LTG-001 for Osteoarthritis of the knee

Inclusion criteria

• {"criterion_text":"- Must be 40 to 80 years of age inclusive, at the time of signing the informed consent.\n- Has signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.\n- Is willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines and other study procedures, including proper utilization of the study diary, and to communicate meaningfully with study personnel in local language.\n- Is willing to withdraw from any medication for osteoarthritis including, but not limited to, opioids, NSAIDs, COX-2 inhibitors, topical medication, and duloxetine until completion of the EOS visit.\n- Agrees to take only the protocol-permitted medications from the start of the diary run-in phase through the EOS visit.\n- Has a confirmed diagnosis of osteoarthritis of the knee based on the following criteria: a. Has had radiographs of both knees with a posterior-anterior, fixed-flexion view taken during the screening phase; b. Meets ACR clinical and radiographic diagnostic criteria; c. Has evidence of osteoarthritis of the knee with a KL grade of 2 or 3, determined through central reading.\n- Has a history of knee pain on most days for at least 3 months prior to start of the screening phase\n- The pain screening assessment scores assessed in the target knee are both ≥4.0 (on a 0-10 scale) at screening assessments (Visit 1a and Visit 1b).\n- The target knee WOMAC pain subscale scores are ≥4.0 (on a 0-10 scale) at both screening (Visit 1b) and Day 1 predose assessments.\n- Has pain scores during the diary run-in phase that meet the following criteria: a. Has recorded an Average Daily (NPRS) Pain score on at least 6 of the 7 days of the diary run-in phase. b. Has a mean Average Daily (NPRS) Pain score during the diary run-in phase that is ≥5.0 and ≤9.0. c. The standard deviation of Average Daily (NPRS) Pain scores during the diary run-in phase is ≤1.5.\n- Has a BMI ≤38 kg/m2 at screening.\n- If female is of childbearing potential, willing and able to follow contraceptive guidelines\n- If male and sexually active with partner of childbearing potential, willing and able to follow contraceptive guidelines"}

Exclusion criteria

• {"criterion_text":"- Has osteoarthritis of other major joints including but not limited to the nontarget knee, and the severity, in the opinion of the investigator, could interfere with assessment of pain of the target knee.\n- Has had 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.\n- Has had 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\n- Is currently using opioids, including tramadol, of 2 or more instances per week in any week over the 4 weeks prior to screening.\n- Has signs and/or symptoms of significant cardiac disease in the 6 months prior to screening, 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).\n- Has an 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\n- Is pregnant, breast feeding or planning to become pregnant during the time of participation in the study.\n- Has a known allergy to sodium channel blockers or protocol-allowed rescue medication\n- Requires a walker or wheelchair for mobility (walking sticks are permitted).\n- Has a lifetime history of OUD.\n- Has a history of SUD (other than OUD) within the past 2 years.\n- Currently has a comorbid condition, other than osteoarthritis, known to be significantly associated with arthritis or joint pathology, including but not necessarily limited to autoimmune disease with significant joint involvement (eg, Rheumatoid Arthritis or Paget's disease; Seronegative Spondyloarthropathies (eg, Ankylosing Spondylitis, Psoriasis arthritis, Reactive arthritis); or other systemic disease involving the target knee (including endocrinopathies).\n- Has a history of suicidal plan or intent within 2 years of screening and/or current suicidal ideation, as assessed by the investigator.\n- The screening pain assessment scores assessed in the target knee are <2.0 points (out of 10) higher than the scores in the non-target knee at screening (Visit 1a and Visit 1b) and pre-dose on Day 1.\n- Has any comorbid psychiatric disorder causing ongoing, marked psychiatric distress that, in the opinion of the investigator, would interfere with accurate reporting of physical pain symptoms.\n- Has an unmanaged sleep disorder with persistent insomnia that, in the opinion of the investigator, would interfere with accurate reporting of physical pain symptoms\n- Has moderate or or severe hepatic impairment based on clinical judgement, in the opinion of the investigator, or meets diagnostic criteria based on ALT and AST laboratory values outlined in exclusion #34.\n- Has previously used Journavx (suzetrigine) or any other Nav1.8 inhibitor.\n- Is currently using a strong CYP3A4 inhibitor or inducer.\n- Is currently taking medications that have been shown to cause torsade de points. Participants taking medications that are suspected to prolong QT interval must be on a stable regimen, and must not have plans to change those medications during the study.\n- Is currently using any other investigational drugs or devices.\n- Has participated in a previous study investigating LTG-001.\n- Has participated in another investigational study within 30 days (or 90 days for biologics) prior to screening.\n- Is a male or female participant with ECG QTcF >450 msec (applying Fridericia correction), defined as the mean of the QTcF of triplicate ECGs obtained in rapid succession. Participants using allowable medications that are suspected to prolong QT interval (consistent with exclusion #27) will be excluded if their QTcF > 430 ms.\n- Has 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.\n- Has an eGFR of <60 mL/min at screening.\n- Has ALT or AST values >2.0 × upper limit of normal at screening.\n- Has any other abnormal laboratory results indicative of significant medical disease that, in the opinion of the investigator, would preclude the participant’s participation in the study.\n- Has a positive urine drug screen, other than for a known prescribed concomitant medication that is not otherwise exclusionary (eg, benzodiazepines).\n- Is, or has a close relative that is the investigator or a sub-investigator, research assistant, pharmacist, study coordinator or other staff directly involved with the conduct of the study at that site\n- Has a history of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug.\n- Meets any other lifestyle, medication, or other study restrictions\n- Has a hip dislocation and congenital hip dysplasia with degenerative joint disease.\n- Has a 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 the 6 months prior to screening and use of NSAIDs is not required for management of this condition.\n- Has any chronic pain condition besides osteoarthritis for which they have taken medication in the past year, including: neuropathic pain, complex regional pain syndrome, chronic widespread pain syndromes (eg, fibromyalgia), chronic low back pain, migraine.\n- Has a history of significant trauma (eg, intra-articular fracture) or major surgery (excluding injection therapies and arthroscopy) to a knee, hip, or shoulder within the previous 1 year.\n- Has planned a major surgery or other major invasive procedure while participating in the study.\n- Has had surgery or stent placement for coronary artery disease in the 6 months prior to screening."}

