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

Sponsor
Calibr, a division of Scripps Research (Other)
Overall Status
Completed
CT.gov ID
NCT03133676
Collaborator
California Institute for Regenerative Medicine (CIRM) (Other)
60
Enrollment
4
Locations
2
Arms
23.9
Actual Duration (Months)
15
Patients Per Site
0.6
Patients Per Site Per Month

Study Details

Study Description

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
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.

Study Design

Study Type:
Interventional
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 :
Apr 28, 2020
Actual Study Completion Date :
Apr 28, 2020

Arms and Interventions

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 Names:
  • KA-34

    		•
    Placebo Comparator: Placebo

    Placebo is the formulation for KA34.

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

    Outcome Measures

    Primary Outcome Measures

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    40 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Diablo Clinical Research Walnut Creek California United States 94598
    2 Clinical Research of West Florida Clearwater Florida United States 33765
    3 Bioclinica Research Orlando Florida United States 32806
    4 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

    • Study Director: Martin Lotz, MD, Calibr, a division of Scripps Research

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Calibr, a division of Scripps Research
    ClinicalTrials.gov Identifier:
    NCT03133676
    Other Study ID Numbers:
    • CBR-KA34-3001
    First Posted:
    Apr 28, 2017
    Last Update Posted:
    Oct 27, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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:
    Osteoarthritis
    Osteoarthritis, Knee

    Study Results

    Participant Flow

    Recruitment Details A total of 60 subjects were randomized to 1 of 7 cohorts to receive KA34 or placebo. In the single-ascending dose (SAD) part, 24 subjects were randomized to receive a single dose of KA34 or placebo in 1 of 4 cohorts. After a thorough review of the Day 29 safety data from the SAD cohorts by the blinded Data Safety Monitoring Board, 36 subjects were randomized in the multiple-ascending dose (MAD) part of the study to receive 4 weekly doses of KA34 or placebo in 1 of 3 cohorts.
    Pre-assignment Detail Subjects with a diagnosis of osteoarthritis (OA) of the knee as per the clinical and radiographic criteria of the American College of Rheumatology and joint pain with a visual analog scale score of ≥ 40 millimeters (mm) on a 100 mm scale on the index knee, determined by the Investigator at Screening were eligible to join the study.
    Arm/Group Title Placebo (SAD) Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD) Placebo (MAD) Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects randomized to Cohorts 1 - 4 in the SAD part of the study received single intra-articular (IA) injections of matching placebo in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 50 micrograms (µg) KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29. Subjects randomized to Cohorts 5 - 7 in the MAD part of the study received weekly IA injections of matching placebo in the affected knee for 4 weeks and were followed up until Day 180. Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    Period Title: Overall Study
    STARTED 6 3 3 6 6 9 9 9 9
    COMPLETED 6 3 3 6 6 9 9 9 9
    NOT COMPLETED 0 0 0 0 0 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Placebo (SAD) Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD) Placebo (MAD) Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD) Total
    Arm/Group Description Subjects randomized to Cohorts 1 - 4 in the SAD part of the study received single IA injections of matching placebo in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29. Subjects randomized to Cohorts 5 - 7 in the MAD part of the study received weekly IA injections of matching placebo in the affected knee for 4 weeks and were followed up until Day 180. Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Total of all reporting groups
    Overall Participants 6 3 3 6 6 9 9 9 9 60
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    4
    66.7%
    3
    100%
    2
    66.7%
    5
    83.3%
    3
    50%
    6
    66.7%
    5
    55.6%
    7
    77.8%
    4
    44.4%
    39
    65%
    >=65 years
    2
    33.3%
    0
    0%
    1
    33.3%
    1
    16.7%
    3
    50%
    3
    33.3%
    4
    44.4%
    2
    22.2%
    5
    55.6%
    21
    35%
    Sex: Female, Male (Count of Participants)
    Female
    5
    83.3%
    1
    33.3%
    2
    66.7%
    4
    66.7%
    4
    66.7%
    4
    44.4%
    5
    55.6%
    4
    44.4%
    4
    44.4%
    33
    55%
    Male
    1
    16.7%
    2
    66.7%
    1
    33.3%
    2
    33.3%
    2
    33.3%
    5
    55.6%
    4
    44.4%
    5
    55.6%
    5
    55.6%
    27
    45%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    22.2%
    0
    0%
    2
    22.2%
    4
    6.7%
    Not Hispanic or Latino
    6
    100%
    3
    100%
    3
    100%
    6
    100%
    6
    100%
    9
    100%
    7
    77.8%
    9
    100%
    7
    77.8%
    56
    93.3%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    1
    16.7%
    0
    0%
    0
    0%
    1
    11.1%
    0
    0%
    3
    5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    1
    33.3%
    2
    33.3%
    1
    16.7%
    4
    44.4%
    1
    11.1%
    2
    22.2%
    0
    0%
    11
    18.3%
    White
    6
    100%
    3
    100%
    1
    33.3%
    4
    66.7%
    4
    66.7%
    5
    55.6%
    8
    88.9%
    6
    66.7%
    9
    100%
    46
    76.7%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    6
    100%
    3
    100%
    3
    100%
    6
    100%
    6
    100%
    9
    100%
    9
    100%
    9
    100%
    9
    100%
    60
    100%
    Grade of Osteoarthritis (Kellgren and Lawrence radiological classification system) (Count of Participants)
    Grade 0
    0
    0%
    2
    66.7%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    3.3%
    Grade 1
    2
    33.3%
    0
    0%
    1
    33.3%
    4
    66.7%
    4
    66.7%
    4
    44.4%
    6
    66.7%
    3
    33.3%
    7
    77.8%
    31
    51.7%
    Grade 2
    4
    66.7%
    1
    33.3%
    2
    66.7%
    2
    33.3%
    2
    33.3%
    5
    55.6%
    3
    33.3%
    6
    66.7%
    2
    22.2%
    27
    45%
    Grade 3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Grade 4
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    Title SAD Part: Number of Subjects Who Experienced Treatment Emergent Adverse Events (TEAEs)
    Description 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.
    Time Frame Day 1 up to Day 29

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (SAD) Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD)
    Arm/Group Description Subjects randomized to Cohorts 1 - 4 in the SAD part of the study received single IA injections of matching placebo in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29.
    Measure Participants 6 3 3 6 6
    At least 1 TEAE
    1
    16.7%
    2
    66.7%
    1
    33.3%
    4
    66.7%
    1
    16.7%
    At least 1 related TEAE
    0
    0%
    0
    0%
    0
    0%
    2
    33.3%
    0
    0%
    At least 1 severe TEAE
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    At least 1 severe related TEAE
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    At least 1 SAE
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    TEAE leading to discontinuation
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    TEAE leading to death
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    TEAE with CTCAE grade >=3
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2. Primary Outcome
    Title MAD Part: Number of Subjects Who Experienced TEAEs
    Description 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.
    Time Frame Day 1 up to Day 180

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (MAD) Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects randomized to Cohorts 5 - 7 in the MAD part of the study received weekly IA injections of matching placebo in the affected knee for 4 weeks and were followed up until Day 180. Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    Measure Participants 9 9 9 9
    At least 1 TEAE
    7
    116.7%
    3
    100%
    6
    200%
    5
    83.3%
    At least 1 related TEAE
    4
    66.7%
    1
    33.3%
    1
    33.3%
    0
    0%
    At least 1 severe TEAE
    1
    16.7%
    0
    0%
    0
    0%
    0
    0%
    At least 1 severe related TEAE
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    At least 1 SAE
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    TEAE leading to discontinuation
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    TEAE leading to death
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    TEAE with CTCAE grade >=3
    1
    16.7%
    0
    0%
    0
    0%
    0
    0%
    3. Secondary Outcome
    Title SAD Part: Mean Change From Baseline in Hemoglobin at Day 8
    Description The mean changes from baseline at Day 8 in hemoglobin levels for subjects in the SAD part of the study are presented.
    Time Frame Baseline and Day 8

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (SAD) Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD)
    Arm/Group Description Subjects randomized to Cohorts 1 - 4 in the SAD part of the study received single IA injections of matching placebo in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29.
    Measure Participants 6 3 3 6 6
    Mean (Standard Deviation) [grams/deciliter (g/dL)]
    -0.12
    (0.58)
    0.77
    (2.12)
    -0.07
    (0.81)
    0.08
    (0.48)
    -0.32
    (0.50)
    4. Secondary Outcome
    Title MAD Part: Mean Change From Baseline in Hemoglobin at Day 180
    Description The mean changes from baseline at Day 180 in hemoglobin levels for subjects in the MAD part of the study are presented.
    Time Frame Baseline and Day 180

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (MAD) Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects randomized to Cohorts 5 - 7 in the MAD part of the study received weekly IA injections of matching placebo in the affected knee for 4 weeks and were followed up until Day 180. Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    Measure Participants 9 9 9 9
    Mean (Standard Deviation) [g/dL]
    0.36
    (1.21)
    -0.60
    (1.01)
    -0.48
    (1.29)
    -0.07
    (0.19)
    5. Secondary Outcome
    Title SAD Part: Mean Change From Baseline in Hematocrit at Day 8
    Description The mean changes from baseline at Day 8 in hematocrit levels for subjects in the SAD part of the study are presented.
    Time Frame Baseline and Day 8

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (SAD) Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD)
    Arm/Group Description Subjects randomized to Cohorts 1 - 4 in the SAD part of the study received single IA injections of matching placebo in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29.
    Measure Participants 6 3 3 6 6
    Mean (Standard Deviation) [volume % of red blood cells (RBCs)]
    -0.20
    (1.61)
    2.40
    (6.67)
    -0.37
    (2.70)
    0.12
    (1.33)
    -0.97
    (1.58)
    6. Secondary Outcome
    Title MAD Part: Mean Change From Baseline in Hematocrit at Day 180
    Description The mean changes from baseline at Day 180 in hematocrit levels for subjects in the MAD part of the study are presented.
    Time Frame Baseline and Day 180

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (MAD) Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects randomized to Cohorts 5 - 7 in the MAD part of the study received weekly IA injections of matching placebo in the affected knee for 4 weeks and were followed up until Day 180. Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    Measure Participants 9 9 9 9
    Mean (Standard Deviation) [volume % of RBCs]
    42.68
    (4.59)
    41.33
    (4.77)
    42.12
    (2.02)
    44.54
    (2.35)
    7. Secondary Outcome
    Title SAD Part: Mean Change From Baseline in Total Bilirubin and Creatinine at Day 8
    Description The mean changes from baseline at Day 8 in total bilirubin and creatinine for subjects in the SAD part of the study are presented.
    Time Frame Baseline and Day 8

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (SAD) Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD)
    Arm/Group Description Subjects randomized to Cohorts 1 - 4 in the SAD part of the study received single IA injections of matching placebo in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29.
    Measure Participants 6 3 3 6 6
    Total bilirubin
    0.023
    (0.416)
    0.053
    (0.137)
    -0.033
    (0.058)
    0.100
    (0.179)
    0.037
    (0.102)
    Creatinine
    -0.038
    (0.059)
    0.100
    (0.200)
    -0.063
    (0.012)
    -0.032
    (0.041)
    -0.117
    (0.215)
    8. Secondary Outcome
    Title MAD Part: Mean Change From Baseline in Total Bilirubin and Creatinine at Day 180
    Description The mean changes from baseline at Day 180 in total bilirubin and creatinine for subjects in the MAD part of the study are presented.
    Time Frame Baseline and Day 180

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (MAD) Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects randomized to Cohorts 5 - 7 in the MAD part of the study received weekly IA injections of matching placebo in the affected knee for 4 weeks and were followed up until Day 180. Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    Measure Participants 9 9 9 9
    Total bilirubin
    0.067
    (0.100)
    -0.051
    (0.153)
    -0.017
    (0.112)
    -0.043
    (0.264)
    Creatinine
    -0.038
    (0.100)
    -0.006
    (0.099)
    0.054
    (0.112)
    0.030
    (0.077)
    9. Secondary Outcome
    Title SAD Part: Mean Change From Baseline in Liver Enzymes at Day 8
    Description 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).
    Time Frame Baseline and Day 8

