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Completed

NCT Number: NCT03133676

A Study Evaluating the Safety, Pharmacokinetics, and Pharmacodynamics of KA34 in Subjects With Knee Osteoarthritis

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

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Key information

Conditions

Osteoarthritis, Knee Arthritis Joint Diseases Musculoskeletal Diseases Osteoarthritis Rheumatic Diseases

Age range

40 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Diablo Clinical Research, Walnut Creek, California, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

KA34

Drug

50 µg - 400 µg intra-articular injection (single or multiple doses)

Other names: KA-34

Placebo

Drug

50 µg - 400 µg intra-articular injection (single or multiple doses)

Primary outcomes

  1. SAD Part: Number of Subjects Who Experienced Treatment Emergent Adverse Events (TEAEs)

    Time frame: Day 1 up to Day 29

    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.

  2. MAD Part: Number of Subjects Who Experienced TEAEs

    Time frame: Day 1 up to Day 180

    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.

Secondary outcomes

  1. SAD Part: Mean Change From Baseline in Hemoglobin at Day 8

    Time frame: Baseline and Day 8

    The mean changes from baseline at Day 8 in hemoglobin levels for subjects in the SAD part of the study are presented.

  2. MAD Part: Mean Change From Baseline in Hemoglobin at Day 180

    Time frame: Baseline and Day 180

    The mean changes from baseline at Day 180 in hemoglobin levels for subjects in the MAD part of the study are presented.

  3. SAD Part: Mean Change From Baseline in Hematocrit at Day 8

    Time frame: Baseline and Day 8

    The mean changes from baseline at Day 8 in hematocrit levels for subjects in the SAD part of the study are presented.

  4. MAD Part: Mean Change From Baseline in Hematocrit at Day 180

    Time frame: Baseline and Day 180

    The mean changes from baseline at Day 180 in hematocrit levels for subjects in the MAD part of the study are presented.

  5. SAD Part: Mean Change From Baseline in Total Bilirubin and Creatinine at Day 8

    Time frame: Baseline and Day 8

    The mean changes from baseline at Day 8 in total bilirubin and creatinine for subjects in the SAD part of the study are presented.

  6. MAD Part: Mean Change From Baseline in Total Bilirubin and Creatinine at Day 180

    Time frame: Baseline and Day 180

    The mean changes from baseline at Day 180 in total bilirubin and creatinine for subjects in the MAD part of the study are presented.

  7. SAD Part: Mean Change From Baseline in Liver Enzymes at Day 8

    Time frame: Baseline and Day 8

    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).

  8. MAD Part: Mean Change From Baseline in Liver Enzymes at Day 180

    Time frame: Baseline and Day 180

    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.

  9. SAD Part: Mean Change From Baseline in Systolic and Diastolic Blood Pressure at Day 8

    Time frame: Baseline and Day 8

    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.

  10. MAD Part: Mean Change From Baseline in SBP and DBP at Day 180

    Time frame: Baseline and Day 180

    The mean changes from baseline at Day 180 in SBP and DBP for subjects in the MAD part of the study are presented.

  11. SAD Part: Mean Change From Baseline in the QTcF Interval at Day 8

    Time frame: Baseline and Day 8

    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.

  12. MAD Part: Mean Change From Baseline in the QTcF Interval at Day 180

    Time frame: Baseline and Day 180

    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.

  13. SAD Part: Number of Subjects With Injection Site TEAEs

    Time frame: Baseline up to Day 29

    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.

  14. MAD Part: Number of Subjects With Injection Site TEAEs

    Time frame: Baseline up to Day 180

    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.

  15. SAD Part: Mean Maximum Plasma Concentration (Cmax)

    Time frame: Pre-dose up to 4 hours post-dose on Day 1

    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.

  16. 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

    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.

  17. SAD Part: Median Time to Maximum Observed Plasma Concentration (Tmax)

    Time frame: Pre-dose up to 4 hours post-dose on Day 1

    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.

  18. 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

    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.

  19. 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

    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.

  20. 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

    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.

  21. 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

    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.

  22. 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

    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.

  23. SAD Part: Mean Apparent Terminal Half-life (t1/2)

    Time frame: Pre-dose up to 4 hours post-dose on Day 1

    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.

  24. 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

    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.

  25. SAD Part: Mean Apparent Clearance (CL/F)

    Time frame: Pre-dose up to 4 hours post-dose on Day 1

    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.

  26. 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

    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.

  27. SAD Part: Mean Apparent Volume of Distribution (Vz/F)

    Time frame: Pre-dose up to 4 hours post-dose on Day 1

    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.

  28. 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

    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.

Sponsors and collaborators

Lead sponsor

Calibr, a division of Scripps Research

Other

Collaborators

  • California Institute for Regenerative Medicine (CIRM)

Registry information

Official study 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

Important dates

Study start
2018
Primary completion
2020
Study completion
2020
First posted
Apr 28, 2017
Registry last updated
Dec 27, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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