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

• Register: EUCTR
• Last refreshed on: 30 April 2018
• Main ID: EUCTR2015-003230-26-DE
• Date of registration: 14/10/2015
• Prospective Registration: Yes
• Primary sponsor: Medivir AB
• Public title: A study comparing the efficacy, safety and tolerability of two doses of MIV-711 with placebo in patients with knee joint osteoarthritis
• Scientific title: A Randomised, Double-blind Placebo-controlled Phase IIa Study to Evaluate Efficacy, Safety and Tolerability of MIV-711 in Knee Joint Osteoarthritis
• Date of first enrolment: 18/12/2015
• Target sample size: 240
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-003230-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Bulgaria, Georgia, Germany, Moldova, Republic of, Romania, United Kingdom

Contacts

• Name: MIV-711 Clinical Study Information
• Affiliation: Medivir AB

• Name: MIV-711 Clinical Study Information
• Affiliation: Medivir AB

Key inclusion & exclusion criteria

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Knee Joint Osteoarthritis
MedDRA version: 20.0 Level: LLT Classification code 10023476 Term: Knee osteoarthritis System Organ Class: 100000004859

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Product Name: MIV-711(HCl)
Product Code: MIV-711, MV076159
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: MIV-711
CAS Number: 1657002-22-6
Current Sponsor code: MIV-711
Other descriptive name: MIV-711(HCL), MV076159(HCL), CK 1509
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: MIV-711(HCl)
Product Code: MIV-711, MV076159
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: MIV-711
CAS Number: 1657002-22-6
Current Sponsor code: MIV-711
Other descriptive name: MIV-711(HCL), MV076159(HCL), CK 1509
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To assess the effect of MIV-711 on target knee average pain over 26 weeks as measured by an 11-point numerical rating scale (1 week recall) in patients with symptomatic and radiographic knee osteoarthritis

Secondary Objective: To assess the effect of MIV-711 on MRI target knee bone area in patients with symptomatic and radiographic knee OA over 26 weeks
The effect of MIV-11 on:
- worst target knee pain (1 week recall)
- average contralateral knee pain (1 week recall)
- constant and intermittent OA pain
- global improvements in knee problem, knee pain and knee function
- knee joint OA symptoms (function, pain, stiffness)
- global disease activity
- quality of life (QOL)
- MRI bone marrow lesion volume
- MRI cartilage thickness loss
- in the semi quantitative MRI Osteoarthritis Knee Score (MOAKS) parameters
- patient reported e-diary daily recall knee joint pain
- patient reported e-diary daily recall analgesics use
- The safety and tolerability of MIV-711
- biomarkers for bone resorption (serum CTX-I) and for cartilage degradation (urine CTX-II) assessment

Primary end point(s): Change from visit 2 (baseline) to visit 8 in NRS average target knee pain score

Timepoint(s) of evaluation of this end point: Throughout the study

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Throughout the study

Secondary end point(s): Efficacy endpoint:
- Change from visit 2 (baseline) to visit 8 in knee joint MRI bone area
- Change from visit 2 (baseline) to visit 8 in NRS worst target knee pain score
- Change from visit 2 (baseline) to visit 8 in NRS average contralateral knee pain score
- Change from visit 2 (baseline) to visit 8 in constant and intermittent OA pain
- Change from visit 2 (baseline) to visit 8 in knee joint OA symptoms; WOMAC (function, pain, stiffness)
- Change from visit 2 (baseline) to visit 8 in global disease activity
- Change from visit 2 (baseline) to visit 8 in global improvements in knee problem, knee pain and knee function
- Change from visit 2 (baseline) to visit 8 in quality of life (QOL)
- Change from visit 2 (baseline) to visit 8 in MRI bone marrow lesion volume
- Change from visit 2 (baseline) to visit 8 in MRI cartilage thickness loss
- Change from visit 2 (baseline) to visit 8 in the semi quantitative MRI Osteoarthritis Knee Score (MOAKS) parameters
- Change from visit 2 (baseline) to visit 8 in patient-reported e-diary daily recall knee joint pain
- Change from visit 2 (baseline) to visit 8 in patient-reported e-diary daily recall analgesics use
- Changes from visit 2 (baseline) to visit 8 in serum biomarkers C-terminal telopeptide of collagen type I (sCTX-I for bone resorption assessment) and urinary C-terminal telopeptide of collagen type II (uCTX-II for cartilage degradation assessment)
Safety endpoints:
- Incidence and severity of adverse events
- Incidence and severity of clinical laboratory abnormalities
- Summary of changes in physical examination compared to baseline by patient
- Mean change from visit 2 (baseline) in vital signs (blood pressure, heart rate and temperature)
- Categorical summary of absolute vital signs and vital sign changes compared to visit 2 (baseline) by patient

Secondary ID(s)

2015-003230-26-GB

MIV-711-201

Source(s) of Monetary Support

Medivir AB