Knee OsteoarthritisPhase 1NCT01033994
A Multicenter Study of rhFGF 18 in Patients With Knee Osteoarthritis Not Requiring Surgery
A Phase 1 study testing AS902330 in people with Knee Osteoarthritis, run by Merck KGaA, Darmstadt, Germany at 28 sites in 9 countries.
Trial summary
Osteoarthritis (OA) is one of the most common diseases affecting the joints, usually those that are weight bearing such as the knees. OA is considered to be a disease of the cartilage in the joints even though it involves the whole joint, including the bone and synovium (thin lining of the joints which produces… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Knee Osteoarthritis
- What is being tested?
- AS902330
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 192 participants
- Where
- 28 sitesin 9 countries
- Study dates
- Oct 2008to Dec 2010
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female >= 40 years of age; females must be postmenopausal or surgically sterile
- Established diagnosis of primary femoro-tibial OA of the target knee by standard American College of Rheumatology Criteria for at least six months (clinical AND radiological criteria)
- Radiological disease stage 2 or 3 (i.e., clear evidence of OA, but not most advanced disease) in the target knee according to the Kellgren-Lawrence grading of knee OA
- No major knee surgery (e.g., partial or total knee replacement, interventional arthroscopy) in the target knee planned for at least 12 months after first injection of the study drug
- Documented need for symptomatic PRN (as needed)-treatment for OA in the target knee with systemic non-steroidal anti-inflammatory drugs (NSAIDs) and/or other analgesics.
- Total WOMAC score between 24 and 72 (out of 96, corresponding to mild, moderate, or severe, but not extreme OA symptoms) for the target knee while on oral symptomatic treatment at baseline
- Full understanding of the requirements of the study and willingness to comply with all study visits and assessments
- Patients must have read and understood the informed consent form, and must have signed it prior to any study-related procedure
Who cannot join
- any condition, including laboratory findings and findings in the medical history or in the pre-study assessments, that in the opinion of the Investigator constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct or evaluation
- clinically significant abnormal hematology (hemoglobin, leucocytes, and platelets), or blood chemistry values (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, and creatinine
- receipt of any investigational product or any experimental therapeutic procedure within the last 12 weeks preceding screening
- participation in FIH study 27575 or in a different cohort of this study
- i.a. treatment of the target knee with steroids or hyaluronic acid derivatives within the 3 months before baseline
- for MAD cohorts, any contra-indications to MRI according to MRI guidelines
Show all 13Show fewer
- any condition that would interfere with efficacy or safety assessments in the target knee
- any drug or food supplement with potential disease-modifying effect (glucosamine, diacerin, chondroitin sulfate) unless given at a stable dose over at least 4 weeks prior to first injection
- use of electrotherapy or acupuncture for OA, unless there is a stable regimen for at least 4 weeks before baseline
- any known active infections, including suspicion of intra-articular infection and/or infections that may compromise the immune system such as HIV, Hepatitis B or Hepatitis C infection
- history of sarcoma and/or of other active malignancy within five years, except adequately treated basal cell or squamous cell carcinoma of the skin
- signs and symptoms suggestive of transmissible spongiform encephalopathy
- secondary osteoarthritis: e.g., joint dysplasias, aseptic osteonecrosis, acromegaly, Paget's disease, Ehlers-Danlos syndrome, Gaucher's disease, Stickler's syndrome, joint infection, hemophilia, hemochromatosis, calcium pyrophosphate deposition disease, or neuropathic arthropathy whatever the cause
Trial locations and contacts
28 sites in 9 countries.
28 sites in 9 countries
Canada6 sites
SKDS Research, Inc.
Newmarket
Kells Medical Research Group
Pointe-Claire
Centre de rhumatologie St-Louis
Québec
Groupe de Recherche en Maldies Osseuses de Quebec
Québec
London Road Diagnostic Clinic
Sarnia
Albion Finch Medical Centre
Toronto
Poland6 sites
NZOZ Centrum Medyczne Artur Racewicz
Bialystok
Krakowskie Centrum Medyczne NZOZ
Cracow
REUMED Sp. z o.o.,
Lublin
Niepubliczny Zaklad Opieki Zdrowotnej Nasz Lekarz
Torun
Centrum Leczenia Chorob Cywilizacyjnych
Warsaw
Centrum Medyczne OSTEOMED Sp. z o.o.
