Knee Osteoarthritis
Conditions
Keywords
OA, Knee OA, Liraglutide
Brief summary
This phase I study is a multicenter, randomized, double-blind, placebo-controlled study to assess the safety and tolerability of single ascending dose of IA 4P-004 in participants, * Between 18 and 80 years of age, * with target knee OA stage KL 2-4 A total of 32 participants will be enrolled in 4 cohorts, in each cohort participants will receive either 4P-004 or placebo (6:2).
Interventions
DRUG4P-004
single intraarticular administration in the knee joint
DRUGPlacebo
single intraarticular administration in the knee joint
Sponsors
4Moving Biotech
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Intervention model description
A total of 32 participants will be enrolled in 4 cohorts, in each cohort participants will receive either 4P-004 or placebo (6:2).
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participants who have the capacity to give informed consent and who are willing to comply with all study related procedures and assessments (consent via legally authorized representative will not be accepted), * Ambulatory participants, agreeing a 24-hour hospitalization, * Participants between 18 and 80 years of age, * Female participant of childbearing potential (WOCBP), must use contraceptive consistent with local regulations regarding the methods of contraception for those participating in clinical studies (see section 11.4) for at least 5 days following IMP injection, and must have a negative urine pregnancy test done within 24h before randomization, * Male participants (whose partners are of childbearing potential) must consent to use methods of contraception consistent with local regulations regarding the methods of contraception for those participating in clinical studies (see section 11.4), for at least 90 days following IMP injection, * Participants with knee osteoarthritis, KL 2-4 of their target knee (defined at screening as the knee with greater pain based on the participant's evaluation and the investigator's clinical judgment), * X-rays of the target knee within 6 months (if not, to be performed before randomization), * ECG within normal range, * WBC (white blood cell count) \> 3500/µL, * Hemoglobin \> 12 g/dL, * Platelets \> 100,000/ µL, * Creatinine clearance (CrCl) \> 60 mL/min, * Glycemia within normal range, * AST, ALT \< 1.5 upper limit of normal (ULN), * Amylasemia \< 1ULN, * Negative tests for COVID-19 (if required by the standard practice on site), HIV, HbsAg and hepatitis C Ab (Determination of HIV and hepatitis status can be based on participant-reported medical history, available medical records, and the most recently available laboratory results for the participant \[tests performed within the previous 12 months\]).
Exclusion criteria
* Breastfeeding women, * Treatment with systemic glucocorticoids greater than 10 mg prednisone or the equivalent per day within 4 weeks prior to screening, * Any treatment with glucosamine or chondroitin sulfate in the previous 3 months, * Any glucagon-like peptide 1 analogue hormones, * Anticoagulant treatment (current or within the last 10 days), * Treatment of the target knee with any IA injection (steroids, hyaluronic acid derivatives, PRP ….) within 3 months, * Knee surgery (of the target knee) performed within the previous 12 months or planned within the next 6 months, * Any partial knee replacement of the target knee, * Any known active infections or increased predisposition for the development of infections * Clinical signs and symptoms of active joint crystal disease, or any inflammatory joint disease, * Diabetes type I or II, * Congestive Heart Failure stage III or IV of NYHA classification, * Inflammatory bowel disease, * Any other chronic condition that has not been well controlled for a minimum of 3 months, * History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer) within the last 5 years, * Any condition, including laboratory findings, that in the opinion of the investigator constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct or evaluation, (for example, any abnormal reaction to previous IA injection), * Hypersensitivity to the active substance liraglutide or to any of the excipients: Disodium phosphate dihydrate, Propylene glycol, Phenol, * Participation in an interventional clinical research trial within 12 weeks prior.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | Day 1-Day 28 | Number of participants with Adverse Events, serious AEs (SAEs), with abnormal Vital signs, abnormal ECG reading and abnormal Laboratory test results |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Day 1 to Day 2 | Plasma concentration of liraglutide following a single IA injection at pre-injection (Time \[-4hours-0\]) and 2hours, 4hours, 8hours, 12hours, 16hours and 24-hours post injection. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory Biomarkers Identification | Day 1, Day 2, Day 8 | Serum and urine OA-related biomarkers (exploratory proteomic research of 4P-004 efficacy-related biomarkers) at Day 1 (Time \[-4-0\]hours, Time 8hours), Day 2 (Time 24hours) and Day 8. |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 4P-004 w mg 4P-004: single intraarticular administration in the knee joint Dose = w mg | 6 |
