A study to determine the safety, tolerability and efficacy of AMAP102 compared to placebo in patients with osteoarthritis

• Conditions: Osteoarthritis; MedDRA version: 16.1Level: LLTClassification code 10023476Term: Knee osteoarthritisSystem Organ Class: 100000004859; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]; MedDRA version: 16.1Level: LLTClassification code 10019115Term: Hand osteoarthritisSystem Organ Class: 100000004859

• Registration Number: EUCTR2012-001769-34-SE
• Lead Sponsor: AnaMar AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-07-18
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Male or female outpatients aged = 50 years.
2. Male or female outpatients with a body mass index of 18 to 30 kg/m2 and a minimum weight of 50 kg.
3. Patients with a clinical diagnosis of unilateral or bilateral knee OA based on clinical and radiographic criteria. Patients should fulfill the validated criteria for the classification of primary OA, published by the American College of Rheumatology (ACR):
• The ACR Classification Criteria (1986) for clinical and radiographic OA of the knee are:
- Knee pain.
- Osteophytes
- And one of the following:
o Age = 50 years.
o Stiffness of < 30 minutes upon rising in the morning.
o Crepitus.
4. Patients taking non-steroidal anti-inflammatory drugs (NSAIDs) or paracetamol at a dose suggested by the European Medicines Agency-approved over-the-counter/prescription labelling on a regular basis (approximately 20 of the past 30 days) prior to the screening visit and with a history of knee pain treatment response with NSAID or paracetamol use.
5. Patients with mild to moderate OA of the knee at the screening visit (Visit 1). Mild to moderate OA of the knee is defined using the following criteria:
•Mild: mild symptoms (no limitations of normal activities).
•Moderate: moderate symptoms (limitation of some normal activities).
•Severe: severe symptoms (inability to carry out most normal activities).
•Extreme: very severe symptoms (inability to carry out all normal activities).
6. Patients with arthritis ‘flare’ in the target knee within 12 days of withdrawing from NSAID or paracetamol. Flare, by definition, must meet the criteria described below and the patient should be randomised as soon as these criteria are met:
•Minimum score of 5 or greater on the 11-item NRS for the patient’s overall pain intensity during activity in the target knee for the last 24 hours on 2 consecutive days, taken from patient’s diary and a score of 5 or greater in the target knee at Visit 2 (baseline).
•Increase of at least 2 on the NRS for the patient’s overall pain intensity during activity in the target knee within the last 24 hours when compared with the value obtained at the screening visit (Visit 1).
7. Ability to provide written, personally signed, and dated informed consent to participate in the study, in accordance with the ICH GCP Guideline E6 and applicable regulations, before completing any study related procedures.
8. An understanding, ability, and willingness to fully comply with study procedures and restrictions.
9. The ability to swallow and retain all of the investigational medicinal product.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

1.The patient has primary inflammatory diseases of the joint (e.g.rheumatoid arthritis,psoriatic arthritis,Reiter’s syndrome,arthritis of inflammatory spondyloarthropathy or inflammatory bowel disease, or infectious arthritis).
2.The patient has unstable knees including a history of the knee catching or giving way and/or physical examination evidence of instability (e.g.positive posterior drawer sign,positive Lachman,positive anterior drawer sign,medial or lateral collateral ligament instability,etc).
3.The patient has arthropathies that occur in conjunction with systemic diseases such as chondrocalcinosis,chondromatosis,gout,pseudo gout,haemophilia,or collagen vascular disease.
4.The patient has a chronic pain condition (e.g.somatisation disorders,chronic headache,fibromyalgia,etc).The patient has chronic lower back pain (individual cases should be discussed with the Medical Monitor) that could confound the analgesic response of the study medication.
5.The patient has a history of knee surgery within the past 12 months,arthroscopy within the past 6 months,or is anticipated to undergo knee surgery in next 3 months or general surgery during the time of participation in the study.
6.The patient has advanced joint damage (Kellgren-Lawrence grade 4); or,in the opinion of the investigator,the patient has advanced joint damage assessed without an X-ray.
7.The patient has a history of osteotomies.
8.The patient is using any of the prohibited medications that are listed in Table 3 of the protocol.
9.The patient used opioids (e.g.codeine,propoxyphene,or combinations of these drugs with NSAIDs or paracetamol) for OA pain within 1 month or 5 half-lives of the drug (whichever is longer) prior to the screening visit (Visit 1).
10.The patient received intra-articular injections of sodium hyaluronate agents within 6 months or 5 half lives of the drug (whichever is longer) before the screening visit (Visit 1) or steroids in joints other than the knee or intravenous or intramuscular steroids within 2 months or 5 half-lives of the drug (whichever is longer) before the screening visit (Visit 1).
11.The patient used oral steroids,intra-articular steroids in the knee, or other immunosuppressant medications within 2 months or 5 half-lives of the drug (whichever is longer) before the screening visit (Visit 1).
12.The patient received methotrexate within 30 days before the screening visit (Visit 1).
13.The patient must agree not to take rescue medication (paracetamol) between the screening visit and baseline, and for 24 hours before any clinic visit.
14.The patient has significant renal impairment (defined as a serum creatinine > 2 x upper limit of normal [ULN] or creatinine clearance < 30 mL/min), liver enzymes elevated > 3 x ULN, positive class III/IV angina or uncontrolled congestive heart failure in the opinion of the investigator, significant active hepatic disease, history of malignant neoplastic disease (other than basal cell carcinoma of the skin) within the past 5 years, or a current severe infectious disease with or without fever.
15.The patient is a woman of childbearing potential who has a positive serum pregnancy test or is a nursing mother. The patient is not surgically sterile (by tubal ligation or hysterectomy) or at least 2 years postmenopausal and has not practiced an acceptable form of birth control (defined as the use of an intrauterine device with spermicide, a barrier method with spermicide, condoms with spermicide, subdermal implant,

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy of AMAP102 in patients with pain secondary to osteoarthritis (OA) over 28 days of dosing;Secondary Objective: • To assess the efficacy of AMAP102 in OA patients.<br>• To assess the safety and tolerability of AMAP102 in OA patients.<br>• To measure the plasma concentrations of AMAP102 in OA patients.<br>• To explore the effects of AMAP102 on interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF a), cartilage oligomeric matrix protein (COMP), and serotonin (5-HT) in OA patients<br>;Primary end point(s): Primary Efficacy Endpoint: WOMAC Pain subscale for the target knee.<br>;Timepoint(s) of evaluation of this end point: Primary Efficacy Endpoint: at Visit 2 (Day 1) Visit 3 (Day 7), Visit 4 (Day 14) and Visit 5 (Day 28)