Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03133676
Recruitment Status : Completed
First Posted : April 28, 2017
Results First Posted : May 17, 2021
Last Update Posted : October 27, 2021
Sponsor:
Collaborator:
California Institute for Regenerative Medicine (CIRM)
Information provided by (Responsible Party):
Calibr, a division of Scripps Research

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.

Condition or disease Intervention/treatment Phase
Osteoarthritis, Knee Drug: KA34 Drug: Placebo Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : May 2, 2018
Actual Primary Completion Date : April 28, 2020
Actual Study Completion Date : April 28, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoarthritis

Arm Intervention/treatment
Experimental: KA34 Active Drug
KA34 active drug in the dose range of 50 - 400 ug per knee
Drug: KA34
50 µg - 400 µg intra-articular injection (single or multiple doses)
Other Name: KA-34

Placebo Comparator: Placebo
Placebo is the formulation for KA34.
Drug: Placebo
50 µg - 400 µg intra-articular injection (single or multiple doses)




Primary Outcome Measures :
  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 Outcome Measures :
  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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   40 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03133676


Locations
Layout table for location information
United States, California
Diablo Clinical Research
Walnut Creek, California, United States, 94598
United States, Florida
Clinical Research of West Florida
Clearwater, Florida, United States, 33765
Bioclinica Research
Orlando, Florida, United States, 32806
United States, Pennsylvania
Altoona Center for Clinical Research
Duncansville, Pennsylvania, United States, 16635
Sponsors and Collaborators
Calibr, a division of Scripps Research
California Institute for Regenerative Medicine (CIRM)
Investigators
Layout table for investigator information
Study Director: Martin Lotz, MD Calibr, a division of Scripps Research
  Study Documents (Full-Text)

Documents provided by Calibr, a division of Scripps Research:
Study Protocol  [PDF] April 2, 2020
Statistical Analysis Plan  [PDF] May 15, 2020

Layout table for additonal information
Responsible Party: Calibr, a division of Scripps Research
ClinicalTrials.gov Identifier: NCT03133676    
Other Study ID Numbers: CBR-KA34-3001
First Posted: April 28, 2017    Key Record Dates
Results First Posted: May 17, 2021
Last Update Posted: October 27, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Calibr, a division of Scripps Research:
Osteoarthritis
Arthritis
Joint Disease
Osteoarthritis, Knee
Additional relevant MeSH terms:
Layout table for MeSH terms
Osteoarthritis
Osteoarthritis, Knee
Arthritis
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases