A study comparing the efficacy, safety and tolerability of two doses of MIV-711 with placebo in patients with knee joint osteoarthritis

Phase 1

• Conditions: Knee Joint Osteoarthritis; MedDRA version: 19.0 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2015-003230-26-GB
• Lead Sponsor: Medivir AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-10-09
• Study Completion: 2017-05-23
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 244

Inclusion Criteria

1. Current average knee pain, defined as pain in either knee, within 1 week before Visit 1, for which the patient gives a severity score of =4, <10 on a 0-10 NRS.
2. Inclusive of 40-80 years old.
3. Diagnosis of primary knee osteoarthritis, based upon the following:
- Fulfilling the American College of Rheumatology Clinical and Radiographic (ACR) criteria for OA defined as knee pain for most days of the prior month and at least one of the following three factors: age >50 years, morning stiffness of less than 30 minutes and knee crepitus on motion.
- X-ray evidence within the last 12 months for Kellgren and Lawrence (K-L) classification grade 2 or 3.
4. Female patients must be non-pregnant, non-lactating and of non-childbearing potential either as naturally (spontaneously) post-menopausal or due to hysterectomy and/or bilateral oophorectomy/salpingo-oophorectomy (as determined by patient medical history). Naturally (spontaneously) post-menopausal is defined as being amenorrhoic for 12 months without an alternative medical cause and with a screening follicle stimulating hormone indicating post-menopausal state.
5. Male patients should avoid fathering a child by either of the following methods:
- True sexual abstinence: meaning that heterosexual abstinence is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence such as that based on calendar, ovulation, symptothermal, post-ovulation methods, declaration of abstinence for the duration of a trial, or withdrawal/coitus interruptus are not acceptable methods of contraception).
- Willingness to use two effective means of contraception with their partner from the time of first IMP administration until 3 months after the last dose of IMP. Two or more of the following methods are acceptable and must include at least one barrier method: i) Surgical sterilisation (i.e., bilateral tubal ligation for female partners; vasectomy for male), ii) placement of an intrauterine device or intrauterine system, iii) hormonal contraception (implantable, patch, oral), iv) barrier methods including condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. Male patients who have been sterilised are required to use one barrier method of contraception (condom).
6. The patient’s usual analgesic regimen (in case of use) should remain the same for 4 weeks prior to the signature of the informed consent form.
7. Needs to be able to communicate well with the investigators and staff.
8. Able to comply with the requirements of the study procedures and provide written informed consent prior to any study related procedures.
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 120
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120

Exclusion Criteria

1. The presence of any inflammatory arthritis (e.g., gout, reactive arthritis, rheumatoid arthritis, psoriatic arthritis, seronegative spondylarthropathy) or any underlying condition, other than OA, that may result in abnormal cartilage and bone metabolism.
2. Any generalised pain condition that may interfere with the evaluation of the target knee pain (e.g., fibromyalgia) as judged by the investigator.
3. A history of cancer within the previous 5 years (except for cutaneous basal-cell or squamous-cell cancer resolved by excision and cancer in situ which are allowed).
4. Ongoing or a history of atrial fibrillation.
5. Currently receiving medication that affects cartilage or bone metabolism (hormone replacement therapy taken for more than 6 months is allowed).
6. Current or recurrent disease that could affect the action, absorption or disposition of MIV-711, or could affect clinical assessments or clinical laboratory assessments.
7. Any clinically severe or significant uncontrolled concurrent illness, which, in the opinion of the Investigator, would impair ability to give informed consent or take part in or complete this clinical study.
8. Known or suspected intolerance or hypersensitivity to the investigational product, closely related compounds, or any of the stated ingredients.
9. A positive human immunodeficiency virus (HIV) antibody screen, a positive Hepatitis B surface antigen (HBsAg) screen, and/ or a positive Hepatitis C virus (HCV) antibody screen. A positive anti-HBc test in conjunction with a negative anti-HBs test.
10. History of alcohol or other substance abuse within the last year.
11. Use of an investigational product within 30 days prior to receiving the first dose of investigational product or active enrolment in another drug or vaccine clinical study.
12. Significant target knee injury or surgery within the 6 months preceding enrolment in the study.
13. A history of partial or complete joint replacement surgery in the target knee at any time, listed for knee surgery, or anticipating knee surgery during the study period.
14. Any factor which, in the opinion of the investigator, would jeopardise the evaluation or safety of the patient or be associated with poor adherence to the clinical study protocol (e.g., inability to complete study diary, poor tolerability of venipuncture or lack of adequate venous access for required blood sampling during the study period).
15. Use of intra-articular hyaluronic acid in the target knee within the 3 months preceding enrolment in the study.
16. Use of intra-articular, intra-muscular or oral corticosteroids in the 2 months preceding enrolment.
17. Commencement of non-pharmacological OA interventions within two months preceding enrolment.
18. Vulnerable patients, e.g., patients kept in detention, soldiers, and employees of the sponsor or the contract Research Organisation (CRO) with direct involvement in the proposed study or other studies under the direction of the investigator or the CRO, as well as family members of the employees or the investigator.
19. Patients with contra-indication to MRI of the knee.

Study & Design

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