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    Summary
    EudraCT Number:2021-006540-28
    Sponsor's Protocol Code Number:LEVI-04-21-02
    National Competent Authority:Czechia - SUKL
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-04-11
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedCzechia - SUKL
    A.2EudraCT number2021-006540-28
    A.3Full title of the trial
    A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy and Safety of LEVI-04 in Patients with Osteoarthritis of the Knee
    Randomizovaná, dvojitě zaslepená, placebem kontrolovaná studie fáze 2a k posouzení účinnosti a bezpečnosti přípravku LEVI-04 u pacientů s osteoratrózou kolena
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy and Safety of LEVI-04 in Patients with Osteoarthritis of the Knee
    Randomizovaná, dvojitě zaslepená, placebem kontrolovaná studie fáze 2a k posouzení účinnosti a bezpečnosti přípravku LEVI-04 u pacientů s osteoratrózou kolena
    A.4.1Sponsor's protocol code numberLEVI-04-21-02
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorLevicept Ltd.
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportLevicept Ltd.
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNBCD A/S
    B.5.2Functional name of contact pointRegulatory Affairs
    B.5.3 Address:
    B.5.3.1Street AddressTelefonvej 8D, 2.
    B.5.3.2Town/ citySøborg
    B.5.3.3Post code2860
    B.5.3.4CountryDenmark
    B.5.4Telephone number4573707908
    B.5.6E-mailregulatory@nbcd.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.2Product code LEVI-04
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSolution for infusion (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeLEVI-04
    D.3.9.3Other descriptive nameLEVI-04
    D.3.9.4EV Substance CodeSUB187894
    D.3.10 Strength
    D.3.10.1Concentration unit g/ml gram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravascular use (Noncurrent)
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Osteoarthritis of the knee
    E.1.1.1Medical condition in easily understood language
    Knee OA
    E.1.1.2Therapeutic area Diseases [C] - Musculoskeletal Diseases [C05]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10023476
    E.1.2Term Knee osteoarthritis
    E.1.2System Organ Class 10028395 - Musculoskeletal and connective tissue disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of LEVI-04 (multiple doses) compared to placebo in reducing pain due to knee OA.
    E.2.2Secondary objectives of the trial
    1) To evaluate the efficacy of LEVI-04 (multiple doses) compared to placebo in improving physical function.
    2) To evaluate the efficacy of LEVI-04 (multiple doses) compared to placebo in improving joint stiffness.
    3) To evaluate the efficacy of LEVI-04 (multiple doses) compared to placebo in Patient Global Assessment (PGA).
    4) To evaluate the proportion of responders based on various levels of reduced pain in participants receiving LEVI-04 (multiple doses) compared to placebo.
    5) To evaluate rescue medication use in the LEVI-04 group (multiple doses) compared to placebo.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Signed Informed Consent form (ICF).
    2. Male or female participants between ≥40 and ≤80 years of age.
    3. BMI ≤40 kg/m2.
    4. The ability to utilize the eDiary device provided by study sites.
    5. History of knee pain on most days for at least 3 months prior to Screening
    6. Confirmation of OA of the knee
    a. Radiographs of both knees with a Posterior-Anterior, Fixed-flexion view taken during the Screening Period.
    b. American College of Rheumatology (ACR) clinical and radiographic diagnostic criteria.
    7. Evidence of knee OA with a KL grade ≥2, determined through central reading.
    8. Target Knee must have a score of ≥20 out of 50 on the WOMAC pain subscale during Screening and at Randomization
    9. The Baseline (NRS) Pain score will be derived from the last seven days of the Diary Run-In Period and must meet following criteria:
    a. Completion of Average Daily (NRS) Pain score on at least 6 of the 7 days.
    b. Mean Average Daily (NRS) Pain score must be ≥4.0 and ≤9.0
    c. Mean Average Daily (NRS) Pain variability must be ≤1.5
    10. If female, not of childbearing potential defined as post-menopausal for at least 1 year, or surgically sterile (bilateral tubal ligation, bilateral oophorectomy, or hysterectomy), or practicing an agreed upon highly effective method of birth control throughout the study period.
    11. If male and sexually active with partner of childbearing potential, willing to agree to practice a highly effective method of contraception from Visit 2 and at least 3 months after Visit 11 (week 20).
    12. Willing to withdraw from any medication for Osteoarthritis including, but not limited to, Opioids (including semisynthetic opioids), Non-Steroidal Anti-inflammatories (NSAIDs), COX-2 inhibitors, Topical medication, and Serotonin and Noradrenaline Reuptake Inhibitors (SNRIs
    e.g Duloxetine).
    13. Participant agrees to take only the allowed Rescue Medications from the start of the Diary Run-In Period through study completion (maximum 4000 mg paracetamol per day).
    E.4Principal exclusion criteria
    1. Presence of OA of other major joints (including nontarget knee) that could interfere with assessment of pain due to OA of the target knee, in the opinion of the investigator.
