First-in-human, Safety, Tolerability and Pharmacokinetics Study of LRX712 in Osteoarthritic Patients

Study Overview
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Brief Summary
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This study is designed to evaluate, for the first time in humans, safety and tolerability of single ascending doses of intra-articular (i.a.) injections of LRX712 into the knee of patients with moderate osteoarthritis (OA), in order to support the further clinical development. This study will also allow establishment of the systemic and local pharmacokinetics (PK) of LRX712 and the exploration of biomarkers of cartilage breakdown and regeneration in OA patients.

Official Title
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A Randomized, Placebo Controlled, Subject and Investigator Blinded, first-in- Human, Single Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics After Intra-articular Injection of LRX712 Into the Knee of Osteoarthritic Patients

Conditions
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Patients With Moderate Knee Osteoarthritis (30 - 65 Years)

Intervention / Treatment
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* Drug: LRX712
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients, 30 to 65 years of age inclusive, and in good health as determined by medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening. At screening, and at baseline vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position after the subject has rested for at least three minutes, and again (when required) after three minutes in the standing position as outlined in the SOM. Sitting vital signs should be guided by the following ranges: body temperature between 35.0-37.5 °C systolic blood pressure 90-139 mm Hg diastolic blood pressure 50-89 mm Hg pulse rate, 40 - 90 bpm • Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 32 kg/m2. BMI = Body weight (kg) / [Height (m)] Exclusion Criteria: Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant. Pregnant or nursing (lactating) women Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations A history of clinically significant ECG abnormalities, or any of the following ECG abnormalities at screening and baseline PR > 200 msec QRS complex > 120 msec QTcF > 450 msec (males) QTcF > 460 msec (females) Known family history or known presence of long QT syndrome

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LRX712<br>LRX712 given intra-articularly | Drug: LRX712<br>* Ascending single dose on Day 1<br>|
| Placebo Comparator: Placebo<br>Placebo given intra-articularly | Drug: Placebo<br>* Ascending single dose on Day 1<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of LRX712 after a single intra-articular (i.a.) injection in Osteoarthritic (OA) patients | To evaluate Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) of LRX712 after a single i.a. injection in osteoarthritic patients | Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Reach the Maximum Plasma Concentration (Tmax) | To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Time to Reach the Maximum Plasma Concentration (Tmax) | pre-dose to 29 days post-dose | 
| Maximum Observed Plasma Concentration (Cmax) | To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Maximum Observed Plasma Concentration (Cmax) | pre-dose to 29 days post-dose | 
| Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) | To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Area Under the Plasma Concentration-time Curve From 0 to the Last Measurable Concentration (AUClast) | pre-dose to 29 days post-dose | 
| Area under the plasma concentration-time curve from time zero to infinity (AUCinf) | To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Area under the plasma concentration-time curve from time zero to infinity (AUCinf) | pre-dose to 29 days post-dose | 
| Half-life (T1/2) | To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Half-life (T1/2) | pre-dose to 29 days post-dose | 
| CL/F - Total clearance | To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - CL/F - Total clearance | pre-dose to 29 days post-dose | 
| Vz/F - Volume of Distribution | To evaluate LRX712 and metabolite MAE344 pharmacokinetics in plasma - Vz/F - Volume of Distribution | pre-dose to 29 days post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Osteoarthritic patients, Cartilage, Safety