An efficacy and safety study of LTG-001 in osteoarthritis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Latigo Biotherapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Decision date (initial)

2025-11-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic

To evaluate the efficacy of LTG-001 compared to placebo in treating pain associated with osteoarthritis of the knee

Secondary objectives 3

1. To further evaluate the efficacy of LTG-001 compared to placebo in treating pain associated with osteoarthritis of the knee
2. To evaluate the safety and tolerability of LTG-001
3. To estimate the population PK of LTG-001

Conditions and MedDRA coding

Osteoarthritis of the knee

Regulatory references

Plan to share IPD

Yes

IPD plan description

Data obtained through this study may be provided to qualified researchers on request in accordance with international principles for responsible research (under the European Federation of Pharmaceutical Industries and Associations (EFPIA). Approval of the request (including e.g. research proposal and statistical analysis plan) and execution of all applicable agreements (i.e. a data sharing agreement) are prerequisites to the sharing of data with the requesting party. Data will only be shared in encoded form to protect participant identity and with requirements for data protection as well as requirements against unauthorized use and disclosure. Participant identity will remain confidential. Participants can inquire about data transfers and security measures at any time by contacting the trial physician.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Must be 40 to 80 years of age inclusive, at the time of signing the informed consent.
2. 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.
3. Has a history of knee pain on most days for at least 3 months prior to start of the screening phase
4. 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).
5. 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.
6. 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.
7. Has a BMI ≤38 kg/m2 at screening.
8. If female is of childbearing potential, willing and able to follow contraceptive guidelines
9. If male and sexually active with partner of childbearing potential, willing and able to follow contraceptive guidelines
10. Has signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
11. 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.
12. 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.
13. Agrees to take only the protocol-permitted medications from the start of the diary run-in phase through the EOS visit.

Exclusion criteria 39

1. 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.
2. 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).
3. Has osteoarthritis or other potentially serious joint pathology in any joint that is deemed rapidly progressive
4. Has a hip dislocation and congenital hip dysplasia with degenerative joint disease.
5. 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.
6. 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.
7. 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.
8. Has planned a major surgery or other major invasive procedure while participating in the study.
9. Has had surgery or stent placement for coronary artery disease in the 6 months prior to screening.
10. 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.
11. 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
12. Is currently using opioids, including tramadol, of 2 or more instances per week in any week over the 4 weeks prior to screening.
13. 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).
14. 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
15. Is pregnant, breast feeding or planning to become pregnant during the time of participation in the study.
16. Has a known allergy to sodium channel blockers or protocol-allowed rescue medication
17. Requires a walker or wheelchair for mobility (walking sticks are permitted).
18. Has a lifetime history of OUD.
19. Has a history of SUD (other than OUD) within the past 2 years.
20. Has a history of suicidal plan or intent within 2 years of screening and/or current suicidal ideation, as assessed by the investigator.
21. 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.
22. 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.
23. Has an unmanaged sleep disorder with persistent insomnia that, in the opinion of the investigator, would interfere with accurate reporting of physical pain symptoms
24. 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.
25. Has previously used Journavx (suzetrigine) or any other Nav1.8 inhibitor.
26. Is currently using a strong CYP3A4 inhibitor or inducer.
27. 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.
28. Is currently using any other investigational drugs or devices.
29. Has participated in a previous study investigating LTG-001.
30. Has participated in another investigational study within 30 days (or 90 days for biologics) prior to screening.
31. 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.
32. 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.
33. Has an eGFR of <60 mL/min at screening.
34. Has ALT or AST values >2.0 × upper limit of normal at screening.
35. 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.
36. Has a positive urine drug screen, other than for a known prescribed concomitant medication that is not otherwise exclusionary (eg, benzodiazepines).
37. 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
38. 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.
39. Meets any other lifestyle, medication, or other study restrictions

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 10

1. 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]).
2. 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).
3. 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).
4. 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).
5. PGA score at the end of each treatment period (Day 14, Day 41).
6. 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).
7. Total rescue medication use for target knee during each treatment period.
8. Incidence, severity, and relatedness of TEAEs, SAEs, discontinuations due to TEAEs, and deaths.
9. Change from baseline in vital signs, ECG, and laboratory test values.
10. Plasma concentrations of LTG-001 and its metabolites after the first and last dose of study drug in the active treatment period.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Latigo Biotherapeutics Inc.

Sponsor organisation

Latigo Biotherapeutics Inc.

Address

1290 Rancho Conejo Boulevard Suite 102

City

Thousand Oaks

Postcode

91320-1408

Country

United States

Scientific contact point

Organisation

Latigo Biotherapeutics Inc.

Contact name

Vice President, Regulatory

Public contact point

Organisation

Latigo Biotherapeutics Inc.

Contact name

Vice President, Regulatory

Third parties 11

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications