Clinical Trial to Evaluate the Efficacy and Safety of LEVI-04 in Patients With Osteoarthritis of the Knee

NCT05618782 | Completed Phase 2 Results

• 1 other identifier: LEVI-04-21-02
• Study Type: interventional
• Target: 518
• Locations: 5 countries
• Sites: 13

Brief 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.

Conditions

Pain; Osteo Arthritis Knee; Knee Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Keywords

Osteoarthritis; Knee; Levi-04

Outcome Measures

Primary Outcomes (1)

• 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)

  Week 17 Change from Baseline

Secondary Outcomes (4)

• Least Squares Mean Change From Baseline in Post-Staircase Evoked Pain Procedure (StEPP) Pain Intensity

  Week 17 Change from Baseline

• Least Squares Mean Change From Baseline in WOMAC Physical Function

  Week 17 Change from Baseline

• Least Squares Mean Change From Baseline in WOMAC Joint Stiffness Subscale

  Week 17 Change from Baseline

• Least Squares Mean Change From Baseline in Patient Global Assessment

  Week 17 Change from Baseline

Study Arms (4)

0.3 mg/kg LEVI-04

ACTIVE COMPARATOR

Intravenous infusion of 0.3 mg/kg LEVI-04

Drug: LEVI-04

1.0 mg/kg LEVI-04

ACTIVE COMPARATOR

Intravenous infusion of 1.0 mg/kg LEVI-04

Drug: LEVI-04

2.0 mg/kg LEVI-04

ACTIVE COMPARATOR

Intravenous infusion of 2.0 mg/kg LEVI-04

Drug: LEVI-04

Placebo

PLACEBO COMPARATOR

Intravenous infusion of saline vehicle as placebo

Other: Placebo

Interventions

LEVI-04 DRUG

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.

0.3 mg/kg LEVI-04; 1.0 mg/kg LEVI-04; 2.0 mg/kg LEVI-04

Placebo OTHER

Saline vehicle

Placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Levicept: lead
• Nordic Bioscience Clinical Development (NBCD): collaborator

Study Sites (13)

CCR Brno, s.r.o

Brno, Czechia

Location

CCR Czech a.s

Pardubice, Czechia

Location

CCR Prague, s.r.o

Prague, Czechia

Location

Sanos Clinic Nordjylland

Gandrup, Denmark

Location

Sanos Clinic Herlev

Herlev, Denmark

Location

Sanos Clinic Syddanmark

Vejle, Denmark

Location

Hong Kong Center for Clinical Research

Hong Kong, Hong Kong

Location

PMSI Cardiology Institute/RTL SM SRL Consultative ward

Chisinau, Moldova

Location

PMSI Clinical Republican Hospital "Timofei Mosneaga"

Chisinau, Moldova

Location

NZOZ Bif-Med. s.c.

Bytom, Poland

Location

Somed CR

Lodz, Poland

Location

Medyczne Centrum Hetmańska

Poznan, Poland

Location

Somed CR

Warsaw, Poland

Location

MeSH Terms

Conditions

Pain; Osteoarthritis, Knee; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Osteoarthritis

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Iwona Bombelka
• Organization: Levicept

info@levicept.com

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Study Officials

• Simon Westbrook

  Levicept

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double- Blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: November 1, 2022
• First Posted: November 16, 2022
• Study Start: October 19, 2022
• Primary Completion: May 20, 2024
• Study Completion: May 20, 2024
• Last Updated: November 20, 2025
• Results First Posted: October 6, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CZ (3); PL (4); DK (3); MO (2); HK (1)