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (SAD) Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD)
    Arm/Group Description Subjects randomized to Cohorts 1 - 4 in the SAD part of the study received single IA injections of matching placebo in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29.
    Measure Participants 6 3 3 6 6
    ALP
    0.0
    (3.8)
    -7.7
    (14.2)
    3.7
    (7.0)
    0.0
    (4.5)
    4.0
    (11.7)
    ALT
    0.8
    (4.5)
    3.7
    (7.5)
    -0.3
    (1.5)
    -1.3
    (3.1)
    -2.2
    (4.3)
    AST
    -0.2
    (3.0)
    6.0
    (10.1)
    -2.7
    (1.5)
    -1.0
    (2.5)
    -1.2
    (3.5)
    10. Secondary Outcome
    Title MAD Part: Mean Change From Baseline in Liver Enzymes at Day 180
    Description 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.
    Time Frame Baseline and Day 180

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (MAD) Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects randomized to Cohorts 5 - 7 in the MAD part of the study received weekly IA injections of matching placebo in the affected knee for 4 weeks and were followed up until Day 180. Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    Measure Participants 9 9 9 9
    ALP
    -3.4
    (8.8)
    -0.2
    (11.6)
    -10.2
    (13.8)
    1.1
    (7.6)
    ALT
    2.1
    (3.9)
    -6.6
    (21.1)
    -3.8
    (8.3)
    0.3
    (3.3)
    AST
    0.7
    (3.2)
    -4.1
    (12.8)
    -1.1
    (5.8)
    -0.7
    (3.1)
    11. Secondary Outcome
    Title SAD Part: Mean Change From Baseline in Systolic and Diastolic Blood Pressure at Day 8
    Description 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.
    Time Frame Baseline and Day 8

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (SAD) Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD)
    Arm/Group Description Subjects randomized to Cohorts 1 - 4 in the SAD part of the study received single IA injections of matching placebo in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29.
    Measure Participants 6 3 3 6 6
    SBP
    -7.3
    (18.2)
    6.0
    (12.2)
    -11.3
    (6.7)
    7.8
    (10.9)
    3.7
    (8.8)
    DBP
    -2.0
    (8.3)
    0.3
    (10.6)
    -8.3
    (9.0)
    4.2
    (9.2)
    9.0
    (9.5)
    12. Secondary Outcome
    Title MAD Part: Mean Change From Baseline in SBP and DBP at Day 180
    Description The mean changes from baseline at Day 180 in SBP and DBP for subjects in the MAD part of the study are presented.
    Time Frame Baseline and Day 180

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (MAD) Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects randomized to Cohorts 5 - 7 in the MAD part of the study received weekly IA injections of matching placebo in the affected knee for 4 weeks and were followed up until Day 180. Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    Measure Participants 9 9 9 9
    SBP
    7.7
    (13.3)
    8.9
    (8.5)
    -2.1
    (15.3)
    -0.3
    (20.4)
    DBP
    6.6
    (10.3)
    1.7
    (8.5)
    -3.0
    (11.3)
    4.6
    (9.4)
    13. Secondary Outcome
    Title SAD Part: Mean Change From Baseline in the QTcF Interval at Day 8
    Description 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.
    Time Frame Baseline and Day 8

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (SAD) Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD)
    Arm/Group Description Subjects randomized to Cohorts 1 - 4 in the SAD part of the study received single IA injections of matching placebo in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29.
    Measure Participants 6 3 3 6 6
    Mean (Standard Deviation) [milliseconds (msec)]
    2.3
    (14.3)
    11.7
    (6.8)
    -3.7
    (14.8)
    -10.7
    (25.3)
    3.5
    (32.4)
    14. Secondary Outcome
    Title MAD Part: Mean Change From Baseline in the QTcF Interval at Day 180
    Description 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.
    Time Frame Baseline and Day 180

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (MAD) Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects randomized to Cohorts 5 - 7 in the MAD part of the study received weekly IA injections of matching placebo in the affected knee for 4 weeks and were followed up until Day 180. Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    Measure Participants 9 9 9 9
    Mean (Standard Deviation) [msec]
    3.9
    (13.5)
    1.9
    (10.1)
    -3.6
    (14.7)
    3.4
    (24.0)
    15. Secondary Outcome
    Title SAD Part: Number of Subjects With Injection Site TEAEs
    Description 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.
    Time Frame Baseline up to Day 29

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (SAD) Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD)
    Arm/Group Description Subjects randomized to Cohorts 1 - 4 in the SAD part of the study received single IA injections of matching placebo in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29.
    Measure Participants 6 3 3 6 6
    Injection site erythema
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    0
    0%
    Injection site hypersensitvity
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    16.7%
    Injection site inflammation
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Injection site joint discomfort
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Injection site joint inflammation
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Injection site joint pain
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Injection site joint swelling
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Injection site nodule
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Injection site pain
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Injection site swelling
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    16. Secondary Outcome
    Title MAD Part: Number of Subjects With Injection Site TEAEs
    Description 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.
    Time Frame Baseline up to Day 180

    Outcome Measure Data

    Analysis Population Description
    The safety analysis set consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (MAD) Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects randomized to Cohorts 5 - 7 in the MAD part of the study received weekly IA injections of matching placebo in the affected knee for 4 weeks and were followed up until Day 180. Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    Measure Participants 9 9 9 9
    Injection site erythema
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Injection site hypersensitivity
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Injection site inflammation
    1
    16.7%
    0
    0%
    0
    0%
    0
    0%
    Injection site joint discomfort
    1
    16.7%
    1
    33.3%
    1
    33.3%
    1
    16.7%
    Injection site joint inflammation
    0
    0%
    0
    0%
    1
    33.3%
    0
    0%
    Injection site joint pain
    2
    33.3%
    0
    0%
    2
    66.7%
    1
    16.7%
    Injection site joint swelling
    2
    33.3%
    0
    0%
    0
    0%
    0
    0%
    Injection site nodule
    1
    16.7%
    0
    0%
    0
    0%
    0
    0%
    Injection site pain
    1
    16.7%
    0
    0%
    1
    33.3%
    0
    0%
    Injection site swelling
    1
    16.7%
    0
    0%
    0
    0%
    0
    0%
    17. Secondary Outcome
    Title SAD Part: Mean Maximum Plasma Concentration (Cmax)
    Description 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.
    Time Frame Pre-dose up to 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all subjects who received KA34 and had at least 1 measured concentration at a scheduled PK time point after start of dosing without protocol violations or events with potential to affect the PK concentrations.
    Arm/Group Title Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD)
    Arm/Group Description Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29.
    Measure Participants 3 3 6 6
    Geometric Mean (Geometric Coefficient of Variation) [nanograms/milliliter (ng/mL)]
    0.8528
    (43.6)
    2.757
    (29.9)
    5.732
    (18.7)
    9.435
    (41.4)
    18. Secondary Outcome
    Title MAD Part: Mean Cmax
    Description 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.
    Time Frame Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all subjects who received KA34 and had at least 1 measured concentration at a scheduled PK time point after start of dosing without protocol violations or events with potential to affect the PK concentrations.
    Arm/Group Title Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    Measure Participants 9 9 9
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    2.536
    (33.7)
    4.807
    (26.7)
    10.67
    (40.3)
    19. Secondary Outcome
    Title SAD Part: Median Time to Maximum Observed Plasma Concentration (Tmax)
    Description 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.
    Time Frame Pre-dose up to 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all subjects who received KA34 and had at least 1 measured concentration at a scheduled PK time point after start of dosing without protocol violations or events with potential to affect the PK concentrations.
    Arm/Group Title Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD)
    Arm/Group Description Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29.
    Measure Participants 3 3 6 6
    Median (Full Range) [hours (h)]
    0.25
    0.50
    0.38
    0.30
    20. Secondary Outcome
    Title MAD Part: Median Tmax
    Description 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.
    Time Frame Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all subjects who received KA34 and had at least 1 measured concentration at a scheduled PK time point after start of dosing without protocol violations or events with potential to affect the PK concentrations.
    Arm/Group Title Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    Measure Participants 9 9 9
    Median (Full Range) [h]
    0.50
    0.30
    0.50
    21. Secondary Outcome
