PainPhase 2NCT05618782
Clinical Trial to Evaluate the Efficacy and Safety of LEVI-04 in Patients With Osteoarthritis of the Knee
A Phase 2 study testing LEVI-04 in people with Pain and Osteo Arthritis Knee, run by Levicept at 13 sites in 5 countries.
Trial summary
This is a phase 2, randomized, double-blind, placebo-controlled trial of multiple doses and multiple administrations of LEVI-04 for the treatment of pain due to osteoarthritis of the knee. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- Conditions the study is for
- Pain, Osteo Arthritis Knee, Knee Osteoarthritis
- What is being tested?
- LEVI-04
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 518 participants
- Where
- 13 sitesin 5 countries
- Study dates
- 19 Oct 2022to 20 May 2024
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed Informed Consent form (ICF).
- Male or female participants between ≥40 and ≤80 years of age.
- BMI ≤40 kg/m2.
- The ability to utilize the eDiary device provided by study sites.
- History of knee pain on most days for at least 3 months prior to Screening
- Confirmation of OA of the knee
Show all 18Show fewer
- Radiographs of both knees with a Posterior-Anterior, Fixed-flexion view taken during the Screening Period.
- American College of Rheumatology (ACR) clinical and radiographic diagnostic criteria.
- Evidence of knee OA with a KL grade ≥2, determined through central reading.
- Target Knee must have a score of ≥20 out of 50 on the WOMAC pain subscale during Screening and at Randomization
- The Baseline (NRS) Pain score will be derived from the last seven days of the Diary Run-In Period and must meet following criteria:
- Completion of Average Daily (NRS) Pain score on at least 6 of the 7 days.
- Mean Average Daily (NRS) Pain score must be ≥4.0 and ≤9.0
- Mean Average Daily (NRS) Pain variability must be ≤1.5
- 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.
- 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).
- Willing to withdraw from any medication for Osteoarthritis including, but not limited to, Opioids, Non-Steroidal Anti-inflammatories (NSAIDs), COX-2 inhibitors, Topical medication, and Duloxetine.
- 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).
Who cannot join
- Presence of OA of other major joints (including but not limited to nontarget knee) that could interfere with assessment of pain due to OA of the target knee, in the opinion of the investigator.
- Current comorbid condition, other than OA, known to be significantly associated with arthritis or joint pathology, including but not necessarily limited to autoimmune disease with significant joint involvement (e.g., Rheumatoid Arthritis or Paget's disease; Seronegative Spondyloarthropathies (e.g. Ankylosing Spondylitis, Psoriasis arthritis, Reactive arthritis); or other systemic disease involving the target knee (including endocrinopathies).
- The following conditions should be excluded: Known presence of rapidly Progressive Osteoarthritis (RPOA), primary osteonecrosis (including spontaneous osteonecrosis of the knee), subchondral insufficiency fractures (SIF), avascular necrosis, osteoporotic fractures, atrophic OA, excessive malalignment of the knee (anatomical axis angle greater than 10 degrees), pathological fractures, or stress fracture or reaction, vertical tear of the posterior meniscal root, or large or extensive subchondral cysts, or target knee anserine or patellar bursitis of clinical relevance
- Hip dislocation and congenital hip dysplasia with degenerative joint disease should be excluded.
- History of gout with recent (< 6 months) pain flares and uncontrolled uric acid levels. Participants with a history or diagnosis of pseudogout (calcium pyrophosphate dihydrate crystal deposition disease) can enroll if there has not been a flare within 6 months prior to screening and use of NSAIDs is not required for management of this condition.
- Presence of neuropathic pain deemed likely to interfere with trial endpoints, complex regional pain syndrome, or chronic widespread pain syndromes e.g., fibromyalgia.
Show all 27Show fewer
- History of significant trauma (e.g., intra-articular fracture) or surgery (excluding injection therapies and arthroscopy) to a knee, hip, or shoulder within the previous 1 year
- Planned major surgery or other major invasive procedures while participating in the study.
- Surgery or stent placement for coronary artery disease in the six months prior to screening .
- 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.
- Intraarticular injection therapies to the target knee joint within 12 weeks prior to Screening, or to any non-target joint within 6 weeks prior to Screening.
- Participants likely to be deemed unfit for joint replacement surgery due to concomitant illness, in the investigator opinion.
- Opioid use, including Tramadol, of 4 or more instances per week over the month prior to Screening.
- Known history of hypersensitivity to monoclonal antibodies.
- Presence of any medical condition or unstable health status that, in the judgment of the investigator, might adversely impact the safety of the participant.
- Signs and symptoms of significant cardiac disease, 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 in the six months prior to screening)
- 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.
- 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.
- Participation in other studies involving investigational drug(s) within 30 days (or 90 days for biologics) prior to screening.
- History of Carpal Tunnel Syndrome with symptoms within one year of Screening or a Boston Carpal Tunnel Questionnaire (Symptom Severity Scale) mean score ≥3.
- A total Symptom Impact score on the Survey of Autonomic Symptoms ≥3.
- Pregnant or breast feeding.
- Previously received any form of anti-NGF
- Requires walker or wheelchair for mobility (walking stick permitted).
- Active or historic substance abuse within one year of Screening in the opinion of the Investigator.
- Medical history within 5 years of Screening that involves suicidal ideation, suicide attempt, or increased risk of suicide as assessed by the Investigator.
- Presence of any contraindication to MRI
Trial locations and contacts
13 sites in 5 countries.
13 sites in 5 countries
Poland4 sites
NZOZ Bif-Med. s.c.
