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

NCT00669942 | Completed Phase 1 Results

• 1 other identifier: CAIN457A2101
• Study Type: interventional
• Target: 104
• Locations: 6 countries
• Sites: 24

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.

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (13)

• Percentage of Parts 2 and 3 Participants Who Achieved American College of Rheumatology Response of 20 (ACR20)

  Clinical response to treatment was assessed according to ACR20 criteria. A participant was defined as an ACR20 responder if the following 3 conditions were met: 1) ≥20% improvement in the number of tender joints, 2) ≥20% improvement in the number of swollen joint and 3) ≥20% improvement in three of the following five domains: patient global assessment, physician global assessment, patient pain assessment, health assessment questionnaire (HAQ) and acute phase reactant.

  Day 43

• Pharmacokinetics (PK) of AIN457: Time to Reach the Maximum Concentration After Drug Administration (Tmax) in Part 1 Participants

  Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 29, 36, 43, 57, 71, 85, 99 and 113.

  Day 113

• PK of AIN457: Observed Maximum Serum Concentration Following Drug Administration (Cmax) in Part 1 Participants

  Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  Day 113

• 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

  Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  Day 113

• PK of AIN457: Volume of Distribution During the Terminal Phase Following Intravenous Elimination (Vz) in Part 1 Participants

  Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  Day 113

• PK of AIN457: Systemic Clearance From Serum Following Intravenous Administration (CL) in Part 1 Participants

  Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  Day 113

• PK of AIN457: Terminal Elimination Half-life (T1/2) in Part 1 Participants

  Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  Day 113

• Pharmacokinetics PK of AIN457: Tmax in Parts 2 and 3 Participants

  Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  Day 113

• Pharmacokinetics PK of AIN457: Cmax in Parts 2 and 3 Participants

  Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  Day 113

• Pharmacokinetics PK of AIN457: AUClast and AUCinf in Parts 2 and 3 Participants

  Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  Day 113

• Pharmacokinetics PK of AIN457: Vz in Parts 2 and 3 Participants

  Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  Day 113

• Pharmacokinetics PK of AIN457: CL in Parts 2 and 3 Participants

  Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  Day 113

• Pharmacokinetics PK of AIN457: T1/2 in Parts 2 and 3 Participants

  Serum samples were collected pre-dose and 0.5, 2, 4, 7, 12 and 24 hours post infusion on day 1, and on days 2, 5, 8, 15, 22, 23, 26, 29, 36, 43, 57, 71, 85, 99 and 113. On day 22, samples were collected pre-dose and 0.5, 1, 2, 4, 7 and 24 hours post infusion.

  Day 113

Secondary Outcomes (2)

• Percentage of Parts 2 and 3 Participants Who Achieved ACR50 and ACR70

  Day 43

• Disease Activity Score (DAS28) of Parts 2 and 3 Participants

  Day 43

Study Arms (12)

Part 1 - AIN457A 0.3 mg/kg

EXPERIMENTAL

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

Biological: AIN457

Part 1 - AIN457A 1.0 mg/kg

EXPERIMENTAL

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

Biological: AIN457

Part 1 - AIN457A 3.0 mg/kg

EXPERIMENTAL

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

Biological: AIN457

Part 1 - AIN457A 10 mg/kg

EXPERIMENTAL

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

Biological: AIN457

Part 1 - Placebo

PLACEBO COMPARATOR

Placebo to AIN457A was administered intravenously as a single dose.

Drug: Placebo

Parts 2 and 3 - AIN457A 1.0 mg/kg

EXPERIMENTAL

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.

Biological: AIN457

Parts 2 and 3 - AIN457A 3.0 mg/kg

EXPERIMENTAL

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.

Biological: AIN457

Parts 2 and 3 - AIN457A 10 mg/kg

EXPERIMENTAL

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.

Biological: AIN457

Parts 2 and 3 - Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Part 1 - Healthy Volunteers - AIN457A 3 mg/kg

EXPERIMENTAL

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

Biological: AIN457

Part 1 - Healthy Volunteers - AIN457A 10 mg/kg

EXPERIMENTAL

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

Biological: AIN457

Part 1 - Healthy Volunteers - Placebo

PLACEBO COMPARATOR

Placebo to AIN457A was administered intravenously as a single dose.

Drug: Placebo

Interventions

AIN457 BIOLOGICAL

AIN457A is a fully human recombinant IgG1 antibody that targets and neutralizes IL-17A.

Part 1 - AIN457A 0.3 mg/kg; Part 1 - AIN457A 1.0 mg/kg; Part 1 - AIN457A 10 mg/kg; Part 1 - AIN457A 3.0 mg/kg; Part 1 - Healthy Volunteers - AIN457A 10 mg/kg; Part 1 - Healthy Volunteers - AIN457A 3 mg/kg; Parts 2 and 3 - AIN457A 1.0 mg/kg; Parts 2 and 3 - AIN457A 10 mg/kg; Parts 2 and 3 - AIN457A 3.0 mg/kg

Placebo DRUG

Placebo to AIN457

Part 1 - Healthy Volunteers - Placebo; Part 1 - Placebo; Parts 2 and 3 - Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (24)

Novartis Investigative Site

Anniston, Alabama, 36207-5710, United States

Location

Novartis Investigative Site

Tucson, Arizona, 85724, United States

Location

Novartis Investigative Site

Largo, Florida, 33773, United States

Location

Novartis Investigative Site

Ocala, Florida, 34471, United States

Location

Novartis Investigative Site

Palm Harbor, Florida, 34684, United States

Location

Novartis Investigative Site

Port Orange, Florida, 32127, United States

Location

Novartis Investigative Site

Madisonville, Kentucky, 42431, United States

Location

Novartis Investigative Site

St Louis, Missouri, 63110, United States

Location

Novartis Investigative Site

Omaha, Nebraska, 68131-2197, United States

Location

Novartis Investigative Site

Oklahoma City, Oklahoma, 73103, United States

Location

Novartis Investigative Site

Bend, Oregon, 97701, United States

Location

Novartis Investigative Site

Duncansville, Pennsylvania, 16635, United States

Location

Novartis Investigative Site

Brussels, 1200, Belgium

Location

Novartis Investigative Site

Merksem, 2170, Belgium

Location

Novartis Investigative Site

Bad Nauheim, 61231, Germany

Location

Novartis Investigative Site

Erlangen, 91054, Germany

Location

Novartis Investigative Site

München, 80336, Germany

Location

Novartis Investigative Site

Amsterdam, 1105 AZ, Netherlands

Location

Novartis Investigative Site

Nijmegen, 6525 GA, Netherlands

Location

Novartis Investigative Site

Singapore, Singapore, 119074, Singapore

Location

Novartis Investigative Site

Singapore, Singapore, 529889, Singapore

Location

Novartis Investigative Site

A Coruña, Galicia, 15006, Spain

Location

Novartis Investigative Site

Santiago de Compostela, Galicia, 15706, Spain

Location

Novartis Investigative Site

Guadalajara, 19002, Spain

Location

Related Publications (1)

• 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.

  PMID: 20926833 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

secukinumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

• Novartis

  Novartis investigator site

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2008
• First Posted: May 1, 2008
• Study Start: December 1, 2005
• Primary Completion: November 1, 2008
• Study Completion: November 1, 2008
• Last Updated: March 30, 2015
• Results First Posted: March 30, 2015

Record last verified: 2015-03

Locations

US (12); SG (2); NL (2); DE (3); BE (2); ES (3)