    Title SAD Part: Mean Area Under the Concentration-time Curve From Time 0 to Time of Last Quantifiable Concentration (AUC[0-t])
    Description 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.
    Time Frame Pre-dose up to 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all subjects who received KA34 and had at least 1 measured concentration at a scheduled PK time point after start of dosing without protocol violations or events with potential to affect the PK concentrations.
    Arm/Group Title Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD)
    Arm/Group Description Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29.
    Measure Participants 3 3 6 6
    Mean (Standard Deviation) [ng*h/mL]
    1.430
    (0.2128)
    4.473
    (2.555)
    9.933
    (2.382)
    15.73
    (2.515)
    22. Secondary Outcome
    Title MAD Part: Mean AUC(0-t)
    Description 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.
    Time Frame Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all subjects who received KA34 and had at least 1 measured concentration at a scheduled PK time point after start of dosing without protocol violations or events with potential to affect the PK concentrations.
    Arm/Group Title Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    Measure Participants 9 9 9
    Mean (Standard Deviation) [ng*h/mL]
    4.578
    (1.312)
    7.077
    (1.333)
    19.53
    (9.554)
    23. Secondary Outcome
    Title SAD Part: Mean Area Under the Concentration-time Curve From Time 0 Extrapolated to Infinite Time (AUC[0-inf])
    Description 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.
    Time Frame Pre-dose up to 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all subjects who received KA34 and had at least 1 measured concentration at a scheduled PK time point after start of dosing without protocol violations or events with potential to affect the PK concentrations. Mean data is presented for subjects with data available for the parameter estimation.
    Arm/Group Title Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD)
    Arm/Group Description Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29.
    Measure Participants 2 2 6 5
    Mean (Standard Deviation) [ng*h/mL]
    1.595
    (0.2333)
    5.425
    (3.953)
    11.09
    (2.940)
    17.34
    (3.626)
    24. Secondary Outcome
    Title MAD Part: Mean AUC(0-inf)
    Description 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.
    Time Frame Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all subjects who received KA34 and had at least 1 measured concentration at a scheduled PK time point after start of dosing without protocol violations or events with potential to affect the PK concentrations. Mean data is presented for subjects with data available for the parameter estimation.
    Arm/Group Title Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    Measure Participants 9 8 9
    Mean (Standard Deviation) [ng*h/mL]
    5.041
    (1.556)
    7.370
    (1.440)
    21.22
    (11.05)
    25. Secondary Outcome
    Title SAD Part: Mean Apparent Terminal Half-life (t1/2)
    Description 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.
    Time Frame Pre-dose up to 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all subjects who received KA34 and had at least 1 measured concentration at a scheduled PK time point after start of dosing without protocol violations or events with potential to affect the PK concentrations.
    Arm/Group Title Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD)
    Arm/Group Description Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29.
    Measure Participants 3 3 6 6
    Mean (Standard Deviation) [h]
    1.253
    (0.7117)
    1.420
    (0.7072)
    1.145
    (0.1666)
    1.222
    (0.4439)
    26. Secondary Outcome
    Title MAD Part: Mean t1/2
    Description 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.
    Time Frame Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all subjects who received KA34 and had at least 1 measured concentration at a scheduled PK time point after start of dosing without protocol violations or events with potential to affect the PK concentrations.
    Arm/Group Title Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    Measure Participants 9 9 9
    Mean (Standard Deviation) [h]
    1.072
    (0.2567)
    0.9997
    (0.2991)
    0.9286
    (0.3044)
    27. Secondary Outcome
    Title SAD Part: Mean Apparent Clearance (CL/F)
    Description 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.
    Time Frame Pre-dose up to 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all subjects who received KA34 and had at least 1 measured concentration at a scheduled PK time point after start of dosing without protocol violations or events with potential to affect the PK concentrations. Mean data is presented for subjects with data available for the parameter estimation.
    Arm/Group Title Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD)
    Arm/Group Description Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29.
    Measure Participants 2 2 6 5
    Mean (Standard Deviation) [L/h]
    31.70
    (4.667)
    25.10
    (18.24)
    19.22
    (5.466)
    23.92
    (5.157)
    28. Secondary Outcome
    Title MAD Part: Mean CL/F
    Description 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.
    Time Frame Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all subjects who received KA34 and had at least 1 measured concentration at a scheduled PK time point after start of dosing without protocol violations or events with potential to affect the PK concentrations. Mean data is presented for subjects with data available for the parameter estimation.
    Arm/Group Title Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    Measure Participants 9 8 9
    Mean (Standard Deviation) [L/h]
    21.43
    (6.182)
    28.11
    (5.695)
    23.85
    (11.95)
    29. Secondary Outcome
    Title SAD Part: Mean Apparent Volume of Distribution (Vz/F)
    Description 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.
    Time Frame Pre-dose up to 4 hours post-dose on Day 1

