Clinical trial NCT00669942: Double Blind, Placebo-controlled, Study of the Safety, Tolerability and Pharmacokinetics of AIN457 in Rheumatoid Arthritis Patients
Official title: A Randomized, Double Blind, Placebo-controlled, Dose Escalation Study of the Safety, Tolerability and Pharmacokinetics of AIN457 in Rheumatoid Arthritis Patients With Pharmacodynamics Assessed in an Expanded Cohort at the Maximum Tolerated Dose
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid Arthritis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2008-05-01
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Parts 2 and 3 Participants Who Achieved American College of Rheumatology Response of 20 (ACR20)
timeFrame: Day 43
measure: Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1 Participants
timeFrame: Day 113
measure: PK of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) in Part 1 Participants
timeFrame: Day 113
measure: PK of AIN457: Area Under the Serum Concentration-time Cure From Time Zero to the Time of Last Quantifiable Concentration (AUClast), Area Under the Serum Concentration-time Curve From Time Zero to (AUCinf) in Part 1 Participants
timeFrame: Day 113
measure: PK of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) in Part 1 Participants
timeFrame: Day 113
measure: PK of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) in Part 1 Participants
timeFrame: Day 113
measure: PK of AIN457: Terminal Elimination Half-life (T1/2) in Part 1 Participants
timeFrame: Day 113
measure: Pharmacokinetics PK of AIN457: Tmax in Parts 2 and 3 Participants
timeFrame: Day 113
measure: Pharmacokinetics PK of AIN457: Cmax in Parts 2 and 3 Participants
timeFrame: Day 113
measure: Pharmacokinetics PK of AIN457: AUClast and AUCinf in Parts 2 and 3 Participants
timeFrame: Day 113
measure: Pharmacokinetics PK of AIN457: Vz in Parts 2 and 3 Participants
timeFrame: Day 113
measure: Pharmacokinetics PK of AIN457: CL in Parts 2 and 3 Participants
timeFrame: Day 113
measure: Pharmacokinetics PK of AIN457: T1/2 in Parts 2 and 3 Participants
timeFrame: Day 113
Secondary outcomes:
measure: Percentage of Parts 2 and 3 Participants Who Achieved ACR50 and ACR70
timeFrame: Day 43
measure: Disease Activity Score (DAS28) of Parts 2 and 3 Participants
timeFrame: Day 43
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Tucson
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Largo
country: United States
facility: Novartis Investigative Site
state: Florida
city: Ocala
country: United States
facility: Novartis Investigative Site
state: Florida
city: Palm Harbor
country: United States
facility: Novartis Investigative Site
state: Florida
city: Port Orange
country: United States
facility: Novartis Investigative Site
state: Florida
city: Madisonville
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: St. Louis
country: United States
facility: Novartis Investigative Site
state: Missouri
city: Omaha
country: United States
facility: Novartis Investigative Site
state: Nebraska
city: Oklahoma City
country: United States
facility: Novartis Investigative Site
state: Oklahoma
city: Bend
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Duncansville
country: United States
facility: Novartis Investigative Site
state: Pennsylvania
city: Bruxelles
country: Belgium
facility: Novartis Investigative Site
city: Merksem
country: Belgium
facility: Novartis Investigative Site
city: Bad Nauheim
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Amsterdam
country: Netherlands
facility: Novartis Investigative Site
city: Nijmegen
country: Netherlands
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Santiago de Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Guadalajara
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
affiliation: Novartis investigator site
name: Novartis
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hueber W, Patel DD, Dryja T, Wright AM, Koroleva I, Bruin G, Antoni C, Draelos Z, Gold MH; Psoriasis Study Group; Durez P, Tak PP, Gomez-Reino JJ; Rheumatoid Arthritis Study Group; Foster CS, Kim RY, Samson CM, Falk NS, Chu DS, Callanan D, Nguyen QD; Uveitis Study Group; Rose K, Haider A, Di Padova F. Effects of AIN457, a fully human antibody to interleukin-17A, on psoriasis, rheumatoid arthritis, and uveitis. Sci Transl Med. 2010 Oct 6;2(52):52ra72. doi: 10.1126/scitranslmed.3001107.