Bytom
Somed CR
Lodz
Medyczne Centrum Hetmańska
Poznan
Somed CR
Warsaw
Czechia3 sites
CCR Brno, s.r.o
Brno
CCR Czech a.s
Pardubice
CCR Prague, s.r.o
Prague
Denmark3 sites
Sanos Clinic Nordjylland
Gandrup
Sanos Clinic Herlev
Herlev
Sanos Clinic Syddanmark
Vejle
Moldova2 sites
PMSI Cardiology Institute/RTL SM SRL Consultative ward
Chisinau
PMSI Clinical Republican Hospital "Timofei Mosneaga"
Chisinau
About this study
Official title: A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy and Safety of LEVI-04 in Patients With Osteoarthritis of the Knee
This is a phase 2, randomized, double-blind, placebo-controlled trial of multiple doses and multiple administrations of LEVI-04 for the treatment of pain due to osteoarthritis of the knee.
Read the detailed description
The study consists of a Screening Period (including a Diary Run- In/analgesic wash-out Period), Randomization, Post-Randomization Period, and a Follow-up Period. Up to 624 participants will be enrolled and randomized to one of four Treatment Arms at the ratio 1:1:1:1
The overall objective of this study is to evaluate the efficacy and safety of LEVI-04 compared to placebo in patients with knee OA.
- Conditions
- Pain, Osteo Arthritis Knee, Knee Osteoarthritis, Arthritis, Joint Diseases, Musculoskeletal Diseases
- Being tested
- LEVI-04, Placebo
- Keywords
- Osteoarthritis, Knee, Levi-04
- Medical subject headings
- Pain, Osteoarthritis, Knee, Arthritis, Joint Diseases, Musculoskeletal Diseases, Rheumatic Diseases, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LEVI-04Drug
LEVI-04, a fully human chimeric fusion protein that combines the Fc fragment of human immunoglobulin G1 with the p75 neurotrophin receptor (p75 NTR), for the treatment of chronic pain.
PlaceboOther
Saline vehicle
| Study group | Role | What they receive |
|---|---|---|
| 0.3 mg/kg LEVI-04 | Active comparator | Intravenous infusion of 0.3 mg/kg LEVI-04 Receives: Drug: LEVI-04 |
| 1.0 mg/kg LEVI-04 | Active comparator | Intravenous infusion of 1.0 mg/kg LEVI-04 Receives: Drug: LEVI-04 |
| 2.0 mg/kg LEVI-04 | Active comparator | Intravenous infusion of 2.0 mg/kg LEVI-04 Receives: Drug: LEVI-04 |
| Placebo | Placebo comparator | Intravenous infusion of saline vehicle as placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Least Squares Mean Change From Baseline in WOMAC Pain
The primary efficacy endpoint is the change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale score, measured on a 0-10 point scale (0=no pain; 10=worse pain; the result reported is mean change from baseline, therefore the greater the reduction in units the better the outcome)
Measured: Week 17 Change from Baseline
Secondary outcomes (4)
Least Squares Mean Change From Baseline in Post-Staircase Evoked Pain Procedure (StEPP) Pain Intensity
Change from baseline in pain intensity measured following the Staircase Evoked Pain Procedure (StEPP), using a numeric rating scale ranging from 0 to 10 (0=no pain; 10=worse pain; the result reported is mean change from baseline, therefore the greater the reduction in units the better the outcome)
Measured: Week 17 Change from Baseline
Least Squares Mean Change From Baseline in WOMAC Physical Function
Change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Physical Function subscale, measured on a 0 to 10 point scale (0=no impact on physical function; 10=worse impact on physical function; the result reported is mean change from baseline, therefore the greater the reduction in units the better the outcome)
Measured: Week 17 Change from Baseline
Least Squares Mean Change From Baseline in WOMAC Joint Stiffness Subscale
Change from baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Joint Stiffness Subscale, scored on a 0 to 10 point scale (0=no stiffness; 10=worst stiffness; the result reported is mean change from baseline, therefore the greater the reduction in units the better the outcome)
Measured: Week 17 Change from Baseline
Least Squares Mean Change From Baseline in Patient Global Assessment
Change from baseline in the Patient Global Assessment, measured on a 0 to 10 numeric rating scale where 0 indicates "Very good" and 10 indicates "Very bad". The result reported is the mean change from baseline; therefore, the greater the reduction in units, the better the outcome.
Measured: Week 17 Change from Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2022
- Study start19 Oct 2022
- Primary completion20 May 2024
- Study completion20 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized, double-blind, placebo-controlled trial of multiple doses and multiple administrations of LEVI-04 for the treatment of pain due to osteoarthritis of the knee. The study consists of a Screening Period (including a Diary Run- In/analgesic wash-out Period), Randomization, Post-Randomization Period, and a Follow-up Period. Up to 624 participants will be enrolled and randomized to one of four Treatment Arms at the ratio 1:1:1:1.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 518 participants (actual)
Sponsor and investigators
- Lead sponsor
- Levicept
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Nordic Bioscience Clinical Development
- Responsible party
- Sponsor
- Investigators
- Simon Westbrook, Study director, Levicept
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05618782
- Sponsor's protocol ID
- LEVI-04-21-02
- Status last verified
- Nov 2025
- First submitted
- 1 Nov 2022
- Last updated
- 20 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Conaghan PG, Katz N, Bihlet AR, Guermazi A, Rom D, Perkins MC, Hughes B, Herholdt C, Bombelka I, Westbrook S. Efficacy and safety of LEVI-04 in patients with osteoarthritis of the knee: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2026 Mar 28;407(10535):1237-1248. doi: 10.1016/S0140-6736(26)00131-5.
PubMed 41905364