Warsaw
Croatia3 sites
Clinical hospital Split
Split
Clinical Hospital "Sestre Milosrdnice"
Zagreb
Polyclinic for internal medicine, gynecology, radiology, physical medicine and rehabilitation
Zagreb
Finland3 sites
Kuopio University Hospital, Department of Ortopaedics
Kuopio
Oulu University Hospital, Surgical and Intensive Care Division
Oulu
Turku University Central Hospital, Orthopedic Research Unit
Turku
Serbia3 sites
Clinical Hospital Center Bezanijska Kosa
Belgrade
Institute of Rheumatology Resavska 69
Belgrade
• Name: Institute of diagnostic, prevention and rechabilitation of cardiovascular and rheumatoid diseases
Niška Banja
South Africa3 sites
FARMOVS-PAREXEL (Pty) Ltd, University of the Free State
Bloemfontein, 9301
PAREXEL -George
George, 6529
PAREXEL-Port Elizabeth, Mercantile Hospital
Port Elizabeth, 6020
Sweden2 sites
Ortopediska mottagningen
Hässleholm
Kirurg- och ortopedkliniken Kungälvs sjukhus, 442 83 Kungälv
Kungälv
Bulgaria1 site
UMHAT "Sv. Ivan Rilski", Clinical Research Unit for Phase I
Sofia, 1612
About this study
Official title: A Randomized, Double Blind, Placebo-controlled, Multicenter, Single and Multiple Ascending Dose Study of AS902330 (rhFGF-18) Administered Intra-articularly in Patients With Primary Osteoarthritis of the Knee Who Are Not Expected to Require Knee Surgery Within One Year
Osteoarthritis (OA) is one of the most common diseases affecting the joints, usually those that are weight bearing such as the knees. OA is considered to be a disease of the cartilage in the joints even though it involves the whole joint, including the bone and synovium (thin lining of the joints which produces synovial fluid). With time, more and more of the cartilage is destroyed by the disease with inflammation commonly occurring.
AS902330 is expected to increase the production and development of specific bone cells: chondrocytes and osteoblasts (cells that produce and maintain bone and cartilage). This is expected to lead to repair and generation of the cartilage, and a narrowing of the space width between the knee joints in a selected region of the knee cartilage. The purpose of this study is to see how safe treatment with AS902330 is, and to evaluate its effect on the knee cartilage. In addition, the study will also measure the effects of AS902330 in the blood, which reflect disease activity.
- Conditions
- Knee Osteoarthritis
- Being tested
- AS902330
- Keywords
- Knee osteoarthritis, Fibroblast growth factor 18, Sprifermin
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AS902330Biological
Also called rhFGF 18, Recombinant human fibroblast growth factor 18, Sprifermin
10, 30 or 100 µg intra-articular injection per subject in the Single Ascending Dose (SAD) cohorts and 10, 30 or 100 µg intra-articular injection per week for three weeks per subject in the Multiple Ascending Dose (MAD) cohorts.
| Study group | Role | What they receive |
|---|---|---|
| AS902330 | Experimental | Not described Receives: Biological: AS902330 |
| Placebo | Placebo comparator | Not described Receives: Biological: AS902330 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in cartilage thickness in the medial femoro-tibial compartment of the target knee joint, assessed by MRI
Measured: 6 and 12 months after first injection
Nature, incidence and severity of local and systemic treatment-emergent adverse events (TEAEs)
Measured: MAD Cohorts: 1 year + 1 month; SAD Cohorts: 4 Weeks
Proportion of subjects experiencing AIRs defined as increase of pain by 30mm on a 100mm visual analogue scale (VAS) associated with a self-reported synovial fluid effusion within 3 days following i.a. injection
Measured: MAD Cohorts: Week 1, 2, 3, 13 14 and 15 (injections weeks); SAD Cohorts: Week 1
Laboratory assessments, including blood chemistry, hematology, urinalysis, and ECG
Measured: MAD Cohorts: Week 0, 4, 13, 17, 52; SAD Cohorts: Weeks 0 & 4
Secondary outcomes (10)
Change in cartilage thickness in the medial femoro-tibial compartment of the target knee joint, assessed by MRI
Measured: 52 Weeks
Change in total cartilage volume and thickness in the other compartments of the target knee joint, assessed by MRI
Measured: 52 Weeks
Change over time of structural as well as compositional parameters of the knee joint (e.g. cartilage and bone), evaluated by MRI
Measured: 52 Weeks
Change in WOMAC (Western Ontario MacMaster Osteoarthritis Questionaire) total score in the target knee from 5-point Likert scales
Measured: 52 Weeks
Change in WOMAC Function and Pain index scores in the target knee
Measured: 52 Weeks
Change in osteoarthritis (OA) pain in the target knee on a 100mm visual analogue scale (VAS)
Measured: 52 Weeks
Change in JSW in the target knee by x-ray
Measured: 52 Weeks
Presence of anti-AS902330 antibodies
Measured: 52 Weeks
Blood levels of AS902330
Measured: 52 Weeks
MRI at 3 months, score on WOMAC questionnaire at 3, 6 and 12 months.
Measured: 6 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2009 (estimated)
- Study startOct 2008
- Primary completionOct 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Knee OsteoarthritisStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Donatus Dreher, MD, PhD, Study director, Merck Serono S.A., Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01033994
- Sponsor's protocol ID
- 28980
- Status last verified
- Jun 2014
- First submitted
- 16 Dec 2009
- Last updated
- 25 Jun 2014
- Results posted
- No
Publications
Lohmander LS, Hellot S, Dreher D, Krantz EF, Kruger DS, Guermazi A, Eckstein F. Intraarticular sprifermin (recombinant human fibroblast growth factor 18) in knee osteoarthritis: a randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. 2014 Jul;66(7):1820-31. doi: 10.1002/art.38614.
PubMed 24740822Onuora S. Osteoarthritis: Sprifermin shows cartilage-protective effects in knee OA. Nat Rev Rheumatol. 2014 Jun;10(6):322. doi: 10.1038/nrrheum.2014.68. Epub 2014 May 6. No abstract available.
PubMed 24798571Roemer FW, Aydemir A, Lohmander S, Crema MD, Marra MD, Muurahainen N, Felson DT, Eckstein F, Guermazi A. Structural effects of sprifermin in knee osteoarthritis: a post-hoc analysis on cartilage and non-cartilaginous tissue alterations in a randomized controlled trial. BMC Musculoskelet Disord. 2016 Jul 9;17:267. doi: 10.1186/s12891-016-1128-2.
PubMed 27393009Eckstein F, Wirth W, Guermazi A, Maschek S, Aydemir A. Brief report: intraarticular sprifermin not only increases cartilage thickness, but also reduces cartilage loss: location-independent post hoc analysis using magnetic resonance imaging. Arthritis Rheumatol. 2015 Nov;67(11):2916-22. doi: 10.1002/art.39265.
PubMed 26138203
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind, Placebo-controlled, Multicenter, Single and Multiple Ascending Dose Study of AS902330 (rhFGF-18) Administered Intra-articularly in Patients With Primary Osteoarthritis of the Knee Who Are Not Expected to Require Knee Surgery Within One Year
- ClinicalTrials.gov ID
- NCT01033994
- Acronym / sponsor ID
- 28980
- Conditions
- Knee Osteoarthritis
- Keywords
- Knee osteoarthritis, Fibroblast growth factor 18, Sprifermin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Study start
- Oct 2008
- Primary completion
- Oct 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 17 Dec 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Osteoarthritis (OA) is one of the most common diseases affecting the joints, usually those that are weight bearing such as the knees. OA is considered to be a disease of the cartilage in the joints even though it involves the whole joint, including the bone and synovium (thin lining of the joints which produces synovial fluid). With time, more and more of the cartilage is destroyed by the disease with inflammation commonly occurring.
AS902330 is expected to increase the production and development of specific bone cells: chondrocytes and osteoblasts (cells that produce and maintain bone and cartilage). This is expected to lead to repair and generation of the cartilage, and a narrowing of the space width between the knee joints in a selected region of the knee cartilage. The purpose of this study is to see how safe treatment with AS902330 is, and to evaluate its effect on the knee cartilage. In addition, the study will also measure the effects of AS902330 in the blood, which reflect disease activity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AS902330 | Experimental | Biological: AS902330 |
| Placebo | Placebo comparator | Biological: AS902330 |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female >= 40 years of age; females must be postmenopausal or surgically sterile
- Established diagnosis of primary femoro-tibial OA of the target knee by standard American College of Rheumatology Criteria for at least six months (clinical AND radiological criteria)
- Radiological disease stage 2 or 3 (i.e., clear evidence of OA, but not most advanced disease) in the target knee according to the Kellgren-Lawrence grading of knee OA
- No major knee surgery (e.g., partial or total knee replacement, interventional arthroscopy) in the target knee planned for at least 12 months after first injection of the study drug
- Documented need for symptomatic PRN (as needed)-treatment for OA in the target knee with systemic non-steroidal anti-inflammatory drugs (NSAIDs) and/or other analgesics.
Key exclusion criteria (13 listed)
- any condition, including laboratory findings and findings in the medical history or in the pre-study assessments, that in the opinion of the Investigator constitutes a risk or contraindication for participation in the study or that could interfere with the study objectives, conduct or evaluation
- clinically significant abnormal hematology (hemoglobin, leucocytes, and platelets), or blood chemistry values (aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, and creatinine
- receipt of any investigational product or any experimental therapeutic procedure within the last 12 weeks preceding screening
- participation in FIH study 27575 or in a different cohort of this study
- i.a. treatment of the target knee with steroids or hyaluronic acid derivatives within the 3 months before baseline
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 |
|---|---|---|
| AS902330Also: rhFGF 18, Recombinant human fibroblast growth factor 18, Sprifermin10, 30 or 100 µg intra-articular injection per subject in the Single Ascending Dose (SAD) cohorts and 10, 30 or 100 µg intra-articular injection per week for three weeks per subject in the Multiple Ascending Dose (MAD) cohorts. | Biological | AS902330, Placebo |
Primary outcome
Change in cartilage thickness in the medial femoro-tibial compartment of the target knee joint, assessed by MRI
Time frame: 6 and 12 months after first injection
Nature, incidence and severity of local and systemic treatment-emergent adverse events (TEAEs)
Time frame: MAD Cohorts: 1 year + 1 month; SAD Cohorts: 4 Weeks
Proportion of subjects experiencing AIRs defined as increase of pain by 30mm on a 100mm visual analogue scale (VAS) associated with a self-reported synovial fluid effusion within 3 days following i.a. injection
Time frame: MAD Cohorts: Week 1, 2, 3, 13 14 and 15 (injections weeks); SAD Cohorts: Week 1
Laboratory assessments, including blood chemistry, hematology, urinalysis, and ECG
Time frame: MAD Cohorts: Week 0, 4, 13, 17, 52; SAD Cohorts: Weeks 0 & 4
10 secondary outcomes
Change in cartilage thickness in the medial femoro-tibial compartment of the target knee joint, assessed by MRI
Time frame: 52 Weeks
Change in total cartilage volume and thickness in the other compartments of the target knee joint, assessed by MRI
Time frame: 52 Weeks
Change over time of structural as well as compositional parameters of the knee joint (e.g. cartilage and bone), evaluated by MRI
Time frame: 52 Weeks
Change in WOMAC (Western Ontario MacMaster Osteoarthritis Questionaire) total score in the target knee from 5-point Likert scales
Time frame: 52 Weeks
Change in WOMAC Function and Pain index scores in the target knee
Time frame: 52 Weeks
Change in osteoarthritis (OA) pain in the target knee on a 100mm visual analogue scale (VAS)
Time frame: 52 Weeks
Change in JSW in the target knee by x-ray
Time frame: 52 Weeks
Presence of anti-AS902330 antibodies
Time frame: 52 Weeks
Blood levels of AS902330
Time frame: 52 Weeks
MRI at 3 months, score on WOMAC questionnaire at 3, 6 and 12 months.
Time frame: 6 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2014.
- Results publication: PubMed 24740822Lohmander LS, Hellot S, Dreher D, Krantz EF, Kruger DS, Guermazi A, Eckstein F. Intraarticular sprifermin (recombinant human fibroblast growth factor 18) in knee osteoarthritis: a randomized, double-blind, placebo-controlled trial. Arthritis Rheumatol. 2014 Jul;66(7):1820-31. doi: 10.1002/art.38614.
- Results publication: PubMed 24798571Onuora S. Osteoarthritis: Sprifermin shows cartilage-protective effects in knee OA. Nat Rev Rheumatol. 2014 Jun;10(6):322. doi: 10.1038/nrrheum.2014.68. Epub 2014 May 6. No abstract available.
- Derived from this study: PubMed 27393009Roemer FW, Aydemir A, Lohmander S, Crema MD, Marra MD, Muurahainen N, Felson DT, Eckstein F, Guermazi A. Structural effects of sprifermin in knee osteoarthritis: a post-hoc analysis on cartilage and non-cartilaginous tissue alterations in a randomized controlled trial. BMC Musculoskelet Disord. 2016 Jul 9;17:267. doi: 10.1186/s12891-016-1128-2.
- Derived from this study: PubMed 26138203Eckstein F, Wirth W, Guermazi A, Maschek S, Aydemir A. Brief report: intraarticular sprifermin not only increases cartilage thickness, but also reduces cartilage loss: location-independent post hoc analysis using magnetic resonance imaging. Arthritis Rheumatol. 2015 Nov;67(11):2916-22. doi: 10.1002/art.39265.
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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.
Donatus Dreher, MD, PhD study director
Merck Serono S.A., Geneva
28 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AS902330 in people with Knee Osteoarthritis, run by Merck KGaA, Darmstadt, Germany at 28 sites in 9 countries.
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 8 inclusion and 13 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: finished, as of the sponsor's last update on 25 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in Canada, Poland, Croatia, Finland, Serbia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in cartilage thickness in the medial femoro-tibial compartment of the target knee joint, assessed by MRI (time frame: 6 and 12 months after first injection). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01033994, which also lists 4 linked publications.
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 25 Jun 2014.