This pilot clinical trial has been designed to evaluate the safety and performance of the INSTRUCT scaffold, and to collect preliminary efficacy data
ID
Source
Brief title
Condition
- Bone and joint injuries
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The safety of the device will be evaluated looking at the incidence of :
- Device related adverse events during the healing period and up to 3 months
follow up
(Adverse device effects).
- Process related adverse events as observed intra-operatively and up to 3
months follow up
- Adverse events related to the surgical procedure specific to the device
implantation.
- Long term adverse device effects as observed from the period 3-24 months
Performance of the device has been defined as mechanical support of the
biodegradable PolyActive
scaffold observed as lesion filling at implantation shown by 3 months MRI,
compared to filling at
discharge.
Secondary outcome
Incidence of non-related treatment-emergent (serious) adverse events throughout
the 24 months of the
clinical investigation.
- Validation of timing of biopsy allowingpreliminary efficacy determination
- Preliminary efficacy:
o Improved KOOS, IKDC and painVAS scores
o Presence of cartilage formationas shown by biopsy at 6 or 12 months follow up
and by dGEMRIC MRI at 6, 12 and 24months follow-up
User handling feedback (complications and technical challenges):
- Ease of use of the device, instrumentation and process prior to and during
cell processing.
- Ease of use of device and instrumentation at implantation.
- Complaints (other than adverse events) and/or recommendations related to the
device, instrumentation and process.
Health economic data:
- Duration of the intra-operative procedure.
- Duration of hospital stay.
- Duration of rehabilitation program.
Background summary
This pilot clinical investigation is intended to provide sufficient data to
confirm that the INSTRUCT
therapy is safe and performs as a treatment for cartilage repair in view of
obtaining the CE-mark. The
clinical investigation will also provide on the first 10 subjects a subset data
on the validity of the timepoint
at which efficacy endpoints can be observed. The subject population included in
this nonrandomized
clinical investigation is not intended to provide statistically significant
data on efficacy but
will provide a preliminary confirmation on the clinical safety and performance
results prior to starting a
more extensive randomized clinical investigation to confirm longer term
efficacy data.
Study objective
This pilot clinical trial has been designed to evaluate the safety and
performance of the INSTRUCT scaffold, and to collect preliminary efficacy data
Study design
This multicenter, multinational non-randomized prospective interventional
feasibility clinical
investigation, shall be conducted in initially 2-3 (first 10 subjects) and
thereafter in 5-6 (subsequent 30
subjects) investigation sites in Europe.
This clinical investigation has been designed primarily to confirm safety and
performance of the device
to support design dossier approval in Europe. The safety and performance of the
material of the
INSTRUCT scaffold has been confirmed through extensive testing and a wide use
in the orthopaedic
area by Isotis* product Synplug. Synplug is also approved in the US through a
510K procedure for the
use of cement restriction. Hence, this clinical investigation is designed to
provide clinical data for the
use a specific autologous cell processing and seeding of cells on the
PolyActive scaffold as a
treatment for cartilage defects.
The first 3 subjects will undergo a biopsy at 6 month follow up to confirm
whether at this stage the
formation of hyaline-like cartilage can be observed. If the results of
histopathology are positive
meaning hyaline-like cartilage was observed, then the biopsy will continue to
be performed on the
remainder of the subjects at 6 months. Should histopathology fail to show
hyaline-like cartilage at 6
months then the biopsy for all subsequently enrolled subjects shall be
performed at 12 months follow
up. The first 3 subjects however will not undergo a second biopsy at 12 months
as part of this clinical
investigation.
After the treatment of the first 10 subjects a first safety interim observation
shall be performed. Upon
absence of serious adverse device effects during surgery, further enrolment of
additional 30 subjects
shall be performed in a larger number of investigation sites.
After 10 subjects have reached 3 months follow up, an interim analysis for
safety and performance
shall be performed
Intervention
During one surgical procedure, the following procedures take place: Bone marrow
biopsy, Cartilage biopsy, blood sample,
implantation of scaffold with cells.
Study burden and risks
Most of the risks associated with the INSTRUCT scaffold and procedure are those
associated with any surgical procedure or with alternative cartilage repair
therapies.
