Safety, tolerability and pharmacokinetics of intra‐articular (IA) single ascending dose of 4P‐004 in patient with Kellgren and Lawrence grade 2 to 4 osteoarthritic (OA) knee

Overview

Sponsor-declared trial summary

Key facts

Sponsor

4moving Biotech

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

Trial duration

10 May 2023 → 31 Oct 2023

Decision date (initial)

2022-06-23

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

4Moving Biotech

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Pharmacokinetic

To characterize safety and tolerability of single IA administration of 4P-004 at escalating doses (0.3, 1.0, 3.0mg) in participants with knee OA,
To determine the maximum tolerated dose (MTD) defined by occurrence of Dose Limiting Toxicities (DLTs).

Secondary objectives 1

1. To characterize the plasma PK of liraglutide when administered as single IA doses at escalating dose levels in participants with knee OA.

Conditions and MedDRA coding

Knee osteoarthritis

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Federal Agency For Medicines And Health Products

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 16

1. 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)
2. Ambulatory participants, agreeing a 24-hour hospitalization
3. Participants between 18 and 80 years of age
4. 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
5. 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
6. 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)
7. X-ray of the target knee within 6 months (if not, to be performed before randomization)
8. ECG within normal range
9. WBC (white blood cell count) > 3.5/µL
10. Hemoglobin > 12 g/dL
11. Platelets > 100,000/ µL
12. Creatinine clearance (CrCl) > 60 mL/min
13. Glycemia within normal range
14. AST, ALT < 1.5 upper limit of normal (ULN)
15. Amylasemia < 1ULN
16. 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)

Exclusion criteria 18

1. Breastfeeding women
2. Treatment with systemic glucocorticoids greater than 10 mg prednisone or the equivalent per day within 4 weeks prior to screening
3. Any treatment with glucosamine or chondroitin sulfate in the previous 3 months
4. Any glucagon-like peptide 1 analogue hormones
5. Anticoagulant treatment (current or within the last 10 days)
6. Treatment of the target knee with any intra-articular injection (steroids, hyaluronic acid derivatives, PRP ….) within 3 months
7. Knee surgery (of the target knee) performed within the previous 12 months or planned within the next 6 months
8. Any partial knee replacement of the target knee
9. Any known active infections or increased predisposition for the development of infections
10. Clinical signs and symptoms of active joint crystal disease
11. Diabetes type I or II
12. Congestive Heart Failure stage III or IV of NYHA classification
13. Inflammatory bowel disease
14. Any other chronic condition that has not been well controlled for a minimum of 3 months
15. 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
16. 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)
17. Hypersensitivity to the active substance liraglutide or to any of the excipients: Disodium phosphate dihydrate, Propylene glycol, Phenol
18. Participation in an interventional clinical research trial within 12 weeks prior

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Number of Adverse events (AEs), serious AEs (SAEs) (Common Terminology Criteria Adverse Events [CTC-AE]) from ICF signature to D29, including target knee pain and tenderness, erythema, swelling, local pain at injection site.
2. Vital signs from D-7 to D8, ECG from D-7 to D1: Mean change, number of Potentially Clinically Significant Abnormality (PCSA), Percentage of participants with PCSA.
3. Laboratory changes (Red Blood Cells (RBC), White Blood Cells (WBC), Hemoglobin (Hb), platelets, alanine transaminase (ALT), aspartate transaminase (AST), glycemia, amylasemia, creatinin clearance) from D-7 to D8: Mean changes number of PCSA, Percentage of participants with PCSA.

Secondary endpoints 1

1. Plasma concentration of liraglutide following a single IA injection. PK samples: D1 preinjection (T0-15min) and 2, 4, 8, 12, 16 and 24 hours post injection. Plasma concentrations will be performed by C.RIS Pharma (Saint Malo, France).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

4moving Biotech

Sponsor organisation

4moving Biotech

Address

Campus De L'institut Pasteur De Lille, 1 Rue Du Professeur Calmette 1 Rue Du Professeur Calmette

City

Lille

Postcode

59800

Country

France

Scientific contact point

Organisation

4moving Biotech

Contact name

Francis Berenbaum

Public contact point

Organisation

4moving Biotech

Contact name

Francis Berenbaum

Third parties 1

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Temporary halts 1 · Art. 38 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 2 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications