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

Novartis

Status and phase: Completed; Phase 1

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

Treatments: Drug: Placebo; Drug: LRX712

Study type: Interventional

Funder types: Industry

Identifiers

NCT03355196

CLRX712X2101

Details and patient eligibility

About

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.

Enrollment: 42 patients

Sex: All

Ages: 30 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Parallel Assignment

Masking: Double Blind

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42 participants in 2 patient groups, including a placebo group

LRX712

Experimental group

Description:

LRX712 given intra-articularly

Treatment:

Drug: LRX712

Placebo

Placebo Comparator group

Description:

Placebo given intra-articularly

Treatment:

Drug: Placebo