- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03133676
A Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of KA34 in Subjects With Knee Osteoarthritis
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 Overview
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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California
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Walnut Creek, California, United States, 94598
- Diablo Clinical Research
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Florida
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Clearwater, Florida, United States, 33765
- Clinical Research of West Florida
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Orlando, Florida, United States, 32806
- Bioclinica Research
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Pennsylvania
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Duncansville, Pennsylvania, United States, 16635
- Altoona Center for Clinical Research
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: KA34 Active Drug
KA34 active drug in the dose range of 50 - 400 ug per knee
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50 µg - 400 µg intra-articular injection (single or multiple doses)
Other Names:
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Placebo Comparator: Placebo
Placebo is the formulation for KA34.
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50 µg - 400 µg intra-articular injection (single or multiple doses)
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
SAD Part: Number of Subjects Who Experienced Treatment Emergent Adverse Events (TEAEs)
Time Frame: Day 1 up to Day 29
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TEAEs were collected from time of first administration of IP (Day 1) until 28 days after the last administration of IP. The severity of TEAEs was classified by the investigator as mild, moderate or severe and graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The investigator also assessed relatedness of TEAEs. The number of subjects who experienced any TEAEs, serious TEAEs (SAE), related TEAEs and TEAEs with CTCAE Grade ≥ 3 are presented. |
Day 1 up to Day 29
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MAD Part: Number of Subjects Who Experienced TEAEs
Time Frame: Day 1 up to Day 180
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TEAEs were collected from time of first administration of IP (Day 1) until 30 days after the last administration of IP. The severity of TEAEs was classified by the investigator as mild, moderate or severe and graded using the CTCAE version 5.0. The investigator also assessed relatedness of TEAEs. The number of subjects who experienced any TEAEs, SAEs, related TEAEs and TEAEs with CTCAE Grade ≥ 3 are presented. |
Day 1 up to Day 180
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
SAD Part: Mean Change From Baseline in Hemoglobin at Day 8
Time Frame: Baseline and Day 8
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The mean changes from baseline at Day 8 in hemoglobin levels for subjects in the SAD part of the study are presented.
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Baseline and Day 8
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MAD Part: Mean Change From Baseline in Hemoglobin at Day 180
Time Frame: Baseline and Day 180
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The mean changes from baseline at Day 180 in hemoglobin levels for subjects in the MAD part of the study are presented.
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Baseline and Day 180
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SAD Part: Mean Change From Baseline in Hematocrit at Day 8
Time Frame: Baseline and Day 8
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The mean changes from baseline at Day 8 in hematocrit levels for subjects in the SAD part of the study are presented.
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Baseline and Day 8
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MAD Part: Mean Change From Baseline in Hematocrit at Day 180
Time Frame: Baseline and Day 180
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The mean changes from baseline at Day 180 in hematocrit levels for subjects in the MAD part of the study are presented.
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Baseline and Day 180
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SAD Part: Mean Change From Baseline in Total Bilirubin and Creatinine at Day 8
Time Frame: Baseline and Day 8
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The mean changes from baseline at Day 8 in total bilirubin and creatinine for subjects in the SAD part of the study are presented.
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Baseline and Day 8
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MAD Part: Mean Change From Baseline in Total Bilirubin and Creatinine at Day 180
Time Frame: Baseline and Day 180
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The mean changes from baseline at Day 180 in total bilirubin and creatinine for subjects in the MAD part of the study are presented.
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Baseline and Day 180
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SAD Part: Mean Change From Baseline in Liver Enzymes at Day 8
Time Frame: Baseline and Day 8
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The mean changes from baseline at Day 8 in the following liver enzyme levels are presented for subjects in the SAD part of the study: alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
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Baseline and Day 8
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MAD Part: Mean Change From Baseline in Liver Enzymes at Day 180
Time Frame: Baseline and Day 180
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The mean changes from baseline at Day 180 in the following liver enzyme levels are presented for subjects in the MAD part of the study: ALP, ALT and AST.
