Overview

Phase III Study to Evaluate Safety and Effectiveness of NOVOCART 3D Plus vs. Microfracture in Knee Cartilage Defects

Status:
Active, not recruiting
Trial end date:
2023-06-01
Target enrollment:
0
Participant gender:
All
Summary
In this phase 3 clinical trial, a second generation ACI (autologous chondrocyte implantation technique) is compared to standard of care therapy (microfracture) to treat traumatic cartilage defects of the knee for efficacy and safety. The investigated study treatment NOVOCART 3D plus is a biphasic biological scaffold which contains cultivated chondrocytes derived from the patient in a previous tissue harvest procedure. Allocation to the study treatment is done by randomization in a ration of 2:1 in favor to ACI (investigational product). Follow-up data for efficacy is collected for 2 years: follow-up visits are performed 6 weeks, 3 months, 6 months, 12 months, 18 months and 24 months after treatment; additional data for safety will be collected for up to 5 years: 36, 48, and 60 months after treatment. The study involves knee surgery (by arthroscopy, or mini-arthrotomically for implantation surgery), and blood withdrawal for safety within the first year after treatment. Initial imaging is required at baseline. Optional MRI imaging and biomarker collection is done as substudy at specific sites only.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Tetec AG
Criteria
Inclusion Criteria:

1. Patient is between 18 and 65 years old at screening OR (in selected countries only) is
a pediatric patient (14-17 years old) with closed epiphyseal growth plate
(confirmation of closure of epiphyseal growth plate of the index knee by x-ray or MRI
required).

2. Patient has a localized articular cartilage defect of the femoral condyle or the
trochlea of the knee. 2 localized cartilage defects are accepted if the total defect
size is ≤ 6 cm2 and the size of each individual lesion is ≥ 2 cm2, both cartilage
defects are located at the femoral condyle and/or the trochlea and both cartilage
defects are to be treated with NOVOCART 3D plus or microfracture.

3. Patient has a defect size is between 2 and 6 cm2. Note: defect size can be estimated
by MRI at visit 1 if no data is available from medical history.

4. Patient has an intact articulating joint surface (not higher than Grade 2
International Cartilage Repair Society classification, no kissing lesions). Note: ICRS
classification can be estimated by MRI at visit 1 if no data is available from medical
history.

5. Patient has an intact meniscus; a maximum of 50% resection is allowed. Note: status of
meniscus can be estimated at visit 1 if no data is available from medical history.

6. Patient has a stable knee joint or sufficiently reconstructed ligaments. If not,
ligament repair must be done before, during or within 6 weeks after cartilage
treatment (ACT/microfracture).

7. Patient has free range of motion of the affected knee joint or ≤ 10° of extension and
flexion loss.

8. Patient has a defect-grade of III or IV according to the ICRS classification. Note:
ICRS classification can be estimated by MRI at visit 1 if not data is available from
medical history.

9. Patient has a baseline score of 60/100 on the 2000 International Knee Documentation
Committee (IKDC) subjective knee evaluation.

10. Patient is willing and able to give written informed consent to participate in the
study and to comply with all study requirements, including attending all follow-up
visits and assessments and postoperative rehabilitation regimen.

11. Mandatory for France only: Patient benefits of a health insurance regimen.

Exclusion Criteria (pre-operative):

1. Patient is the investigator or any subinvestigator, research assistant, pharmacist,
study coordinator, other staff or relative thereof directly involved in the conduct of
the study.

2. Patient is unable to undergo magnetic resonance imaging (MRI).

3. Patient has prior surgical treatment of the target knee using mosaicplasty, autologous
chondrocyte transplantation and/or microfracture. Note: prior diagnostic arthroscopies
with debridement and lavage are acceptable. Ligament repair is accepted, if performed
before, during or within 6 weeks after cartilage treatment (ACT/microfracture).

4. Patient has radiologically apparent degenerative joint disease in the target knee as
determined by Kellgren and Lawrence grade > 2 (see Appendix A).

5. Patient has chronic inflammatory arthritis and/or infectious arthritis.

6. Patient has joint space narrowing > 1/3 in the target knee when compared to the other
knee or smaller than 3 mm joint space measured on x-ray.