| 4P-004 x mg 4P-004: single intraarticular administration in the knee joint Dose = x mg | 6 |
| 4P-004 y mg 4P-004: single intraarticular administration in the knee joint Dose = y mg | 6 |
| 4P-004 z mg 4P-004: single intraarticular administration in the knee joint Dose = z mg | 8 |
| Placebo Placebo: single intraarticular administration in the knee joint | 8 |
| Total | 34 |
Baseline characteristics
| Characteristic | 4P-004 y mg | 4P-004 z mg | Placebo | Total | 4P-004 w mg | 4P-004 x mg |
|---|---|---|---|---|---|---|
| Age, Continuous | 60.3 years STANDARD_DEVIATION 8.5 | 59.1 years STANDARD_DEVIATION 59.5 | 63.5 years STANDARD_DEVIATION 11.5 | 60.1 years STANDARD_DEVIATION 9.1 | 62.5 years STANDARD_DEVIATION 6.9 | 54.2 years STANDARD_DEVIATION 5.3 |
| BMI | 28.5 kg/m2 STANDARD_DEVIATION 4.9 | 25.5 kg/m2 STANDARD_DEVIATION 5 | 29.5 kg/m2 STANDARD_DEVIATION 4.3 | 28.1 kg/m2 STANDARD_DEVIATION 5.1 | 29 kg/m2 STANDARD_DEVIATION 6.8 | 28 kg/m2 STANDARD_DEVIATION 5.1 |
| Kellgren-Lawrence score Kellgren-Lawrence 2 | 3 Participants | 6 Participants | 6 Participants | 21 Participants | 2 Participants | 4 Participants |
| Kellgren-Lawrence score Kellgren-Lawrence 3 | 3 Participants | 1 Participants | 2 Participants | 11 Participants | 4 Participants | 1 Participants |
| Kellgren-Lawrence score Kellgren-Lawrence 4 | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants |
| NRS | 3.5 units on a scale STANDARD_DEVIATION 2.6 | 3.5 units on a scale STANDARD_DEVIATION 2.3 | 3.7 units on a scale STANDARD_DEVIATION 2.4 | 3.7 units on a scale STANDARD_DEVIATION 2.2 | 3.8 units on a scale STANDARD_DEVIATION 2.3 | 4.0 units on a scale STANDARD_DEVIATION 2 |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants | — | — |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 5 Participants | 19 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 3 Participants | 15 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 8 | 0 / 8 |
| other Total, other adverse events | 5 / 6 | 5 / 6 | 5 / 6 | 6 / 8 | 6 / 8 |
| serious Total, serious adverse events | 0 / 6 | 0 / 6 | 1 / 6 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA.
Number of participants with Adverse Events, serious AEs (SAEs), with abnormal Vital signs, abnormal ECG reading and abnormal Laboratory test results
Time frame: Day 1-Day 28
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 4P-004 w mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | Abnormal Laboratory Value | 0 participants |
| 4P-004 w mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | TEAE | 5 participants |
| 4P-004 w mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | Abnormal ECG | 0 participants |
| 4P-004 w mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | SAE | 0 participants |
| 4P-004 w mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | Abnormal Vital Sign | 0 participants |
| 4P-004 x mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | Abnormal Laboratory Value | 0 participants |
| 4P-004 x mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | Abnormal Vital Sign | 0 participants |
| 4P-004 x mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | SAE | 0 participants |
| 4P-004 x mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | Abnormal ECG | 0 participants |
| 4P-004 x mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | TEAE | 5 participants |
| 4P-004 y mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | Abnormal Vital Sign | 0 participants |
| 4P-004 y mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | TEAE | 5 participants |
| 4P-004 y mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | SAE | 1 participants |
| 4P-004 y mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | Abnormal Laboratory Value | 0 participants |
| 4P-004 y mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | Abnormal ECG | 0 participants |
| 4P-004 z mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | Abnormal ECG | 0 participants |
| 4P-004 z mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | TEAE | 6 participants |
| 4P-004 z mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | Abnormal Laboratory Value | 0 participants |
| 4P-004 z mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | Abnormal Vital Sign | 0 participants |
| 4P-004 z mg | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | SAE | 0 participants |
| Placebo | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | Abnormal Vital Sign | 0 participants |
| Placebo | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | Abnormal Laboratory Value | 0 participants |
| Placebo | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | TEAE | 6 participants |
| Placebo | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | Abnormal ECG | 0 participants |
| Placebo | Safety and Tolerability of Single IA Administration of 4P-004 at Escalating Doses in Participants With Knee OA. | SAE | 0 participants |
Secondary
To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA
Plasma concentration of liraglutide following a single IA injection at pre-injection (Time \[-4hours-0\]) and 2hours, 4hours, 8hours, 12hours, 16hours and 24-hours post injection.
