A Study to Evaluate Safety and Tolerability of MIV-711 in Patients with Knee Joint Osteoarthritis

• Register: EUCTR
• Last refreshed on: 24 September 2018
• Main ID: EUCTR2016-001096-73-BG
• Date of registration: 08/08/2016
• Prospective Registration: Yes
• Primary sponsor: Medivir AB
• Public title: A Study to Evaluate Safety and Tolerability of MIV-711 in Patients with Knee Joint Osteoarthritis
• Scientific title: An Open-Label, One-Arm Phase II Extension Study to Evaluate Safety and Tolerability of MIV-711 in Patients with Knee Joint Osteoarthritis
• Date of first enrolment: 13/09/2016
• Target sample size: 80
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001096-73
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• 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

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:
Patients must meet all of the following criteria to be eligible for enrolment in this study:
1. Previously enrolled in Study MIV-711-201 including completion of Visit 8 either by
• Receiving MIV-711 200 mg and had non-significant clinical worsening on the primary endpoint as defined by NRS increase of =2
OR by
• Receiving placebo and had a clinically significant worsening on the primary endpoint as defined by NRS increase of =2
The NRS result will be derived using the primary endpoint from Study MIV-711-201: NRS average knee pain in the target knee with 7 days recall: increase from Baseline (Visit 2 of Study MIV-711-201) to Visit 8 of Study MIV-711-201.
2. Female patients must be non-pregnant, non-lactating and of nonchildbearing potential either as naturally(spontaneously) postmenopausal or due to hysterectomy and/or bilateral oophorectomy/salpingo-oophorectomy (as determined by patient medical history). Naturally (spontaneously) post-menopausal is defined as being amenorrhoeic for 12 months without an alternative medical cause and with a Screening follicle stimulating hormone test indicating
post-menopausal state.
3. 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 sterilization (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).
4. The patient's usual analgesic regimen (in case of use) should remain the same as for Visit 8 in Study MIV-711-201 (i.e., Visit 1 in Study MIV- 711-202).
NOTE: If a patient is experiencing increased or decreased pain and requires an increase or a decrease in the dose of analgesics, or an occasional change of analgesics medication during his/her participation in the study, then this will be allowed and should be properly documented in the patient file and the CRF.
5. Needs to be able to communicate well with the investigators and staff.
6. 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 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion criteria:
Patients will be excluded from enrolment in this study if they meet any of the following 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. Ongoing or a history of atrial fibrillation.
4. Currently receiving medication that affects cartilage or bone metabolism (other than study drug; hormone replacement therapy taken for more than 6 months is allowed).
5. Current or recurrent disease that could affect the action, absorption or disposition of MIV-711, or could affect clinical assessments or clinical laboratory assessments.
6. 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.
7. Any medical condition, AE, clinical or laboratory finding from Study MIV-711-201 that, in the opinion of the Investigator, would preclude inclusion in the present clinical study.
8. Known or suspected intolerance or hypersensitivity to the investigational medicinal product, closely related compounds, or any of the stated ingredients.
9. History of alcohol or other substance abuse within the last year.
10. Use of an investigational product other than MIV-711 during participation in Study MIV-711-201 and /or active enrolment in another drug or vaccine clinical study.
11. Significant target knee injury or surgery during participation in Study MIV-711-201.
12. 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.
13. 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 venepuncture or lack of adequate venous access for required blood sampling during the study period).
14. Use of intra-articular hyaluronic acid in the target knee during participation in Study MIV-711-201.
15. Use of intra-articular, intra-muscular or oral corticosteroids during participation in Study MIV-711-201.
16. Commencement of non-pharmacological OA interventions during participation in Study MIV-711-201.
17. 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.
18. Lack of MRI of the knee from Visit 8 in Study MIV-711-201 due to special circumstances, such as claustrophobia or difficulties to fit the knee coil.
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 Join Osteoarthritis
MedDRA version: 19.0 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
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: None
CAS Number: 1657002-22-6
Current Sponsor code: MIV-711
Other descriptive name: MIV-711 (HCl), MV076159 (HCl), CK1509
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: Primary Objective Study Population A -
To assess the safety and tolerability of 200 mg MIV-711 q.d. over 52 (26+26) weeks in patients with symptomatic and radiographic knee osteoarthritis.

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

Primary end point(s): Primary Endpoint (Study Population A)
The primary objective is to study the safety and tolerability of MIV-711 in OA patients who have received treatment for up to 52 (26+26) weeks.
Safety endpoints:
• Incidence and severity of AEs
• Incidence and severity of clinical laboratory abnormalities
• Physical examination findings by patient
• Incidence and severity of ECG abnormalities
• Mean change from Baseline (Visit 2 of Study MIV-711-201) in vital signs (blood pressure, heart rate, temperature) and oxygen saturation
• Categorical summary of observed vital signs and vital sign changes compared to Baseline (Visit 2 of Study MIV-711-201), by patient

Secondary Objective: Secondary Objectives Study Population A
To assess, in patients with symptomatic and radiographic knee OA, over 52 (26+26) weeks:
• The effect of MIV-711 on MRI cartilage thickness loss
• The effect of MIV-711 on MRI bone marrow lesion volume
• The effect of MIV-711 in the semi quantitative MRI Osteoarthritis Knee Score (MOAKS) parameters
• To assess the effect of MIV-711 on MRI knee joint bone area.

Secondary Objective Study Population B
To assess the effect of 200 mg MIV-711 q.d. on safety and tolerability over 26 weeks in patients with symptomatic and radiographic knee osteoarthritis.

Secondary Outcome(s)

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

Secondary end point(s): Secondary Endpoints (Study Population A)
Bone parameters will be measured from MRIs of the bone area taken at Visit 2 (Enrolment) and Visit 8 of Study MIV-711-201 as well as the MRI of the bone area taken at Visit 5 in Study MIV-711-202.
MRIs will be analysed semi-quantitatively by a central experienced musculoskeletal radiologist using the MOAKS and quantitatively using statistical shape modelling (SSM, Imorphics Ltd) for the features below.
MOAKS scoring will be used to assess the following features:
- Bone marrow lesions (BMLs) and cysts: 15 sub-regions graded for BML (including ill-defined lesions and cysts) size in regard to the total volume of the sub-region occupied by BML(s). Grade 0=none, grade 1<33% of sub-regional volume, grade 2=33–66% of sub-regional volume and grade 3>66% of sub-regional volume.
- Articular cartilage: 14 articular cartilage regions graded for size of any cartilage loss (including partial and full thickness loss) as a % of surface area as related to the size of each individual region surface and % of loss in this sub-region that is full-thickness loss.
- Osteophytes: 12 sites scored for presence and size of osteophytes. Grade 0=none; Grade 1=small; Grade 2= medium; Grade 3= large.
Bone shape modelling of MRI will be used to assess:
- Mean cartilage thickness (mm) for each of the anterior, posterior and central regions, with areas denuded of cartilage included as having zero thickness
- Bone marrow lesion volume (mm3) by anatomical region: medial and lateral femorotibial region of femur, medial and lateral patellofemoral region of femur, medial and lateral tibia, and patella
- Bone area (mm2) for anatomical regions: lateral and medial femur (patellofemoral); lateral and medial femur (femorotibial); lateral and medial patella, lateral and medial tibial condyle
- Bone shape by distance along an OA shape vector for femur, tibia and patella
- Index bone area/cartilage thickness.

Secondary Endpoints (Study Population B)
These are the same as the primary endpoints for Study Population A

Secondary ID(s)

MIV-711-202

Source(s) of Monetary Support

Medivir AB