7. Patient has malalignment (valgus- or varus-deformity) in the target knee. Note: In
suspected cases, the mechanical axis must be established radiographically by complete
leg imaging in standing position and in a.p. or rather p.a. projection. The Mikulicz
line is not allowed to deviate more than 5 mm of the eminentia intercondylaris. If
alignment is necessary, surgery has to be performed before, during or within 6 weeks
after cartilage treatment (ACT/microfracture).

8. Patient has prior surgical treatment of clinical relevance of the target knee.

9. Patient has an osteochondral defect.

10. Patient has bilateral lower limb pain or low back pain.

11. Patient has a known systemic connective tissue disease.

12. Patient has a current uncontrolled diabetes.

13. Patient has a known history of autoimmune disease.

14. Patient has a known history of immunological suppressive disorder or is taking
immunosuppressants.

15. Patient is currently systemically or intra-articularly taking steroids and/or has used
steroids within the last 30 days prior to screening visit 1.

16. The patient has a history of HIV/AIDS.

17. The patient has a history of syphilis (Treponema pallidum).

18. The patient has an active hepatitis B or C infection with verified antigens. Note:
Patients with a cured hepatitis B or C infection and/or verified antibodies are not
excluded.

19. The patient has at the site of surgery an active systemic or local microbial
infection, eczematization or inflammable skin alterations (including protozoonosis:
Babesiosis, Trypanosomiasis (e.g. Chagas-Disease), Leishmaniasis, persistent bacterial
infections, like Brucellosis, spotted and typhus fever, other Rickettsiosis, Leprosy,
Recurrent Fever, Melioidosis or Tularaemia).

20. Patient has a known history of cancer within the past 5 years.

21. Patient has a known history of osteoporosis; also patients with primary
hyperparathyroidism or hyperthyroidism without satisfactory treatment, chronic renal
failure or patients with prior pathological fractures independent of the genesis are
excluded.

22. Patient has any degenerative muscular or neurological condition that would interfere
with evaluation of outcome measures including but not limited to Parkinson's disease,
amyotrophic lateral sclerosis (ALS), or multiple sclerosis (MS).

23. Patient has a body mass index (BMI) higher than 35 kg/m2.

24. Patient is a woman who is pregnant or lactating. Note: contraception is indicated for
female patients of childbearing potential until the day of cartilage treatment. Female
patients who are unwilling to practice a medically acceptable method of birth control
until the day of cartilage treatment cannot be included.

25. Patient is currently participating, or has participated in any other clinical study
within 3 months prior to the screening visit.

26. Patient has known current or recent history of illicit drug or alcohol abuse or
dependence

27. Patient has psychiatric or cognitive impairment that, in the opinion of the
investigator, would interfere with the patient's ability to comply with the study
requirements, e.g., Alzheimer's disease.

28. Patient has any other condition, which, in the opinion of the investigator, would make
the patient unsuitable for the study.

29. Patient has a history of HTLV.

Intra-operative Inclusion Criteria:

1. Patient is not pregnant as confirmed by urine pregnancy test before arthroscopy.

2. Patient has a localized articular cartilage defect of the femoral condyle or the
trochlea of the knee. 2 localized cartilage defects are accepted if the total defect
size is up to 6 cm2 and the size of each individual lesion is at least 2 cm2, both
cartilage defects are located at the femoral condyle and/or the trochlea and both
cartilage defects are to be treated with NOVOCART 3D plus or microfracture.

3. Patient has a defect size of 2 to 6 cm2 post-debridement.

4. Patient has an intact articulating joint surface (at least (or higher) Grade 2
International Cartilage Repair Society classification) no kissing lesions).

5. Patient has an intact meniscus; a maximum of 50% resection is allowed (no indication
for concurrent meniscus transplant).

6. Patient has a stable knee joint or sufficiently reconstructed ligaments. If not,
ligament repair must be done during or within 6 weeks after cartilage treatment
(ACT/microfracture).

7. Patient has a defect grade of III or IV according to the ICRS classification.