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all subjects who received KA34 and had at least 1 measured concentration at a scheduled PK time point after start of dosing without protocol violations or events with potential to affect the PK concentrations. Mean data is presented for subjects with data available for the parameter estimation.
    Arm/Group Title Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD)
    Arm/Group Description Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29.
    Measure Participants 2 2 6 5
    Mean (Standard Deviation) [L]
    38.25
    (0.4950)
    34.30
    (19.66)
    31.47
    (9.479)
    35.56
    (4.706)
    30. Secondary Outcome
    Title MAD Part: Mean Vz/F
    Description 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.
    Time Frame Pre-dose up to 4 hours post-dose on Day 1 and pre-dose on Days 8, 15, 22 and 29

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all subjects who received KA34 and had at least 1 measured concentration at a scheduled PK time point after start of dosing without protocol violations or events with potential to affect the PK concentrations. Mean data is presented for subjects with data available for the parameter estimation.
    Arm/Group Title Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    Measure Participants 9 8 9
    Mean (Standard Deviation) [L]
    32.51
    (10.19)
    37.98
    (13.46)
    30.00
    (13.38)

    Adverse Events

    Time Frame TEAEs were collected from time of first administration of IP (Day 1) up to 30 days after the last administration of IP (approximately 1 month for the SAD cohorts and approximately 6 months for the MAD cohorts).
    Adverse Event Reporting Description TEAEs are presented for the safety analysis set which consisted of all subjects who received at least 1 dose of IP and were analyzed according to treatment received.
    Arm/Group Title Placebo (SAD) Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD) Placebo (MAD) Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Arm/Group Description Subjects randomized to Cohorts 1 - 4 in the SAD part of the study received single IA injections of matching placebo in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 50 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 100 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 200 µg KA34 in the affected knee and were followed up until Day 29. Subjects received a single IA injection of 400 µg KA34 in the affected knee and were followed up until Day 29. Subjects randomized to Cohorts 5 - 7 in the MAD part of the study received weekly IA injections of matching placebo in the affected knee for 4 weeks and were followed up until Day 180. Subjects received IA injections of 100 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 200 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180. Subjects received IA injections of 400 µg KA34 in the affected knee once weekly for 4 weeks and were followed up until Day 180.
    All Cause Mortality
    Placebo (SAD) Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD) Placebo (MAD) Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Serious Adverse Events
    Placebo (SAD) Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD) Placebo (MAD) Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/6 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Vascular disorders
    Orthostatic hypotension 0/6 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Other (Not Including Serious) Adverse Events
    Placebo (SAD) Cohort 1: KA34 50 µg (SAD) Cohort 2: KA34 100 µg (SAD) Cohort 3: KA34 200 µg (SAD) Cohort 4: KA34 400 µg (SAD) Placebo (MAD) Cohort 5: KA34 100 µg (MAD) Cohort 6: KA34 200 µg (MAD) Cohort 7: KA34 400 µg (MAD)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/6 (16.7%) 2/3 (66.7%) 1/3 (33.3%) 4/6 (66.7%) 1/6 (16.7%) 7/9 (77.8%) 3/9 (33.3%) 6/9 (66.7%) 5/9 (55.6%)
    Cardiac disorders
    Left ventricular dysfunction 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Gastrointestinal disorders
    Diarrhoea 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 1/9 (11.1%)
    Intestinal mass 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 1/9 (11.1%)
    General disorders
    Injection site erythema 0/6 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Injection site hypersensitivity 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Peripheral swelling 0/6 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Injection site joint discomfort 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 1/9 (11.1%) 1/9 (11.1%) 1/9 (11.1%)
    Injection site joint pain 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 2/9 (22.2%) 0/9 (0%) 2/9 (22.2%) 1/9 (11.1%)
    Chills 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 1/9 (11.1%) 0/9 (0%)
    Injection site joint inflammation 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 1/9 (11.1%) 0/9 (0%)