Primary endpoints

• {"endpoint_text":"- Change in WOMAC pain subscale score from pre-dose at the start of each treatment period (Day 1, Day 28) to the end of each treatment period (Day 14, Day 41).","definition_or_measurement_approach":"Change in WOMAC pain subscale score measured from pre-dose at Day 1 and Day 28 to end of each treatment period at Day 14 and Day 41."}

Secondary endpoints

• {"endpoint_text":"- Change from baseline (7-day diary run-in) in weekly mean Average and Worst Pain score (via average and worst pain NPRS) each week of each treatment period (Period 1 Week 1 [Days 1-6], Period 1 Week 2 [Days 7-13], Period 2 Week 1 [Days 28-33], Period 2 Week 2 [Days 34-40]).","definition_or_measurement_approach":"Weekly mean Average and Worst Pain scores collected via NPRS compared to 7-day diary run-in baseline; assessed each specified week of each treatment period."}
• {"endpoint_text":"- Change in WOMAC physical function subscale score from pre-dose at the start of each treatment period (Day 1, Day 28) to the end of each treatment period (Day 14, Day 41).","definition_or_measurement_approach":"Change in WOMAC physical function subscale score measured from pre-dose to end of each treatment period (Day 14, Day 41)."}
• {"endpoint_text":"- Change in participant assessment of pain score during StEPP from pre-dose at the start of each treatment period (Day 1, Day 28) to the end of each treatment period (Day 14, Day 41).","definition_or_measurement_approach":"Participant assessment of pain during Staircase Evoked Pain Procedure (StEPP), measured pre-dose and at end of each treatment period."}
• {"endpoint_text":"- Change in WOMAC stiffness subscale score from pre-dose at the start of each treatment period (Day 1, Day 28) to the end of each treatment period (Day 14, Day 41).","definition_or_measurement_approach":"Change in WOMAC stiffness subscale score measured pre-dose to end of each treatment period."}
• {"endpoint_text":"- PGA score at the end of each treatment period (Day 14, Day 41).","definition_or_measurement_approach":"Patient Global Assessment (PGA) score assessed at end of each treatment period."}
• {"endpoint_text":"- Proportion of participants with favorable (rating of “good,” “very good” or “excellent”) PGA of study drug at the end of each treatment period (Day 14, Day 41).","definition_or_measurement_approach":"Proportion of participants rating PGA as 'good', 'very good' or 'excellent' at Day 14 and Day 41."}
• {"endpoint_text":"- Total rescue medication use for target knee during each treatment period.","definition_or_measurement_approach":"Total rescue medication use for the target knee collected during each treatment period (as recorded)."}
• {"endpoint_text":"- Incidence, severity, and relatedness of TEAEs, SAEs, discontinuations due to TEAEs, and deaths.","definition_or_measurement_approach":"Safety assessments including treatment-emergent adverse events, serious adverse events, discontinuations due to TEAEs, and deaths as recorded during study."}
• {"endpoint_text":"- Change from baseline in vital signs, ECG, and laboratory test values.","definition_or_measurement_approach":"Changes in vital signs, ECG, and laboratory values from baseline measured at scheduled visits."}
• {"endpoint_text":"- Plasma concentrations of LTG-001 and its metabolites after the first and last dose of study drug in the active treatment period.","definition_or_measurement_approach":"Pharmacokinetic measurement of plasma concentrations of LTG-001 and metabolites after first and last dose in active treatment period."}

Methods

• Online recruitment platform (Studies and Me Recruitment) — online channel; target audience: patients with osteoarthritis of the knee; country: Denmark (sponsor third-party duty: Online recruitment platform).
• Site-based recruitment via Sanos A/S clinic units (clinic department/clinic unit/Phase 1 unit) — recruitment at clinic locations in Denmark.

Denmark

Earliest CTIS Part Ii Submission Date

06-10-2025

Latest Decision Or Authorization Date

10-11-2025

Processing Time Days

35

Number Of Sites

3

Number Of Participants

180

Primary sponsor

Full Name

Latigo Biotherapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Development LP

Responsibilities

PK Laboratory Analysis

Name

Everest Clinical Research Corporation

Third parties

• {"country":"Belgium","full_name":"Montrium Europe SRL","duties_or_roles":"eTMF","organisation_type":"Industry"}
• {"country":"Denmark","full_name":"Nordic Bioscience A/S","duties_or_roles":"Central lab","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Sanos Supply A/S","duties_or_roles":"IMP and RM sourcing and distribution","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Everest Clinical Research Corporation","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"NBCD A/S","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"PK Laboratory Analysis","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Ozack ApS","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Studies and Me Recruitment","duties_or_roles":"Online recruitment platform","organisation_type":"Industry"}
• {"country":"Denmark","full_name":"Sply ApS","duties_or_roles":"IMP and RM logistics","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Assistek Inc.","duties_or_roles":"e-Diary","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Clario","duties_or_roles":"Staircase Evoked Pain Procedure (StEPP)","organisation_type":"Industry"}