Some adverse events of interest have been identified and will be reported in an
expedite way during the study (similarly to SAEs) : surgical site inflammation,
surgical site infection, foreign body response, migration or dislocation of the
scaffold, graft delamination, haemarthrosis and knee locking. More details
can be found in section 16.4 of the Clinical Investigation Plan.
A process and product risk analysis according to ISO 14971 Application of risk
management to medical devices has been conducted. Risks have been proven
minimized or eliminated through appropriate design control, confirmed by
pre-clinical bench, laboratory and animal testing. This pilot clinical
investigation is conducted to make final conclusions about the safety of the
device and its related processes.
The following benefits are expected from the INSTRUCT treatment:
• Reduced pain after the surgery
• Improved mobility
• Reduced need for additional knee surgeries
• Reduced cartilage damage and development of osteoarthritis.
Prof.Bronkhorstlaan 10
3723 MB Bilthoven
Nederland
Prof.Bronkhorstlaan 10
3723 MB Bilthoven
Nederland
Listed location countries
Age
Inclusion criteria
1. Subjects aged 18-50 years old, (skeletally
mature as shown by epiphyseal plate).
2. Subject is able/willing to provide written
informed consent and willing to comply
with all pre-per and post operative clinical
investigation requirements.
3. Subjects presenting a single symptomatic
unilateral knee traumatic cartilage lesion
of the femoral condyle grade III to IV
(Outerbridge grading system)a
4. Subjects with a single lesion of the
femoral condyle with dimension after
debridement between - 1 cm2 and - 2.6
cm2. (length/diameter of the lesion
between 1.3 cm and 1.8 cm)
5. Subjects agree to participate in a strict rehabilitation
protocol and follow-up.
Exclusion criteria
1. Subjects who are participating in any
concurrent investigation.
2. Subjects with presence of more than one
clinically relevant cartilage lesion on the
femoral condyle.
3. Subjects with presence of a clinically
relevant cartilage lesion on the patella.
4. Female subjects who are pregnant or
lactating at baseline, or female subjects
who plan to become pregnant during the
course of the study.
5. Subject is presenting with any knee
defect on the other leg which may
interfere with the post operative
rehabilitation process.
6. Subjects with varus or valgus malalignment
exceeding 5°
7. Subjects with ligamentous instability of
the knee unless resolved by
reconstruction of the cruciate-ligaments
within the 6 months prior to enrolment.
8. Subjects with a history of autoimmune
disease.
9. Subjects suffering from advanced
osteoarthritis, rheumatoid arthritis, gout or
recurrent episodes of pseudo-gout, septic
arthritis, inflammatory joint disease, Paget
disease of bone, ochronosis, acromegaly,
hematochromatosis, Wilson disease,
primary osteochondromatosis, heritable
disorders, collagen gene mutations.
10. Subjects suffering from osteomyelitis.
11. Subjects who have undergone a meniscal
transplant.
12. Subjects with a present (or previous if not
resorbed) meniscal suture
13. Subjects who underwent any surgery or
other local treatment to the affected knee
within the past 6 months, other than
specified in exclusion criterion 7.
14. Subjects who underwent a meniscal
resection resulting in remaining lateral
and medial meniscal tissue volume of <
50%.
15. Subjects with tibial defects.
16. Subjects who received hyaluronic acid
intra-articular injections into the affected
knee within the past 6 months prior to
enrolment.
17. Subjects who received corticosteroid
therapy either systemically (PO or IM) or
intra-articularly in the affected knee within
6 months prior to enrolment.
18. Subjects taking medications or having
treatments which are known to have an
effect on bone/cartilage formation such as
but not limited to chemotherapy and
immunosuppressive drugs.
19. Subjects with a known allergy to
penicillins, to gadolinium (or derived
contrast agents) or multiple severe
allergies.
20. Subjects suffering from obesity (body
mass index of >30).
21. Subjects with vascular or neurological
disease affecting lower limbs.
22. Subjects with uncontrollable diabetes
23. Subjects with chronic severe renal
insufficiency or with renal dysfunction
24. Subjects with a history of kidney disease
or kidney transplantation
25. Subjects suffering from painful or
disabling disease of the spine, hips or
lower limbs that could interfere with the
evaluation or rehabilitation of the target
knee.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT01041885 |
| CCMO | NL33221.094.10 |