Arthritis, Psoriatic
Conditions
Keywords
Psoriatic Arthritis, Arthritis, Psoriasis, Psoriatic, PsA
Brief summary
hOKT3gamma1 (Ala-Ala) is a man-made antibody that is commonly used to prevent organ rejection. The purpose of this study is to determine whether hOKT3gamma1 (Ala-Ala) is safe and effective in psoriatic arthritis patients who are unable to control their arthritis with methotrexate or azathioprine.
Detailed description
Psoriatic arthritis is a form of inflammatory arthritis that affects approximately 7% of people who have psoriasis. Treatment typically include drugs such as methotrexate, azathioprine, and etanercept, which suppress the immune system in a nonspecific fashion in an attempt to control the immune responses causing the disease. In some severe cases of psoriatic arthritis, these drugs cannot adequately control the disease, often requiring patients to undergo continuous treatment to prevent or combat disease activity. hOKT3gamma1 (Ala-Ala) is a genetically engineered monoclonal antibody directed against the CD3 antigen on T cells. hOKT3gamma1 (Ala-Ala) specifically targets immune cells that are actively involved in destructive immune responses, such as those that cause psoriatic arthritis. In a small pilot study of eight people with psoriatic arthritis who received a 2-week course of hOKT3gamma1 (Ala-Ala), the drug appeared safe and caused no serious side effects. This study will test the safety and efficacy of hOKT3gamma1 (Ala-Ala) in alleviating symptoms in psoriatic arthritis patients. This study will last 2 years. Individuals with psoriatic arthritis who are receiving methotrexate or azathioprine therapy and have active disease are eligible to participate. Participants will be randomly assigned to receive hOKT3gamma1 (Ala-Ala) or placebo. Participants will receive a 5-day treatment with the drug or placebo every month for the first 4 months of the study. There will be 5 study visits over 2 years to assess the safety and effectiveness of hOKT3gamma1 (Ala-Ala) and to evaluate laboratory measures related to the underlying immune problems that cause psoriatic arthritis.
Interventions
DRUGPlacebo
Intravenous dose of placebo given over 5 days of each 28 day cycle
Escalating dose given IV over 5 days (1mg, 2mg, 4mg on days 3-5) of each 28 day cycle
Sponsors
Immune Tolerance Network (ITN)
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of psoriatic arthritis. Participants do not need to have concurrent psoriasis to participate in the study; * Active inflammation in 3 or more joints; * Currently receiving ongoing therapy with methotrexate or azathioprine; and * Willing to use acceptable forms of contraception.
Exclusion criteria
* Active infection with HIV, hepatitis C virus, or hepatitis B virus; * Uncompensated heart failure or a recent myocardial infarction (heart attack) within the 6 months prior to study entry; * Certain other serious illnesses or cancers; * Participation in another clinical trial within the 6 weeks prior to study entry; or * Pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Who Received at Least Two Cycles of Treatment and Who Showed Predefined Levels of Improvement in Primary Efficacy Parameter at Six Months | 6 Months | Participants who improve by at least 1 unit from baseline in either the physician or participant global assessment and have at least 30% improvement from baseline in either tender or swollen joint scores\[1\] at 6 months from start of treatment and received at least 2 cycles of treatment 1. The tender and swollen joint scores assess 68 and 66 joints, respectively, with each joint rated from 0 to 3. Total scores range from 0-204 for tenderness and 0-198 for swelling, with higher scores indicating more severe symptoms\[2\]. 2. Ref: Clegg DO et al. Arthritis Rheum. 1996; 39(12):2013-20. |
Countries
United States
Participant flow
Recruitment details
Two centers in the United States enrolled four participants between March 2006 and September 2006 who had psoriatic arthritis with three or more active joints despite ongoing therapy with methotrexate or azathioprine
Pre-assignment details
At screening visit, participants underwent procedures to establish inclusion/exclusion criteria and then sign the informed consent form
Participants by arm
| Arm | Count |
|---|---|
| hOKT3gamma1 (Ala-Ala) Escalating dose of hOKT3gamma1 (Ala-Ala) given intravenously over 5 days of each 28 day cycle | 3 |
| Placebo Intravenous dose of placebo given over 5 days of each 28 day cycle | 1 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | hOKT3gamma1 (Ala-Ala) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 4 Participants | 3 Participants |
| Age, Continuous | 54 years STANDARD_DEVIATION 0 | 46.3 years STANDARD_DEVIATION 9.4 | 43.7 years STANDARD_DEVIATION 9.6 |
| Region of Enrollment United States | 1 participants | 4 participants | 3 participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 3 | 1 / 1 |
| serious Total, serious adverse events | 1 / 3 | 0 / 1 |
Outcome results
Primary
Proportion of Participants Who Received at Least Two Cycles of Treatment and Who Showed Predefined Levels of Improvement in Primary Efficacy Parameter at Six Months
Participants who improve by at least 1 unit from baseline in either the physician or participant global assessment and have at least 30% improvement from baseline in either tender or swollen joint scores\[1\] at 6 months from start of treatment and received at least 2 cycles of treatment 1. The tender and swollen joint scores assess 68 and 66 joints, respectively, with each joint rated from 0 to 3. Total scores range from 0-204 for tenderness and 0-198 for swelling, with higher scores indicating more severe symptoms\[2\]. 2. Ref: Clegg DO et al. Arthritis Rheum. 1996; 39(12):2013-20.
Time frame: 6 Months
Population: Intent-to-treat