    Injection site pain 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 1/9 (11.1%) 0/9 (0%)
    Injection site inflammation 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Injection site joint swelling 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 2/9 (22.2%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Injection site nodule 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Injection site swelling 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Infections and infestations
    Tooth abscess 0/6 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Urinary tract infection 0/6 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Diverticulitis 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 1/9 (11.1%) 0/9 (0%) 1/9 (11.1%)
    Nasopharyngitis 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 1/9 (11.1%)
    Rabies 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 1/9 (11.1%) 0/9 (0%)
    Cystitis 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Upper respiratory tract infection 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Viral infection 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Injury, poisoning and procedural complications
    Muscle strain 0/6 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Post procedural complication 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 1/6 (16.7%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Procedural pain 0/6 (0%) 1/3 (33.3%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Skin abrasion 0/6 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Animal bite 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 1/9 (11.1%) 0/9 (0%)
    Ligament rupture 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Meniscus injury 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Metabolism and nutrition disorders
    Hypercholesterolaemia 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%)
    Type 2 diabetes mellitus 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%)
    Glucose tolerance impaired 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Vitamin D deficiency 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Musculoskeletal and connective tissue disorders
    Joint swelling 0/6 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 1/9 (11.1%)
    Pain in extremity 0/6 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Musculoskeletal pain 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 1/9 (11.1%) 1/9 (11.1%) 1/9 (11.1%)
    Arthralgia 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 6/9 (66.7%) 1/9 (11.1%) 1/9 (11.1%) 0/9 (0%)
    Limb discomfort 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 1/9 (11.1%) 0/9 (0%) 1/9 (11.1%)
    Back pain 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 1/9 (11.1%) 0/9 (0%)
    Muscle spasms 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 2/9 (22.2%) 0/9 (0%) 0/9 (0%) 1/9 (11.1%)
    Arthritis 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Joint stiffness 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 2/9 (22.2%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Myalgia 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Osteoarthritis 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Nervous system disorders
    Headache 0/6 (0%) 0/3 (0%) 1/3 (33.3%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 1/9 (11.1%)
    Dizziness 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 1/9 (11.1%) 0/9 (0%)
    Sciatica 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 1/9 (11.1%) 0/9 (0%)
    Somnolence 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%)
    Tension headache 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%)
    Respiratory, thoracic and mediastinal disorders
    Asthma 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%)
    Skin and subcutaneous tissue disorders
    Rash 1/6 (16.7%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Dermatitis contact 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 1/9 (11.1%)
    Rash pruritic 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 1/9 (11.1%)
    Skin burning sensation 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Skin ulcer 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Vascular disorders
    Hypertension 0/6 (0%) 0/3 (0%) 0/3 (0%) 0/6 (0%) 0/6 (0%) 1/9 (11.1%) 0/9 (0%) 0/9 (0%) 0/9 (0%)
    Orthostatic hypotension 0/6 (0%) 0/3 (0%) 0/3 (0%) 1/6 (16.7%) 0/6 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%) 0/9 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Study Director
    Organization Calibr, a Division of Scripps Research
    Phone (858) 242 1000
    Email KA34ph1@scripps.edu
    Responsible Party:
    Calibr, a division of Scripps Research
    ClinicalTrials.gov Identifier:
    NCT03133676
    Other Study ID Numbers:
    • CBR-KA34-3001
    First Posted:
    Apr 28, 2017
    Last Update Posted:
    Oct 27, 2021
    Last Verified:
    Oct 1, 2021