Clinical trial NCT03133676: A Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of KA34 in Subjects With Knee Osteoarthritis
Official title: A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of KA34 Administered Via Intra-Articular Injection in Subjects With Osteoarthritis of the Knee
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Osteoarthritis, Knee
Keywords: Osteoarthritis
Arthritis
Joint Disease
Osteoarthritis, Knee
Lead sponsor: Calibr, a division of Scripps Research
Sponsor class: OTHER
Collaborators: name: California Institute for Regenerative Medicine (CIRM)
First posted: 2017-04-28
Enrollment: 60
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the safety and tolerability of KA34 when administered via intra-articular injection to subjects with osteoarthritis of the knee.

Detailed description: This is a randomized, double-blind, placebo-controlled study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of KA34 when administered via intra-articular injection to subjects with osteoarthritis of the knee. OA patients are randomized to receive either placebo or KA34 active drug in the range of 50-400 ug by intra-articular injection. The first portion of the study is with single ascending doses, the second portion of the study is with multiple ascending doses.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of localized osteoarthritis of the knee
* Males willing to use contraception and females who are no longer able to bear children

Exclusion Criteria:

* Body Mass Index (BMI) \> 40
* Grade 0, 3 or 4 osteoarthritis on the Kellgren and Lawrence classification system
* Injury to the knee or other joint within the last 12 months
* Receipt of any investigational product or experimental therapeutic procedure within the last 12 weeks

Primary outcomes:
measure: SAD Part: Number of Subjects Who Experienced Treatment Emergent Adverse Events (TEAEs)
timeFrame: Day 1 up to Day 29
measure: MAD Part: Number of Subjects Who Experienced TEAEs
timeFrame: Day 1 up to Day 180
Secondary outcomes:
measure: SAD Part: Mean Change From Baseline in Hemoglobin at Day 8
timeFrame: Baseline and Day 8
measure: MAD Part: Mean Change From Baseline in Hemoglobin at Day 180
timeFrame: Baseline and Day 180
measure: SAD Part: Mean Change From Baseline in Hematocrit at Day 8
timeFrame: Baseline and Day 8
measure: MAD Part: Mean Change From Baseline in Hematocrit at Day 180
timeFrame: Baseline and Day 180
measure: SAD Part: Mean Change From Baseline in Total Bilirubin and Creatinine at Day 8
timeFrame: Baseline and Day 8
measure: MAD Part: Mean Change From Baseline in Total Bilirubin and Creatinine at Day 180
timeFrame: Baseline and Day 180
measure: SAD Part: Mean Change From Baseline in Liver Enzymes at Day 8
timeFrame: Baseline and Day 8
measure: MAD Part: Mean Change From Baseline in Liver Enzymes at Day 180
timeFrame: Baseline and Day 180
measure: SAD Part: Mean Change From Baseline in Systolic and Diastolic Blood Pressure at Day 8
timeFrame: Baseline and Day 8
measure: MAD Part: Mean Change From Baseline in SBP and DBP at Day 180
timeFrame: Baseline and Day 180
measure: SAD Part: Mean Change From Baseline in the QTcF Interval at Day 8
timeFrame: Baseline and Day 8
measure: MAD Part: Mean Change From Baseline in the QTcF Interval at Day 180
timeFrame: Baseline and Day 180
measure: SAD Part: Number of Subjects With Injection Site TEAEs
timeFrame: Baseline up to Day 29
measure: MAD Part: Number of Subjects With Injection Site TEAEs
timeFrame: Baseline up to Day 180
measure: SAD Part: Mean Maximum Plasma Concentration (Cmax)
timeFrame: Pre-dose up to 4 hours post-dose on Day 1
measure: MAD Part: Mean Cmax
timeFrame: Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
measure: SAD Part: Median Time to Maximum Observed Plasma Concentration (Tmax)
timeFrame: Pre-dose up to 4 hours post-dose on Day 1
measure: MAD Part: Median Tmax
timeFrame: Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
measure: SAD Part: Mean Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC[0-t])
timeFrame: Pre-dose up to 4 hours post-dose on Day 1
measure: MAD Part: Mean AUC(0-t)
timeFrame: Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
measure: SAD Part: Mean Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUC[0-inf])
timeFrame: Pre-dose up to 4 hours post-dose on Day 1
measure: MAD Part: Mean AUC(0-inf)
timeFrame: Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
measure: SAD Part: Mean Apparent Terminal Half-life (t1/2)
timeFrame: Pre-dose up to 4 hours post-dose on Day 1
measure: MAD Part: Mean t1/2
timeFrame: Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
measure: SAD Part: Mean Apparent Clearance (CL/F)
timeFrame: Pre-dose up to 4 hours post-dose on Day 1
measure: MAD Part: Mean CL/F
timeFrame: Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
measure: SAD Part: Mean Apparent Volume of Distribution (Vz/F)
timeFrame: Pre-dose up to 4 hours post-dose on Day 1
measure: MAD Part: Mean Vz/F
timeFrame: Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
Other outcomes:
Locations:
city: Walnut Creek
country: United States
facility: Diablo Clinical Research
state: California
city: Clearwater
country: United States
facility: Clinical Research of West Florida
state: Florida
city: Orlando
country: United States
facility: Bioclinica Research
state: Florida
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
Study officials:
affiliation: Calibr, a division of Scripps Research
name: Martin Lotz, MD
role: STUDY_DIRECTOR
References: