Cartilage Injury of KneePhase 2NCT01689337
A Multicenter Trial of Sprifermin (AS902330 [Recombinant Human Fibroblast Growth Factor-18]) or Placebo After Microfracture Surgery for Cartilage Injury of the Knee
A Phase 2 study testing Sprifermin (AS902330) in people with Cartilage Injury of Knee, run by EMD Serono.
Trial summary
This is a Phase 2, double-blind, multicenter, randomized, placebo-controlled trial to evaluate the efficacy and safety of Sprifermin (AS902330) (recombinant human fibroblast growth factor-18 [rhFGF-18]) as an adjunct treatment to subjects following microfracture (MFx) surgery for cartilage injury of the knee. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Cartilage Injury of Knee
- What is being tested?
- Sprifermin (AS902330)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- No sites listed yet
- Study dates
- Apr 2013to Oct 2013
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Subjects with candidature for MFx surgery on the femoral articular surfaces (medial or lateral condyles or trochlear groove), with intact subchondral bone
- Subjects with moderate to severe pain in the target knee prior to surgery; average score greater than equal to (>=) 4.0 over 7 consecutive days on numeric rating scale of pain intensity (completed within 30 [+15] days before surgery)
- Intraoperative inclusion criteria: Subjects with 1 or 2 focal chondral lesions per target knee, where peripheral debridement to healthy cartilage results in all of the following:
- Each lesion has an area of >= 1 square centimeter (cm^2) and less than equal to (<=) 4 cm^2
- Each lesion is <= 6 millimeter (mm) in depth, as measured from the surrounding subchondral plate
- Arthroscopic confirmation that each non-osteochondritis dissecans (OCD) lesion is between International Cartilage Repair Society (ICRS) Grades I and III (D); a Grade III non-OCD lesion is equivalent to an Outerbridge Grade IV lesion with minimal subchondral bone loss
- Other protocol-defined inclusion criteria could apply
Who cannot join
- Subjects with prior marrow stimulation treatment of the target knee, that is, MFx, micro-drilling, abrasion chondroplasty or cartilage repair including, but not limited to, autologous chondrocyte implantation (ACI), matrix/membrane autologous chondrocyte implantation (MACI), or osteochondral transplantation (autologous or allogeneic)
- Subjects with body mass index (BMI) of greater than 35 kilogram per square meter (kg/m^2) at screening
- Malalignment of the target knee greater than 5 degrees as measured from the mechanical axis, as confirmed by alignment (long bone) X-ray images
- Subjects with clinical and/or radiographic disease diagnosis of the target knee joint including, but not limited to the following: generalized osteoarthritis (OA), rheumatoid arthritis, or avascular necrosis
- Subjects who have any contraindication to MRI or gadolinium-based or iodinated contrast agents according to the site's standard practice guidelines
- Other protocol-defined exclusion criteria could apply
About this study
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase II Trial to Investigate the Efficacy and Safety of 30 mcg and 100 mcg AS902330 Given as One Cycle of Three Intra-articular Knee Injections Once a Week for Three Weeks as an Adjunct Treatment to Patients Following Microfracture Surgery for Cartilage Injury of the Knee.
This is a Phase 2, double-blind, multicenter, randomized, placebo-controlled trial to evaluate the efficacy and safety of Sprifermin (AS902330) (recombinant human fibroblast growth factor-18 [rhFGF-18]) as an adjunct treatment to subjects following microfracture (MFx) surgery for cartilage injury of the knee.
Primary Objectives
Read more
- To evaluate the effect of Sprifermin (AS902330) intra-articular knee injections as adjunct to microfracture (MFx) surgery on the composition of the refilled cartilage in the target knee, as measured by gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) time constant 1 (T1) relaxation time at 6 months after MFx surgery
- To evaluate the safety profile of Sprifermin (AS902330) when administered intra-articular into the knee as adjunct to MFx surgery in subjects with cartilage injury of the knee
Secondary Objectives
- To further support the efficacy and safety of Sprifermin (AS902330) as an adjunct to MFx for cartilage injury repair through symptomatic outcomes and quantitative MRI measurement
- Conditions
- Cartilage Injury of Knee
- Being tested
- Sprifermin (AS902330), Placebo
- Keywords
- Microfracture surgery, Cartilage repair, Knee surgery
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sprifermin (AS902330)Drug
Sprifermin (AS902330) will be administered at a dose of 30 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.
Sprifermin (AS902330)Drug
Sprifermin (AS902330) will be administered at a dose of 100 mcg as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.
PlaceboDrug
Placebo matched to Sprifermin (AS902330) will be administered as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery.
| Study group | Role | What they receive |
|---|---|---|
| Sprifermin (AS902330), 30 mcg | Experimental | Not described Receives: Drug: Sprifermin (AS902330) |
| Sprifermin (AS902330), 100 mcg | Experimental | Not described Receives: Drug: Sprifermin (AS902330) |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composition of the Refilled Cartilage Measured by Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) Using T1 Relaxation Time at Month 6 Post-MFx Surgery
The dGEMRIC is an imaging technique that estimates the proteoglycan (and glycosaminoglycan) content of joint cartilage using spin-lattice relaxation time T1 after penetration of gadolinium contrast agent. Composition of the refilled cartilage was to be reported.
Measured: 6 months post-MFx surgery
Secondary outcomes (11)
Composition of the Refilled Cartilage Measured by dGEMRIC Using T1 Relaxation Time Beyond Month 6 Post-MFx Surgery
The dGEMRIC is an imaging technique that estimates the proteoglycan (and glycosaminoglycan) content of joint cartilage using spin-lattice relaxation time T1 after penetration of gadolinium contrast agent. Composition of the refilled cartilage was to be reported.
Measured: Every 6 months up to 5 years beyond 6 months post-MFx surgery
Change From Baseline in Participant-reported Outcome Measure: Knee Injury and Osteoarthritis Outcome Score (KOOS) Sub-scores for Pain and Activities of Daily Living (ADL)
The KOOS Version LK1.0 is a knee-specific self-administered questionnaire used to assess pain, function, quality of life, and ADL. It consists of 42 items grouped into 5 subscales: pain, other symptoms (including swelling, restricted range of motion, and mechanical symptoms), function in ADL, function in sport and recreation (FSR), and impact on quality of life (QOL) (knee-related QOL, including awareness of the knee condition and changes in lifestyle). The subscales are scored separately; each yields a score between 0 and 100, with 0 representing extreme knee problems and 100 representing absence of problems. Total KOOS score is the average of all 5 subscale scores; ranging from 0 to 100; where 0 represents extreme knee problems and 100 represents absence of knee problems. Change from baseline in pain and ADL sub-scores was to be calculated by the respective scores at the specific time point minus the scores at baseline.
Measured: Every 6 months up to 5 years
Change From Baseline in Participant-reported Outcome Measure: Total KOOS Score, Three KOOS Sub-scores and Total KOOS Minus FSR Sub-score
The KOOS Version LK1.0 is a knee-specific self-administered questionnaire used to assess pain, function, quality of life, and ADL. It consists of 42 items grouped into 5 subscales: pain, other symptoms (including swelling, restricted range of motion, and mechanical symptoms), function in ADL, FSR, and impact on QOL (knee-related QOL, including awareness of the knee condition and changes in lifestyle). The subscales are scored separately; each yields a score between 0 and 100, with 0 representing extreme knee problems and 100 representing absence of problems. Total KOOS score is the average of all 5 subscale scores; ranging from 0 to 100; where 0 represents extreme knee problems and 100 represents absence of knee problems. Change from baseline in total KOOS score; other symptoms, knee-related QOL, and FSR sub-scores; and total KOOS minus FSR sub-score was to be calculated by the respective scores at the specific time point minus the scores at baseline.
Measured: Every 6 months up to 5 years
Change From Baseline in Participant-reported Outcome Measure: Numeric Rating Scale (NRS) Score
Knee pain was to be rated by the participant using an 11-point NRS of pain intensity. The NRS is scaled from 0 (no pain) to 10 (worst possible pain). Change from baseline in NRS score was to be calculated by the score at the specific time point minus the score at baseline.
Measured: Every 6 months up to 5 years
Change From Baseline in Participant-reported Outcome Measure: Lower Extremity Activity Scale (LEAS) Score
The LEAS is an 18-level single-question self-administered scale that has been validated as a clinical outcome measure for the assessment of participants' actual activity levels. The LEAS is scaled from 1 to 18, with 18 indicating levels of highest activity. Change from baseline in LEAS score was to be calculated by the score at the specific time point minus the score at baseline.
Measured: Every 6 months up to 5 years
Change From Baseline in the Physician-reported Outcome Measure: Lysholm Knee Scale Score
The Lysholm knee scale is a physician-reported outcome measure to assess knee function after ligament injury. It is scaled from 0 to 100 with higher scores representing better function. Change from baseline in Lysholm knee scale score was to be calculated by the score at the specific time point minus the score at baseline.
Measured: Every 6 months up to 5 years
Composition of the Refilled Cartilage Using T2 Mapping
The transverse relaxation time T2 mapping is an MRI technique that is able to evaluate collagen organization and orientation within cartilage. Composition of the refilled cartilage was to be reported.
Measured: Every 6 months up to 5 years
Volume of the Refilled Cartilage
Volume of the refilled cartilage was to be measured by MRI.
Measured: Every 6 months up to 5 years
Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) Score
The MOCART score is used to describe the constitution of the cartilage repair tissue and the surrounding structures.
Measured: Every 6 months up to 5 years
Six-minute Walk Test
Six (6)-minute walk test is used to measure gait function and for pre- and post-operative evaluation in cartilage injury repair. Maximum comfortable distance (in meters) that a participant can walk in 6 minutes was to be reported.
Measured: Every 3 months up to 5 years beyond Month 6 post-MFx surgery
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. An SAE is an AE that results in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect.
Measured: Baseline up to Month 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2012 (estimated)
- Study startApr 2013
- Primary completionOct 2013
- Study completionOct 2013
Why it stopped: The study was discontinued due to low recruitment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cartilage Injury of KneeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- EMD Serono
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01689337
- Sponsor's protocol ID
- EMR700692-007
- Other IDs
- 2012-001431-31
- Status last verified
- Jan 2017
- First submitted
- 17 Sep 2012
- Last updated
- 13 Jan 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase II Trial to Investigate the Efficacy and Safety of 30 mcg and 100 mcg AS902330 Given as One Cycle of Three Intra-articular Knee Injections Once a Week for Three Weeks as an Adjunct Treatment to Patients Following Microfracture Surgery for Cartilage Injury of the Knee.
- ClinicalTrials.gov ID
- NCT01689337
- Acronym / sponsor ID
- EMR700692-007
- Conditions
- Cartilage Injury of Knee
- Keywords
- Microfracture surgery, Cartilage repair, Knee surgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was discontinued due to low recruitment.
- Enrolment
- 1 participants (actual)
- Lead sponsor
- EMD SeronoIndustry (pharma, biotech, devices)
- Study start
- Apr 2013
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 21 Sep 2012 (estimated)
- Results
- Posted 31 Aug 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 2, double-blind, multicenter, randomized, placebo-controlled trial to evaluate the efficacy and safety of Sprifermin (AS902330) (recombinant human fibroblast growth factor-18 [rhFGF-18]) as an adjunct treatment to subjects following microfracture (MFx) surgery for cartilage injury of the knee.
Primary Objectives
- To evaluate the effect of Sprifermin (AS902330) intra-articular knee injections as adjunct to microfracture (MFx) surgery on the composition of the refilled cartilage in the target knee, as measured by gadolinium-enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) time constant 1 (T1) relaxation time at 6 months after MFx surgery
- To evaluate the safety profile of Sprifermin (AS902330) when administered intra-articular into the knee as adjunct to MFx surgery in subjects with cartilage injury of the knee
Secondary Objectives
- To further support the efficacy and safety of Sprifermin (AS902330) as an adjunct to MFx for cartilage injury repair through symptomatic outcomes and quantitative MRI measurement
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sprifermin (AS902330), 30 mcg | Experimental | Drug: Sprifermin (AS902330) |
| Sprifermin (AS902330), 100 mcg | Experimental | Drug: Sprifermin (AS902330) |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Subjects with candidature for MFx surgery on the femoral articular surfaces (medial or lateral condyles or trochlear groove), with intact subchondral bone
- Subjects with moderate to severe pain in the target knee prior to surgery; average score greater than equal to (>=) 4.0 over 7 consecutive days on numeric rating scale of pain intensity (completed within 30 [+15] days before surgery)
- Intraoperative inclusion criteria: Subjects with 1 or 2 focal chondral lesions per target knee, where peripheral debridement to healthy cartilage results in all of the following:
- Other protocol-defined inclusion criteria could apply
Key exclusion criteria (6 listed)
- Subjects with prior marrow stimulation treatment of the target knee, that is, MFx, micro-drilling, abrasion chondroplasty or cartilage repair including, but not limited to, autologous chondrocyte implantation (ACI), matrix/membrane autologous chondrocyte implantation (MACI), or osteochondral transplantation (autologous or allogeneic)
- Subjects with body mass index (BMI) of greater than 35 kilogram per square meter (kg/m^2) at screening
- Malalignment of the target knee greater than 5 degrees as measured from the mechanical axis, as confirmed by alignment (long bone) X-ray images
- Subjects with clinical and/or radiographic disease diagnosis of the target knee joint including, but not limited to the following: generalized osteoarthritis (OA), rheumatoid arthritis, or avascular necrosis
- Subjects who have any contraindication to MRI or gadolinium-based or iodinated contrast agents according to the site's standard practice guidelines
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sprifermin (AS902330)Sprifermin (AS902330) will be administered at a dose of 30 microgram (mcg) as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery. | Drug | Sprifermin (AS902330), 30 mcg |
| Sprifermin (AS902330)Sprifermin (AS902330) will be administered at a dose of 100 mcg as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery. | Drug | Sprifermin (AS902330), 100 mcg |
| PlaceboPlacebo matched to Sprifermin (AS902330) will be administered as intra-articular injection once every week for 3 weeks, starting from 2 weeks after MFx surgery. | Drug | Placebo |
Primary outcome
Composition of the Refilled Cartilage Measured by Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) Using T1 Relaxation Time at Month 6 Post-MFx Surgery
Time frame: 6 months post-MFx surgery
The dGEMRIC is an imaging technique that estimates the proteoglycan (and glycosaminoglycan) content of joint cartilage using spin-lattice relaxation time T1 after penetration of gadolinium contrast agent. Composition of the refilled cartilage was to be reported.
11 secondary outcomes
Composition of the Refilled Cartilage Measured by dGEMRIC Using T1 Relaxation Time Beyond Month 6 Post-MFx Surgery
Time frame: Every 6 months up to 5 years beyond 6 months post-MFx surgery
Change From Baseline in Participant-reported Outcome Measure: Knee Injury and Osteoarthritis Outcome Score (KOOS) Sub-scores for Pain and Activities of Daily Living (ADL)
Time frame: Every 6 months up to 5 years
Change From Baseline in Participant-reported Outcome Measure: Total KOOS Score, Three KOOS Sub-scores and Total KOOS Minus FSR Sub-score
Time frame: Every 6 months up to 5 years
Change From Baseline in Participant-reported Outcome Measure: Numeric Rating Scale (NRS) Score
Time frame: Every 6 months up to 5 years
Change From Baseline in Participant-reported Outcome Measure: Lower Extremity Activity Scale (LEAS) Score
Time frame: Every 6 months up to 5 years
Change From Baseline in the Physician-reported Outcome Measure: Lysholm Knee Scale Score
Time frame: Every 6 months up to 5 years
Composition of the Refilled Cartilage Using T2 Mapping
Time frame: Every 6 months up to 5 years
Volume of the Refilled Cartilage
Time frame: Every 6 months up to 5 years
Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) Score
Time frame: Every 6 months up to 5 years
Six-minute Walk Test
Time frame: Every 3 months up to 5 years beyond Month 6 post-MFx surgery
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: Baseline up to Month 60
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Cartilage Injury of Knee
RecruitingObservational study
Knee Cartilage Repair Registry
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Cartilage Injury
Recruiting
Impact of Bone-Marrow Aspirate Injections in Knee Arthroscopy
Chondral Lesion of the Knee, Meniscal Injuries
Recruiting
Effect of Platelet-rich Plasma (PRP) Injection on Knee Osteoarthritis
Platelets-rich Plasma, Osteoarthritis Knees Both
Enrolling by invitationObservational study
A Post Approval Multicenter 10 Year Follow-up Observational Trial of Marketed Product - MP01 vs. Surgical Standard of Care (SSOC) Used for the Treatment of Joint Surface Lesions of the Knee
Knee Injuries, Joint Surface Knee Lesions
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
EMD Serono, Inc., Rockland MA, a subsidiary of Merck KGaA, Darmstadt, Germany
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sprifermin (AS902330) in people with Cartilage Injury of Knee, run by EMD Serono.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Composition of the Refilled Cartilage Measured by Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage (dGEMRIC) Using T1 Relaxation Time at Month 6 Post-MFx Surgery (time frame: 6 months post-MFx surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2017.