treatment:

Biological: AIN457

Parts 2 and 3 - AIN457A 10 mg/kg

Experimental group

Description:

AIN457A 10.0 mg/kg was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.

Treatment:

Biological: AIN457

Parts 2 and 3 - Placebo

Placebo Comparator group

Description:

Placebo to AIN457A was administered intravenously as 2 doses 21 days apart, i.e. the first dose on day 1 and the second dose on day 22.

Treatment:

Drug: Placebo

Part 1 - Healthy Volunteers - AIN457A 3 mg/kg

Experimental group

Description:

AIN457A 3.0 mg/kg was administered intravenously as a single dose.

Treatment:

Biological: AIN457

Part 1 - Healthy Volunteers - AIN457A 10 mg/kg

Experimental group

Description:

AIN457A 10 mg/kg was administered intravenously as a single dose.

Treatment:

Biological: AIN457

Part 1 - Healthy Volunteers - Placebo

Placebo Comparator group

Description:

Placebo to AIN457A was administered intravenously as a single dose.

Treatment:

Drug: Placebo