    2. Current comorbid condition, other than OA, affecting target knee or systemic illness known to be significantly associated with arthritis or joint pathology affecting any joint, including endocrinopathies or autoimmune disease with significant joint involvement (e.g.,Rheumatoid Arthritis); Seronegative Spondyloarthropathies (e.g. Ankylosing Spondylitis, Psoriasis arthritis, Reactive arthritis)
    3. Pathological conditions significantly affecting joint and bone health, in the opinion of the Investigator should be excluded (including following findings on x-rays and/or MRI): known presence of Rapidly Progressive Osteoarthritis, osteonecrosis (including avascular necrosis), subchondral insufficiency fractures (major joint), fractures or stress reactions with radiographic signs of ongoing healing processes (including osteoporotic and pathological fractures) (major joint), excessive malalignment of the knee (anatomical axis angle greater than 10 degrees) (Target knee only), complete tear of the posterior meniscal root (either knee), large
    or extensive subchondral cysts (either knee), anserine or patellar bursitis (Target knee only), significant articular bone loss, articular bone fragmentation or collapse, primary or metastatic tumor, joint infection, paget's disease, osteochondritis dissecans
    4. Hip dislocation and congenital hip dysplasia with degenerative joint disease should be excluded
    5. History of gout, or pseudogout, unless on hypouricemic therapy (including allopurinol) and no episodes within the last 12 months
    6. Presence of neuropathic pain deemed likely to interfere with trial endpoints, complex regional pain syndrome, or chronic widespread pain syndromes e.g., fibromyalgia
    7. History of significant trauma or surgery (excluding injection therapies and arthroscopy) to a knee, hip, or shoulder within the previous 1 year or previous target knee alloplasty
    8. Planned major surgery or other major invasive procedures while participating in the study
    9. Surgery or stent placement for coronary artery disease in the six months prior to screening
    10. Nondiagnostic arthroscopy performed on the target knee joint within 180 days prior to Screening; or diagnostic arthroscopy performed on the target knee joint within 90 days prior to Screening
    11. Intraarticular injection therapies to the target knee joint within 12 weeks prior to Screening, or to any non-target major joint within 6 weeks prior to Screening
    12. Participants likely to be deemed unfit for joint replacement surgery due to concomitant illness, in the investigator opinion
    13. Opioid use, including Tramadol, of 4 or more instances per week over the month prior to Screening
    14. Known history of hypersensitivity to monoclonal antibodies
    15. Presence of any medical condition or unstable health status that, in the judgment of the investigator, might adversely impact the safety of the participant or efficacy results of the trial
    16. Medical history and/or clinical findings (including ECG) of cardiac disease that in the opinion of the investigator are considered of clinical significance, including but not limited to established ischemic heart disease, peripheral arterial disease and /or cerebrovascular disease (unstable angina, myocardial infarction, cardiovascular thrombotic events, transient ischemic attacks, and stroke are considered clinically significant if time of event occurred within six months prior to
    screening)
    17. Active malignancy or history of malignancy within the past 5 years, with exception of resected and cured basal cell carcinoma and squamous cell carcinoma of the skin
    18. Clinically significant abnormal laboratory parameter(s) and/or ECG parameter(s) during Screening, that, in the judgment of the Investigator, would preclude the participant from participation in this study
    19. Participation in other studies involving investigational drug(s) within 30 days (or 90 days for biologics) prior to screening
    20. History of Carpal Tunnel Syndrome with signs or symptoms within one year of Screening or a Boston Carpal Tunnel questionnaire (Symptom Severity Scale mean score ≥3)
    21. Total score on Number of Symptoms (Column Q1a) on the SAS >3
    22. Pregnant or breast feeding
    23. Previously received any form of anti-Nerve Growth Factor
    24. Requires walker or wheelchair for mobility (walking stick permitted)
    25. Active or historic substance abuse within one year of Screening in the opinion of the
    Investigator
    26. Medical history within 5 years of Screening that involves suicidal ideation, suicide attempt, or increased risk of suicide as assessed by the Investigator.
    27. Presence of any contraindication to MRI, including partial or total joint replacements that are expected to interfere with the quality of the imaging
    E.5 End points
    E.5.1Primary end point(s)
    Change in WOMAC Pain subscale from Randomization (Visit 3) to Visit 10 (week 17)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Week 17
    E.5.2Secondary end point(s)
    1) Change in WOMAC Pain subscale from Randomization (Visit 3) to Visit 6 (week 5).
    2) Change in WOMAC Physical function subscale from Randomization (Visit 3) to Visit 6 (week 5) and Visit 10 (week 17).
    3) Change in WOMAC Stiffness subscale from Randomization (Visit 3) to Visit 6 (week 5) and Visit 10 (week 17).
    4) Change in StEPP from Randomization (Visit 3) to Visit 6 (week 5) and Visit 10 (week 17).
    5) Change in PGA from Visit 6 (week 5) to Visit 10 (week 17).
    6) Proportion of participants achieving 30% and 50% reduction in WOMAC Pain subscale at week 5 and week 17 using a cumulative distribution function.
    7) Rescue Medication usage during the trial.
    8) Change in average weekly NRS score from Randomization (Visit 3) to Visit 6 (week 5) and Visit 10 (week 17).
    9) Area under the curve of Average Daily NRS pain from Randomization (Visit 3) to Visit 11 (week 20).
    E.5.2.1Timepoint(s) of evaluation of this end point
    1) From rand. to week 5.
    2) From rand. to week 5 and week 17.
    3) From rand. to week 5 and week 17.
    4) From rand. to week 5 and week 17.
    5) From week 5 to week 17.
    6) Week 5 and week 17.
    7) End of trial.
    8) From rand. to week 5 and week 17.
    9) From rand. to week 20.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Physiological saline (0.9% sodium chloride injection), sourced locally by the clinical site
    E.8.2.4Number of treatment arms in the trial4
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA10
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Moldova, Republic of
    Hong Kong
    Czechia
    Denmark
    Poland
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days15
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months8
    E.8.9.2In all countries concerned by the trial days15
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 313
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 207
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state150
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 437
    F.4.2.2In the whole clinical trial 520
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Standard of care
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2022-07-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-04-13
    P. End of Trial
    P.End of Trial StatusOngoing
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