Clinical Study to Evaluate the Effectiveness and Safety of NTC chondrograft® versus the Standard Procedure Arthroscopic Microfracture as the Standard Procedure in the Treatment of Symptomatic Articular Cartilage Defects of the Knee

Phase 1

• Conditions: Symptomatic knee articular cartilage defects; Therapeutic area: Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutic techniques [E02]

• Registration Number: EUCTR2017-002601-35-CZ
• Lead Sponsor: PrimeCell Advanced Therapy a.s.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-11-15
• Last Update Posted: 8 June 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 214

Inclusion Criteria

The patients eligible for this study must fulfill the following criteria at the screening visit:
1.Patient is willing and able to give written informed consent to participate in the study and to actively participate in a follow-up program and designed rehabilitation regimen.
2.Patient is 18 = and = 55 years old at the screening.
3.Patient suffers from symptomatic knee disease with pain subscale score of < 55 at the KOOS rating scale
4.Duration of symptoms less than 3 years
5.Female patients must agree to take efficient contraception measures to prevent pregnancy before implantation surgery and 3 months thereafter
6.Patient agrees to keep detailed daily records of analgesics intake and if possible, to interrupt the analgesics medication one week before each assessment by the KOOS scale.
7.Patient agrees with laboratory testing for HIV, hepatitis B, C and syphilis.
8.Patient agrees to arrive to the study visit and completion of questionnaires according to the plan of the study.
9.Patient is motivated and willing to comply with rigorous rehabilitation program.

B. Criteria checked in course of pre-treatment arthroscopy

To be randomized, the patients must meet the following criteria in course of the index arthroscopy:

1.The cartilage defects determined by knee arthroscopy prior to randomization, featuring:
?modified Outerbridge [ 20 ] Grade III or IV focal cartilage defect(s),
?location on the femoral condyles and/or the trochlea,
?Phase II: defect size > 4 cm2 = 6cm2 post-debridement for single defect
or
total defect size > 4 cm2 = 8 cm2 post-debridement for 2 to 3 distinct defects,
?Phase III: up to 3 defects with total defect size = 2 cm2 = 4 cm2 post-debridement (note: the upper limit of the defect size is driven by the efficacy boundaries of the comparator),
?osteochondritis dissecans lesions are included if the bone graft implantation is not requested,
?intact articulating joint surface (no kissing lesion”).

2.Patient has stable knee joint, i.e. anterior and posterior cruciate ligaments are free of laxity as well as stable and intact. If not, stability of the knee has to be
re-established. Ligament repair or reconstruction procedures are allowed concurrent with the treatment surgery.

3.Patient has intact meniscus or partial meniscus with minimally 50% of functional meniscus remaining. Meniscal repair or resection might be performed either prior to or concurrent with NTC chondrograft® implantation if the surgeon presumes that =50% of functional meniscus would remain after the corrective surgery

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 214
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients meeting any of the following criteria will not be eligible for the study treatment:
1.Patient is the investigator or any sub-investigator, study coordinator or other staff, or relative thereof directly involved in the study protocol conduction.
2.Patient who participates in concurrent trials or participated in previous trial within previous 3 months.
3.Patient is unable to undergo magnetic resonance imaging (MRI).
4.Woman who is pregnant or anticipating pregnancy within 3 months following implantation.
5.Patient with a history of surgical treatment of the target knee using mosaicoplasty of microfracture.
6.Patient with history of corrective osteotomy or plastic surgery of patella or crossed ligaments within the last 6 months before screening.
7.Patient who has radiological apparent degenerative joint disease in the target knee, Kellgren-Lawrence Grade 2, 3 or 4 [ 7 ].
8.Patient with instability of the knee unless it is solved concurrently with the treatment surgery.
9.Patient with total meniscectomy or meniscal allograft or meniscectomy removing >50% of the meniscus in the target knee.
10.Patient with valgus or varus deformity in the target knee. In suspected cases according to a standard X-ray of the affected knee in the supine position, a long X-ray picture in p.a. projection will be performed, and in case the axis deviation from the Mikulicz line is < 3°or >9°, the patient will not be included.
11.Patient with malalignment of patella.
12.Patient with history of chronic inflammatory arthritis or acute infectious arthritis (septic) or osteomyelitis of the target joint.
13.Patient with known systemic connective tissue disease or autoimmune disease.
14.Patient with any clinically significant or symptomatic vascular, muscular or neurologic disorder that would interfere with evaluation of the target knee (i.e. concomitant painful or disabling disease of the spine, hips, or lower limbs).
15.Patient with CRP = 10 mg/l and/or WBC = 10 x 109/l, WBC < 2 x 109/l; a re-screening is allowed if the cause of inflammation has been successfully treated.
16.Patient with prolonged corticosteroid, immunosuppressive therapy by systemic or intra-articular route within the last 6 month before screening.
17.Patient with hyaluronic acid intra-articular injections into the target knee within the last 6 months before screening.
18.Patient with positive serology results for human immunodeficiency virus, hepatitis B, C or syphilis.
19.Patient with local microbial infection, eczema or skin inflammation at the site of surgery.
20.Patient with cancer except of skin non-melanoma carcinoma.
21.Patient with hemorrhagic disease.
22.Patient with chronic use of anticoagulants.
23.Patient with poor general health conditions excluding possibility of arthroscopy, arthrotomy or any other procedure prescribed by the protocol of the study (i.e. scheduled rehabilitation plan etc.)
24.Patient's condition, mental or otherwise, which does not allow signature of informed consent, consistent follow-up, or compliance with any aspect of the study.
25.Patient is currently abusing drugs or alcohol or, in the opinion of the investigator, is at high risk of poor compliance.
26.Patient with Body Mass Index (BMI) >35 kg/m2.

B. Criteria checked in course of pre-treatment arthroscopy

Patients meeting any of the following criteria in course of the index arthroscopy are not eligible for randomization to study treatment:

1.Single defect size out o

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of this study is (1) to evaluate, in 18 – 55 years old patients suffering from symptomatic knee articular cartilage defects, whether the implantation of NTC chondrograft® (autologous chondrocytes fixed in fibrin based excipient) is clinically effective, and, if so, (2) whether it is superior to standard procedure, arthroscopic microfracture treatment;Secondary Objective: Not applicable;Primary end point(s): Co-primary endpoint, defined as absolute difference between the final (week 104) and baseline score in multivariate evaluation of Pain and Function-Activities of Daily Living subscales of KOOS.;Timepoint(s) of evaluation of this end point: Co-primary endpoint, defined as absolute difference between the final (week 104) and baseline score in multivariate evaluation of Pain and Function-Activities of Daily Living subscales of KOOS.