An Open Label, Randomized-controlled Trial to Assess Efficacy Safety of HYALODISC With Physical Exercise Program

Overview

The objective of this study is to determine if one single X-ray-guided intradiscal injection of 8 mg/mL of HYALODISC combined with PEP will be more effective than only physical exercise program in patients with LBP from degenerative disc disease.

Enrolled patients will be randomly assigned to one of the two treatment groups below:

• Group 1: One single X-ray-guided intradiscal injection (25 gauge) of 8 mg/mL of HYALODISC combined with PEP. The investigator will use one syringe for each involved disc, up to a maximum of three discs.
• Group 2: PEP alone. The injection will be administered at V1 baseline (day 0). Any physical activity (e.g. jogging, tennis, weightlifting, prolonged upright position) in the 48 hours following the injection should be avoided.

Both groups (Group 1 and Group 2) will be treated with PEP according to a standardized protocol. Starting one week after the baseline visit (V1), patients will be prescribed of 18 physiotherapy sessions that will take place under supervision of physiotherapist twice a week in the first seven weeks (weeks 2-8) and once a week in the next four weeks (weeks 9-12). Twelve repetitions of each exercise for 3 sets will be performed during PEP session. Moreover, in addition to the 18 sessions performed with supervision of the physiotherapist, all patients will be instructed how to do exercises at home and will be asked to continue these exercises once a week in the first seven weeks (weeks 2-8) and twice a week in the next four weeks (weeks 9-12).

Description

During the inclusion visit (V0) upon signature of the informed consent, eligible subject will be enrolled. At baseline visit (V1) eligible subjects will then randomly assigned to 1 of 2 treatment groups: HYALODISC + PEP (Group 1) or PEP alone (Group 2). At baseline visit (V1) HYALODISC (8 mg/ml) will be administered to group 1. The investigator will use one syringe for each involved disc, up to a maximum of three discs. The maximum volume that could be injected is 1.5 mL for each disc involved.

The PEP session will start for both groups one week after V1. Randomized subjects will follow the instructions during the PEP session, for a total of 18 sessions that will be performed under supervision of physiotherapist twice a week in the first seven weeks (weeks 2-8) and once a week in the next four weeks (weeks 9-12). Twelve repetitions of each exercise for 3 sets will be performed during PEP session. Moreover, all patients will be instructed how to continue these exercises at home, where the execution will be once a week in the first seven weeks (weeks 2-8) and twice a week in the next four weeks (weeks 9-12). Patients in group 2 that still present low back pain score > 6, despite the PEP, at the physical examination at V3 (12 weeks after V1), could be treated with HYALODISC intradiscally. Those patients will be then evaluated at 12 weeks after the treatment (week 24).

Follow-up visits are set at 4, 12 and 24 weeks (V2, V3 and V4)

Eligibility

Inclusion Criteria:

1. Male or female patients aged 18-70 years;
2. Written informed consent;
3. Willing and able to comply with the protocol for the duration of the study;
4. Chronic low back pain for at least 3 months from the screening;
5. Patients with at least one lumbar (L1-S1) black disc (Pfirrmann grade III-V) seen on magnetic resonance imaging (MRI) examination (MRI performed within 4 months from the screening visit);
6. Low back pain score of at least 5 on a 0-10 NRS at screening;
7. Roland-Morris Disability Questionnaire score of at least 9 on the 24-point questionnaire at screening;
8. If female of childbearing potential, must have a negative pregnancy test at screening and agree to use a reliable form of contraception throughout the study*.

        Note: To be considered of non-childbearing potential, females must be surgically sterile or
        postmenopausal for at least 1 year.
        * Highly effective birth control methods include: combined hormonal contraception
        (containing estrogen and progestogen) associated with inhibition of ovulation (oral,
        intravaginal, transdermal); progestogen-only hormonal contraception associated with
        inhibition of ovulation (oral, injectable, implantable); intrauterine device (IUD);
        intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomised
        partner; sexual abstinence..
        Exclusion Criteria:
          1. Cauda equina syndrome;
          2. Active malignancy or tumours as source of symptoms;
          3. Current infection or prior history of spinal infection (e.g., discitis, septic
             arthritis, epidural abscess) or an active systemic infection;
          4. Previous lumbar spine surgery;
          5. Evidence of prior lumbar vertebral body fracture;
          6. Patients with radiculopathy caused by nerve root compression;
          7. Verbiest Syndrome of Lumbar Spine;
          8. Spondylolisthesis (> Grade 1) with or without spondylolysis at the symptomatic
             level(s);
          9. Radiological sacroiliac joint involvement;
         10. Patients with positive response to medial branch block;
         11. Patients that did physical exercise therapy in the last three months before screening;
         12. For patients that need to perform a MRI at the screening visit, contraindications to
             perform the MRI, such as patients carrying cerebral clips or cooling, valvular
             endoprosthesis with metal components, defibrillators, pacemakers or neurostimulant
             devices;
         13. Sacrum-iliac synchondrosis agenesis seen on MRI;
         14. Patients with symptomatic hernia, sciatica or spinal cord injury:
         15. Significant systemic disease, including unstable angina, autoimmune disease,
             rheumatoid arthritis, and muscular dystrophy;
         16. Congenital or acquired coagulopathy or thrombocytopenia; or currently taking
             anticoagulant, antineoplastic, antiplatelet, or thrombocytopenia-inducing medications;
             or undergoing radiation therapy;
         17. Patients with known allergies, hypersensitivity or intolerance to paracetamol and/or
             active or inactive excipients of formulation;
         18. Ongoing or previous participation in another drug or device clinical study within the
             previous 2 months from the screening;
         19. Females known to be pregnant or nursing at time of enrolment or with plans to become
             pregnant within the planned length of follow-up or unwilling to use adequate
             contraception and conduct a pregnancy test at screening;
         20. Patients with suspected or known history of hypersensitivity to hyaluronic acid or to
             hyaluronate preparations or gram-positive bacterial proteins;
         21. Patients unable to provide a valid informed consent or those acting in an emergency
             situation..