FiH Safety and Feasibility Study Assessing Intra-articular Administration of AeGF in Patients with Knee Osteoarthritis

The company funding this study has developed an advanced therapy medicinal product (a cell therapy) from human donor cells which it wants to assess as a possible treatment for knee osteoarthritis (OA). Tissue from the gums of a human donor is used to make the study drug called allogeneic engineered Gingival Fibroblasts (aeGF). The purpose of this study is to evaluate the safety of a single injection of aeGF in the knee joint of participants with OA. aeGF have shown anti-inflammatory effects, pain relief and cartilage regeneration in animals and so are now being investigated as a treatment for OA in humans.

Scarcell Therapeutics SAS, has developed an advanced therapy medicinal product (a cell therapy) from human donor cells which will be assessed as a possible treatment for knee Osteoarthritis.

Tissue from the gums of a human donor is used to make the study drug called allogeneic engineered Gingival Fibroblasts (from now on aeGF). aeGF are defined as a Tissue Engineered Product (TEPs). TEPs contain cells or tissues that have been modified so that they can repair, regenerate or replace human tissue.

Preclinical studies have been completed which have shown promise in treating osteoarthritis in experimental animal models and domestic animals presenting with osteoarthritis. This study is intended to assess the safety of aeGF in humans for the first time.

In total 15 patients will be dosed with one intra-articular injection of aeGF into the knee, under ultrasound guidance .

The study duration is one year after the injection. A screening visit will take place prior to injection. Eligible participants will return for treatment with the study drug. Followed by a phone call post injection, up to a week later, to assess safety and any side effects of the injection. Hospital follow up visits will occur at 1, 3, 6 and 12 months post injection.

Eligibility Criteria:
Inclusion criteria:

1. Willing and able to provide informed consent;
2. Male or female participants aged ≥40 years;
3. Evidence of OA in the medial tibiofemoral joint (MTJ) as follows:

   * Clinical - knee pain;
   * Radiological - Kellgren-Lawrence:

     1. Grade 2 - definite osteophytes, possible joint space narrowing (JSN), or;
     2. Grade 3 - moderate osteophytes, definite JSN, some sclerosis, possible bone-end deformity (Altman et al., 1986; Kellgren et al., 1957; Kohn et al., 2016).
     3. Minimal joint space width (JSW) of 2.5 mm on knee X-ray (OARSI 1 or 2);
4. Score ≥3 on visual analogue scale (VAS) (0-10 range) for pain at Screening.

Exclusion Criteria:

1. Grade 0, 1 or 4 on the Kellgren-Lawrence grading scale for the target knee:

   * Grade 0: No osteophyte or JSN;
   * Grade 1: Doubtful JSN and possible osteophytic lipping;
   * Grade 4: Large osteophytes, 'bone-on-bone' JSN, severe sclerosis, and definite deformity of bone ends;
2. Severe malalignment of \>10° varus or valgus.
3. OA secondary to joint dysplasia, aseptic osteonecrosis, acromegaly, Paget's disease, Ehlers-Danlos Syndrome, Gaucher's disease, Stickler's syndrome, joint infection, haemophilia, haemochromatosis, calcium pyrophosphate deposition disease, neuropathic arthropathy, trauma, rheumatoid arthritis, gout, psoriatic arthritis, autoimmune arthritis or spondylitis;
4. Receipt of any IMP or any experimental therapeutic procedure in the 3 months or 5 half-lives before Screening, whichever is longer;
5. Taking corticosteroids or any immunosuppressants, e.g., cyclosporine, prior to Screening;
6. IA treatment with steroids or hyaluronic acid derivatives in the 3 months before Day 1;
7. Planned major surgery, e.g., joint replacement, within 2 months after IA injection;
8. Previous surgery on the target knee including diagnostic arthroscopy;
9. Lesions at the planned injection site that would present a contraindication to local injection of the study drug, e.g., open wounds, psoriatic lesions or infections of the skin;
10. Any known active infection;
11. Clinically significant abnormal haematology or biochemistry values (platelets, haemoglobin, leukocytes, alkaline phosphatase, AST, ALT, blood creatinine, bilirubin) at Screening;
12. Known or suspected infection with HTLV, HIV, Hepatitis B or C;
13. History of sarcoma;
14. History of cancer within five years, except treated basal cell and squamous cell carcinoma of the skin;
15. Women of childbearing potential who do not agree to use a highly effective contraceptive measure (see Section 8.4.5.1);
16. Current drug or alcohol abuse;
17. Contraindication to receiving a gadolinium contrast-enhanced MRI of the target knee (metallic implants, claustrophobia, previous anaphylactic reaction to gadolinium, eGFR \<30 mL/min/1.73 m2, acutely deteriorating renal function) or is unwilling to have MRI performed;
18. Participants with subchondral insufficiency fracture, osteonecrosis, acute or subacute fracture, acute bone contusion, pathologic fracture, stress fracture, fragmentation of articular bone, bone or soft tissue tumour, bone marrow infiltration, posterior meniscal root tear, rheumatoid arthritis, gout based on X-ray or MRI reading;
19. Participants who, in the Investigator's opinion, are unsuitable or unlikely to comply with the study procedures.