Clinical trial NCT00048321: ISIS 104838, an Inhibitor of Tumor Necrosis Factor, for Active Rheumatoid Arthritis
Official title: ISIS 104838-CS7, A Double-Blind, Placebo-Controlled, Randomized Trial of the Safety, Efficacy and Pharmacokinetic Profile of ISIS 104838 (TNF-alpha Antisense Oligonucleotide) Subcutaneous Injections in Active Rheumatoid Arthritis Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2002-10-31
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

Brief summary: ISIS 104838 is an antisense oligonucleotide drug that reduces the production of a specific protein called tumor necrosis factor (TNF-alpha), a substance that contributes to joint pain and swelling in rheumatoid arthritis. ISIS 104838 works by blocking TNF-alpha messenger RNA, the "instruction" molecule that is required for the production of TNF-alpha protein. This trial will assess the safety and efficacy of ISIS 1048383 by subcutaneous injection, administered by 3 different dosing regimens for 3 months, versus placebo. Approximately 160 TNF-alpha inhibitor-naïve rheumatoid arthritis patients will be evaluated at 32 sites in the U.S. and Canada.


Eligibility criteria: Inclusion Criteria

1. Age \>/= 18 years.
2. Rheumatoid arthritis for \>/= 6 months.
3. Active disease as defined by \>/= 6 swollen and \>/= 9 tender joints, AND an abnormal C-reactive protein or Westergren Erythrocyte Sedimentation Rate lab test, OR Morning Stiffness \>/= 1 hour.
4. Use of at least one DMARD, and ability to discontinue any current DMARD.

Exclusion Criteria

1. Onset of rheumatoid arthritis before the 16th birthday.
2. Wheelchair or bed-bound functional level.
3. No previous infliximab or etanercept treatment, or investigational therapy (not placebo) with other TNF-alpha inhibitors.
4. Prednisone \> 10 mg per day or more than one nonsteroidal anti-inflammatory drug.
5. Patients with an active infection, a history of tuberculosis, multiple sclerosis, other poorly controlled medical illness, or a malignancy within the last 5 years.
6. Patients who require intravenous heparin therapy or with a history of a bleeding problem.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Paradise Valley
country: United States
state: Arizona
city: Los Angeles
country: United States
state: California
city: Rancho Cucamonga
country: United States
state: California
city: Fort Lauderdale
country: United States
state: Florida
city: Palm Harbor
country: United States
state: Florida
city: Sarasota
country: United States
state: Florida
city: Tampa
country: United States
state: Florida
city: Decatur
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Wichita
country: United States
state: Kansas
city: Louisville
country: United States
state: Kentucky
city: Greenbelt
country: United States
state: Maryland
city: Fall River
country: United States
state: Massachusetts
city: Lansing
country: United States
state: Michigan
city: Saint Louis
country: United States
state: Missouri
city: Albuquerque
country: United States
state: New Mexico
city: Mayfield
country: United States
state: Ohio
city: Duncansville
country: United States
state: Pennsylvania
city: Willow Grove
country: United States
state: Pennsylvania
city: Amarillo
country: United States
state: Texas
city: Carrollton
country: United States
state: Texas
city: Dallas
country: United States
state: Texas
city: Lubbock
country: United States
state: Texas
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Calgary
country: Canada
state: Alberta
city: Edmonton
country: Canada
state: Alberta
city: Victoria
country: Canada
state: British Columbia
city: Ottawa
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
Study officials:
References:
citation: Burel SA, Machemer T, Baker BF, Kwoh TJ, Paz S, Younis H, Henry SP. Early-Stage Identification and Avoidance of Antisense Oligonucleotides Causing Species-Specific Inflammatory Responses in Human Volunteer Peripheral Blood Mononuclear Cells. Nucleic Acid Ther. 2022 Dec;32(6):457-472. doi: 10.1089/nat.2022.0033. Epub 2022 Aug 17.