E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adult male and female patients with mild to moderate, symptomatic, radiographic and inflammatory osteoarthritis of the knee |
|
E.1.1.1 | Medical condition in easily understood language |
Mild to moderate knee osteoarthritis |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031161 |
E.1.2 | Term | Osteoarthritis |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of ABT-981 on OA knee pain using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at Week 16 and synovitis/effusion volume of the index knee using quantitative measures and semi-quantitative MRI scoring at Week 26 in patients with knee osteoarthritis. |
|
E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
1. PK substudy
2. Synovial Fluid substudy
3. DCE-MRI substudy |
|
E.3 | Principal inclusion criteria |
1.Subject must have radiographic evidence of knee osteoarthritis in the medial compartment of the index knee with Kellgren-Lawrence Grade 2 or 3 (with minimum 2 mm joint space width) during Screening as evaluated by a qualified central imaging reader. Prior radiographs taken no more than 3 months before Study Day 1 with Synaflexer™ can be submitted for centralized eligibility reading.
2. Subject must have either constant or intermittent index knee pain at least 14 days (regardless the intensity)over the past 30 days at the initial screening visit. The intensity of index knee pain is between 4 and 8 , inclusive, at the initial Screening Visit and Study Day 1 (as recorded on question 1 of the Index Knee Pain Intensity Questionnaire.
3.Subject has one or more clinical signs and symptoms of active inflammation in the index knee as defined by (but not limited to) localized pain, joint stiffness, swelling and effusion during Screening and Study Day 1.
4.Presence of synovitis in the index knee confirmed by ultrasound or MRI during Screening.
5.Subject discontinued analgesics, non-steroidal anti-inflammatory drugs (NSAIDS) and nutraceuticals (e.g., glucosamine, chondroitin sulfate, shark cartilage, diacerein, soy extract). The washout period will be at least 5 half-lives of the longest acting analgesic used, or 48 hours, whichever is longer prior to first dose of study drug. |
|
E.4 | Principal exclusion criteria |
1.History of major allergic reaction or significant sensitivity to any constituents of the study drug, or history of anaphylactic reaction to any agent (e.g., food products or bee stings) or history of a major reaction to any Immunoglobulin G (IgG-)containing product.
2.Significant trauma or surgery to the index knee within the last year or arthroscopy of the index knee within 6 months of the Initial Screening Visit.
3.Kellgren-Lawrence Grade 1 or 4 in the index knee.
4.Severe knee malalignment, either greater than 4.0° in varus; or greater than 8.0° in valgus angulation in the index knee.
5.Diagnosis of one or more of the following:
a.Inflammatory arthritis such as rheumatoid arthritis, autoimmune disorder, seronegative spondyloarthropathy, gout, or pseudogout (defined as acute episodic attacks of swollen , painful joints in a subject with X-Ray chondrocalcinosis or CPPD crystals);
b.Other chronic painful syndromes (such as Paget's disease and fibromyalgia) and clinically significant non-articular musculoskeletal pain that could interfere with assessment of pain at the index knee.
6. History or evidence of active tuberculosis (TB)
7. Any uncontrolled medical illness or unstable treatment ot therapy. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The change from baseline to week 16 in OA knee pain using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and from baseline to week 26 in synovitis/effusion volume of the index knee using quantitative and semi-quantitative MRI scoring |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
● To evaluate the safety and tolerability of ABT-981 in patients with knee OA.
● To evaluate the effect of ABT-981 on physical function scores of the index knee at Weeks 16, 26 and 52 using WOMAC.
● To evaluate the effect of ABT-981 on index knee pain scores at Weeks 26 and 52 using WOMAC.
● To evaluate the effect of ABT-981 in reduction of bone marrow lesions (BML) of the index knee MRI at Weeks 26 and 52 using semi quantitative measurements (WORMS).
● To evaluate the effect of ABT-981 on index knee resting pain at Weeks 16, 26 and 52 using the Intermittent and Constant Osteoarthritis Pain (ICOAP) score.
● To evaluate the effect of ABT-981 on index knee resting pain at Weeks 16, 26 and 52 using the 11-point NRS scale (NRS-11).
● To evaluate the effect of ABT-981 on Patient Global Assessment of Arthritis at Weeks 16, 26 and 52.
● To evaluate the effect of ABT-981 on the preservation of cartilage volume/thickness of the index knee using MRI at Weeks 26 and 52.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Denmark |
France |
Germany |
Italy |
Mexico |
Netherlands |
Spain |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |