A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Multiple Subcutaneous Injections of ABT-981 in Patients With Osteoarthritis of the Knee

Study Overview
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Brief Summary
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To assess the safety, tolerability and pharmacokinetics of ABT-981 in patients with osteoarthritis of the knee.

Detailed Description
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This is a phase 1, randomized, double-blind, placebo-controlled, multiple ascending dose study. Thirty-six patients with osteoarthritis of the knee will be selected to participate. Patients will be randomized to receive either ABT-981 or placebo. ABT-981 or placebo will be administered as subcutaneous (under the skin) injections in four dosing groups. Subjects will be administered subcutaneous injections of ABT-981 for up to 8 weeks.

Official Title
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A Randomized, Double-Blind, Placebo Controlled Study in Patients With Osteoarthritis of the Knee to Evaluate the Safety, Tolerability and Pharmacokinetics of Multiple Ascending Doses of ABT-981

Conditions
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Osteoarthritis

Intervention / Treatment
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* Biological: ABT-981
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male or female, 40 to 70 years of age, inclusive. History of symptomatic osteoarthritis (OA) of the knee joint for at least 3 months, with typical Osteoarthritis (OA) symptoms Radiographic Osteoarthritis (OA) of Kellgren-Lawrence (K-L) grade 1, 2 or 3 Patients assessment of Osteoarthritis (OA) pain intensity of the study joint is between 40 and 80 on the 0 - 100 mm VAS scale Other than Osteoarthritis (OA) of the study joint, patient should be in general good health Exclusion Criteria: Radiographic OA of Kellgren-Lawrence grade 4 or chronic opioid user due to severe knee OA History of allergic reaction or significant sensitivity to any constituents of the study drug and acetominophen or history of anaphylactic reaction to any agent Significant trauma or surgery to the study joint within the last year or arthroscopy within 6 months, or, scheduled for major surgery to the study joint Diagnosis of rheumatoid arthritis, other autoimmune disorders or any arthritis other than Osteoarthritis (OA) of the knee. Any uncontrolled medical illness including unstable treatment or therapy.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1<br>Randomized 7 drug/2 placebo by group | Biological: ABT-981<br>* Injection<br>Biological: Placebo<br>* Placebo Injection<br>|
| Experimental: Group 2<br>Randomized 7 drug/2 placebo by group | Biological: ABT-981<br>* Injection<br>Biological: Placebo<br>* Placebo Injection<br>|
| Experimental: Group 3<br>Randomized 7 drug/2 placebo by group | Biological: ABT-981<br>* Injection<br>Biological: Placebo<br>* Placebo Injection<br>|
| Experimental: Group 4<br>Randomized 7 drug/2 placebo by group | Biological: ABT-981<br>* Injection<br>Biological: Placebo<br>* Placebo Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events | Collect all adverse events at each visit | From date of first dose of ABT-981 until 70 days after the last dose of ABT-981 | 
| Physical Exam including vital signs | Blood pressure, heart rate and body temperature | From date of first dose of ABT-981 until 70 days after last dose of ABT-981 | 
| Clinical Lab Testing | Hematology, Chemistry, and Urinalysis | From date of first dose of ABT-981 until 70 days after the last dose of ABT-981 | 
| Change from Baseline in Electrocardiogram (ECG) | ECGs done in triplicate | Prior to dose and 8 hours post dose on each day of dosing | 
| Maximum observed serum concentration (Cmax) of ABT-981 | Cmax | Prior to first dose up to 70 days after the last dose of ABT-981 | 
| Time to Cmax (Tmax) of ABT-981 | Time to Cmax | Prior to first dose up to 70 days after the last dose of ABT-981 | 
| The area under the time curve (AUC) of ABT-981 | AUC | Prior to first dose up until 70 days after the last dose of ABT-981 | 
| The terminal phase elimination rate constant and the terminal elimination half-life (t1/2) of ABT-981 | The terminal phase elimination rate constant and the terminal elimination half-life (t1/2) of ABT-981 | Prior to the last dose up to 70 days after the last dose of ABT-981 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of anti-drug anti-bodies (ADA) of ABT-981 | Measurement of ADA | Prior to each dose and up until 70 days after the last dose of ABT-981 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunogenicity, Safety, Tolerability, Osteoarthritis, Pharmacokinetics