Time frame: Day 1 to Day 2
Population: Placebo participant where not included in the PK population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4P-004 w mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time [-4hours-0] | 0 ng/mL | Standard Deviation 0 |
| 4P-004 w mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 16 hours | 6.4 ng/mL | Standard Deviation 2.9 |
| 4P-004 w mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 12 hours | 7.1 ng/mL | Standard Deviation 3.1 |
| 4P-004 w mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 2 hours | 3.6 ng/mL | Standard Deviation 1.1 |
| 4P-004 w mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 24 hours | 5.0 ng/mL | Standard Deviation 2.4 |
| 4P-004 w mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 4 hours | 5.3 ng/mL | Standard Deviation 1.8 |
| 4P-004 w mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 8 hours | 7.3 ng/mL | Standard Deviation 3.1 |
| 4P-004 x mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 16 hours | 23.5 ng/mL | Standard Deviation 12 |
| 4P-004 x mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 8 hours | 23.2 ng/mL | Standard Deviation 12.4 |
| 4P-004 x mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 4 hours | 13.9 ng/mL | Standard Deviation 7.5 |
| 4P-004 x mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 12 hours | 24.5 ng/mL | Standard Deviation 12.9 |
| 4P-004 x mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 24 hours | 20.0 ng/mL | Standard Deviation 9.4 |
| 4P-004 x mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 2 hours | 7.2 ng/mL | Standard Deviation 4.2 |
| 4P-004 x mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time [-4hours-0] | 0 ng/mL | Standard Deviation 0 |
| 4P-004 y mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 8 hours | 123.7 ng/mL | Standard Deviation 74.9 |
| 4P-004 y mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time [-4hours-0] | 0 ng/mL | Standard Deviation 0 |
| 4P-004 y mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 2 hours | 58.1 ng/mL | Standard Deviation 38.8 |
| 4P-004 y mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 4 hours | 90.4 ng/mL | Standard Deviation 58.6 |
| 4P-004 y mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 12 hours | 122.2 ng/mL | Standard Deviation 69.2 |
| 4P-004 y mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 16 hours | 113.6 ng/mL | Standard Deviation 61.8 |
| 4P-004 y mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 24 hours | 95.2 ng/mL | Standard Deviation 52.1 |
| 4P-004 z mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 4 hours | 41.6 ng/mL | Standard Deviation 18.4 |
| 4P-004 z mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 24 hours | 53.6 ng/mL | Standard Deviation 25.4 |
| 4P-004 z mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 16 hours | 63.8 ng/mL | Standard Deviation 25.4 |
| 4P-004 z mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 2 hours | 24.6 ng/mL | Standard Deviation 15.7 |
| 4P-004 z mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time [-4hours-0] | 0 ng/mL | Standard Deviation 0 |
| 4P-004 z mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 12 hours | 67.2 ng/mL | Standard Deviation 24.7 |
| 4P-004 z mg | To Characterize the Plasma Concentration of Liraglutide When Administered as Single IA Doses at Escalating Dose Levels in Participants With Knee OA | Time 8 hours | 64.5 ng/mL | Standard Deviation 23 |
Other Pre-specified
Exploratory Biomarkers Identification
Serum and urine OA-related biomarkers (exploratory proteomic research of 4P-004 efficacy-related biomarkers) at Day 1 (Time \[-4-0\]hours, Time 8hours), Day 2 (Time 24hours) and Day 8.
Time frame: Day 1, Day 2, Day 8