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Baseline and Day 180
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SAD Part: Mean Change From Baseline in Systolic and Diastolic Blood Pressure at Day 8
Time Frame: Baseline and Day 8
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The mean changes from baseline at Day 8 in systolic blood pressure (SBP) and diastolic blood pressure (DBP) for subjects in the SAD part of the study are presented.
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Baseline and Day 8
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MAD Part: Mean Change From Baseline in SBP and DBP at Day 180
Time Frame: Baseline and Day 180
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The mean changes from baseline at Day 180 in SBP and DBP for subjects in the MAD part of the study are presented.
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Baseline and Day 180
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SAD Part: Mean Change From Baseline in the QTcF Interval at Day 8
Time Frame: Baseline and Day 8
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The mean changes from baseline at Day 8 in the electrocardiogram (ECG) parameter QTcF interval for subjects in the SAD part of the study are presented.
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Baseline and Day 8
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MAD Part: Mean Change From Baseline in the QTcF Interval at Day 180
Time Frame: Baseline and Day 180
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The mean changes from baseline at Day 180 in the ECG parameter QTcF interval for subjects in the MAD part of the study are presented.
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Baseline and Day 180
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SAD Part: Number of Subjects With Injection Site TEAEs
Time Frame: Baseline up to Day 29
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Physical examinations were conducted by a physician or another medically-qualified individual and findings were noted at the injection site during the study.
The number of subjects with injection site TEAEs, including the following, are presented: Injection site erythema, Injection site hypersensitivity, Injection site inflammation, Injection site joint discomfort, Injection site joint inflammation, Injection site joint pain, Injection site joint swelling, Injection site nodule, Injection site pain and Injection site swelling.
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Baseline up to Day 29
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MAD Part: Number of Subjects With Injection Site TEAEs
Time Frame: Baseline up to Day 180
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Physical examinations were conducted by a physician or another medically-qualified individual and findings were noted at the injection site during the study.
The number of subjects with injection site TEAEs, including the following, are presented: Injection site erythema, Injection site hypersensitivity, Injection site inflammation, Injection site joint discomfort, Injection site joint inflammation, Injection site joint pain, Injection site joint swelling, Injection site nodule, Injection site pain and Injection site swelling.
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Baseline up to Day 180
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SAD Part: Mean Maximum Plasma Concentration (Cmax)
Time Frame: Pre-dose up to 4 hours post-dose on Day 1
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All Pharmacokinetic (PK) samples were analyzed by liquid chromatography with tandem mass spectrometry, using a validated, sensitive, specific method.
Cmax values were obtained directly from the observed concentration versus time data, and the geometric mean Cmax values for subjects who received KA34 in the SAD part of the study are presented.
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Pre-dose up to 4 hours post-dose on Day 1
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MAD Part: Mean Cmax
Time Frame: Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
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All PK samples were analyzed by liquid chromatography with tandem mass spectrometry, using a validated, sensitive, specific method.
Cmax values were obtained directly from the observed concentration versus time data, and the geometric mean Cmax values for subjects who received KA34 in the MAD part of the study are presented.
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Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
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SAD Part: Median Time to Maximum Observed Plasma Concentration (Tmax)
Time Frame: Pre-dose up to 4 hours post-dose on Day 1
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All PK samples were analyzed by liquid chromatography with tandem mass spectrometry, using a validated, sensitive, specific method.
Tmax was obtained directly from the observed concentration versus time data and the median Tmax values for subjects who received KA34 in the SAD part of the study are presented.
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Pre-dose up to 4 hours post-dose on Day 1
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MAD Part: Median Tmax
Time Frame: Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
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All PK samples were analyzed by liquid chromatography with tandem mass spectrometry, using a validated, sensitive, specific method.
Tmax was obtained directly from the observed concentration versus time data and the median Tmax values for subjects who received KA34 in the MAD part of the study are presented.
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Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
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SAD Part: Mean Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC[0-t])
Time Frame: Pre-dose up to 4 hours post-dose on Day 1
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All PK samples were analyzed by liquid chromatography with tandem mass spectrometry, using a validated, sensitive, specific method.
AUC(0-t) was calculated by linear up/log down trapezoidal summation, and the mean AUC(0-t) values for subjects who received KA34 in the SAD part of the study are presented.
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Pre-dose up to 4 hours post-dose on Day 1
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MAD Part: Mean AUC(0-t)
Time Frame: Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
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All PK samples were analyzed by liquid chromatography with tandem mass spectrometry, using a validated, sensitive, specific method.
AUC(0-t) was calculated by linear up/log down trapezoidal summation, and the mean AUC(0-t) values for subjects who received KA34 in the MAD part of the study are presented.
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Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
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SAD Part: Mean Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUC[0-inf])
Time Frame: Pre-dose up to 4 hours post-dose on Day 1
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All PK samples were analyzed by liquid chromatography with tandem mass spectrometry, using a validated, sensitive, specific method.
AUC(0-inf) was calculated by linear up/log down trapezoidal summation and extrapolated to infinity by the addition of the last quantifiable concentration (Clast) divided by the elimation rate constant (λz), i.e.
AUC(0-t) + Clast/λz.
The mean AUC(0-inf) values for subjects who received KA34 in the SAD part of the study are presented.
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Pre-dose up to 4 hours post-dose on Day 1
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MAD Part: Mean AUC(0-inf)
Time Frame: Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
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All PK samples were analyzed by liquid chromatography with tandem mass spectrometry, using a validated, sensitive, specific method.
AUC(0-inf) was calculated by linear up/log down trapezoidal summation and extrapolated to infinity by the addition of the last quantifiable concentration (Clast) divided by the elimation rate constant (λz), i.e.
AUC(0-t) + Clast/λz.
The mean AUC(0-inf) values are presented for subjects who received KA34 in the MAD part of the study.
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Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
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SAD Part: Mean Apparent Terminal Half-life (t1/2)
Time Frame: Pre-dose up to 4 hours post-dose on Day 1
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All PK samples were analyzed by liquid chromatography with tandem mass spectrometry, using a validated, sensitive, specific method.
t1/2 was determined as the natural log of λz, i.e. as ln2/λz.
Mean t1/2 values for subjects who received KA34 in the SAD part of the study are presented.
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Pre-dose up to 4 hours post-dose on Day 1
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MAD Part: Mean t1/2
Time Frame: Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
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All PK samples were analyzed by liquid chromatography with tandem mass spectrometry, using a validated, sensitive, specific method.
t1/2 was determined as the natural log of λz, i.e. as ln2/λz.
Mean t1/2 values for subjects who received KA34 in the MAD part of the study are presented.
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Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
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SAD Part: Mean Apparent Clearance (CL/F)
Time Frame: Pre-dose up to 4 hours post-dose on Day 1
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All PK samples were analyzed by liquid chromatography with tandem mass spectrometry, using a validated, sensitive, specific method.
The CL/F after extravascular dosing was calculated as dose divided by AUC(0-inf), and is presented for subjects who received KA34 in the SAD part of the study.
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Pre-dose up to 4 hours post-dose on Day 1
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MAD Part: Mean CL/F
Time Frame: Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
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All PK samples were analyzed by liquid chromatography with tandem mass spectrometry, using a validated, sensitive, specific method.
The CL/F after extravascular dosing was calculated as dose divided by AUC(0-inf), and is presented for subjects who received KA34 in the MAD part of the study.
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Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
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SAD Part: Mean Apparent Volume of Distribution (Vz/F)
Time Frame: Pre-dose up to 4 hours post-dose on Day 1
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The Vz/F was calculated as dose divided by (λz*AUC[0-inf]), and the mean Vz/F values for subjects who received KA34 in the SAD part of the study are presented.
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Pre-dose up to 4 hours post-dose on Day 1
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MAD Part: Mean Vz/F
Time Frame: Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
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The Vz/F was calculated as dose divided by (λz*AUC[0-inf]), and the mean Vz/F values for subjects who received KA34 in the MAD part of the study are presented.
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Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29
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Collaborators and Investigators
Collaborators
Investigators
- Study Director: Martin Lotz, MD, Calibr, a division of Scripps Research
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CBR-KA34-3001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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