Knee OsteoarthritisPhase 1NCT00911469
Study of AS902330 (rhFGF-18) Administered Intra-articularly in Patients With Knee Primary Osteoarthritis Who Are Candidates for Total Knee Replacement
A Phase 1 study testing AS902330 in people with Knee Osteoarthritis, run by Merck KGaA, Darmstadt, Germany at 19 sites in 6 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
- 73 participants
- Where
- 19 sitesin 6 countries
- Study dates
- Nov 2007to Jun 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
- Established diagnosis of knee primary femoro-tibial OA by standard American College of Rheumatology Criteria (ACR) for at least six months (clinical AND radiological criteria)
- Postmenopausal or surgically sterile female ≥ 40 years of age Post-menopausal status will be confirmed by no menstrual periods for 12 consecutive months and no other biological or physiological cause for amenorrhea can be identified or Male ≥ 40 years of age willing to use contraception (condom with spermicide) from the first day of treatment until 2 months after the end of the treatment (3rd injection in Period 2) Even though systemic exposure of the drug is not foreseen at the doses used in this study, due to the absence of data on teratogenic potential of the drug, a very conservative approach on contraception is taken based on the spermatogenesis duration in humans.
- Candidate for Total Knee Replacement in the target knee, according to NIH consensus statement on Total Knee Replacement (2003)
- Date of planned Total Knee Replacement in the target knee ≥ 2 weeks after the anticipated last injection of study drug
- Subjects may be on treatment for symptomatic relief of OA, including NSAIDs (including Cox2 specific inhibitors); for NSAIDs, the dose should be stable for 4 weeks before baseline and during the study until day 4 after last injection. Paracetamol/acetaminophen (according to local standards and up to 4 grams per day) is allowed as rescue medication
- Willingness to stay in hospital for 24h after injection for SAD regimens and after first injection for MAD regimens (and up to 4 hours after second and third injections for MAD regimens) for safety and PK evaluation
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- Willingness to complete a diary card to evaluate local tolerability and adverse events throughout the study
- Subjects must have read and understood the informed consent form and must have signed it prior to any study related procedure
- Subjects must fully understand the requirements of the study and be willing to comply with all study visits and assessments
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 or biochemistry values (platelets, hemoglobin, leucocytes, alkaline phosphatase, AST, ALT, blood creatinine, bilirubin)
- Receipt of any investigational product or any experimental therapeutic procedure within the last 12 weeks preceding screening
- Intra-articular treatment with steroids or hyaluronic acid derivatives within the past 3 months (systemic symptomatic treatments with NSAIDs are allowed when stable for 4 weeks prior to first injection)
- Planned major surgery (e.g. joint replacement) within 2 weeks after last injection
- History of previous surgery (TKR or partial knee replacement) on the target knee
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- Lesions at the planned injection site that would present a contra-indication to local injection of the study drug (e.g., open wounds and infections of the skin)Any drug or nutraceutical treatment with potential DMOAD 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
- 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 history of other active malignancy within five years, except adequately treated basal cell and 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 Patients with risk factors for knee OA (e.g. obesity, meniscectomy) are not considered as having secondary OA and can be included in this study.
Trial locations and contacts
19 sites in 6 countries.
19 sites in 6 countries
Sweden6 sites
Sahlgrenska University Hospital/Östra
Gothenburg
Hässleholms Sjukhus
Hässleholm
Kungälv Sjukhus
Kungälv
Lund University Hospital
Lund
Malmö University Hospital
Malmö
Danderyds Sjukhus
Stockholm
Denmark5 sites
Frederiksberg Hospital
Frederiksberg
Gentofte Hospital
Hellerup
Nordsjællands Hospital - Hørsholm
Hørsholm
Silkeborg sygehus
Silkeborg
Regionshospitalet Viborg
Viborg
Finland3 sites
Kuopio University Hospital
Kuopio
Oulu University Hospital
Oulu
Turku University Central Hospital
Turku
South Africa3 sites
FARMOVS-PAREXEL (Pty) Ltd, University of the Free State
Bloemfontein
PAREXEL-George
George
PAREXEL-Port Elizabeth, Mercantile Hospital
Port Elizabeth
Bulgaria1 site
UMHAT "Sv. Ivan Rilski", Clinical Research Unit for Phase I
Sofia
About this study
Official title: A Randomised, Double-blind, Placebo-controlled, Multicentre, Single and Multiple Ascending Dose Study of AS902330 (rhFGF-18) Administered Intra-articularly in Patients With Knee Primary Osteoarthritis Who Are Candidates for Total Knee Replacement.
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 regeneration of the cartilage, and a narrowing of the space width between the knee joints in a selected region of the knee.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.
- Conditions
- Knee Osteoarthritis
- Being tested
- AS902330, Placebo
- Keywords
- Knee osteoarthritis, fibroblast growth factor 18
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AS902330Drug
3, 10, 30, 100 or 300 µg intra-articular injection per subject in the Single Ascending Dose (SAD) cohorts and 10, 30, 100, 300 µg or highest tolerated dose intra-articular injection per week for three weeks per subject in the Multiple Ascending Dose (MAD) cohorts.
PlaceboDrug
Placebo or, 3, 10, 30, 100 or 300 µg intra-articular injection per subject in SAD cohorts and placebo or, 10, 30, 100, 300 µg or highest tolerated dose of AS902330 intra-articular injection per week for three weeks per subject in MAD cohorts.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: AS902330 |
| 2 | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Nature, incidence and severity of treatment-emergent adverse events (TEAEs)
Measured: Up to 24 weeks post treatment
Proportion of subjects with predefined local AEs (acute inflammatory reactions defined as increase of pain by 30 mm - on a 100 mm VAS - associated with a self-reported synovial fluid effusion within 3 days following i.a. injection)
Measured: Up to 24 weeks post treatment
Local tolerability in the target knee
Measured: Up to 24 weeks post treatment
Laboratory safety parameters (including blood chemistry, haematology, and urinalysis) and ECG
Measured: Up to 24 weeks post treatment
Secondary outcomes (6)
Change over time in the levels of the following biomarkers: Biomarkers of anabolic effect on knee cartilage (markers of cartilage formation/synthesis)
Measured: Up to 24 weeks post treatment
Change over time in the levels of the following biomarkers: Biomarkers of catabolic effect on knee cartilage (markers of cartilage degradation)
Measured: Up to 24 weeks post treatment
Change over time in the levels of the following biomarkers: Biomarkers of Bone Metabolism
Measured: Up to 24 weeks post treatment
Change in levels of cytokines related to inflammation (IL1b, IL6, IL8, TNFα and IFNα)
Measured: Up to 24 weeks post treatment
Blood levels of AS902330
Measured: Up to 24 weeks post treatment
Presence of anti-AS902330 antibodies
Measured: Up to 24 weeks post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2009 (estimated)
- Study startNov 2007
- Primary completionApr 2010
- Study completionJun 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Serono S.A., Geneva
- Responsible party
- Sponsor
- Investigators
- Donatus Dreher, MD, PhD, Study director, Merck Serono SA - Geneva
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00911469
- Sponsor's protocol ID
- 27575
- Status last verified
- Aug 2014
- First submitted
- 29 May 2009
- Last updated
- 5 Aug 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, Double-blind, Placebo-controlled, Multicentre, Single and Multiple Ascending Dose Study of AS902330 (rhFGF-18) Administered Intra-articularly in Patients With Knee Primary Osteoarthritis Who Are Candidates for Total Knee Replacement.
- ClinicalTrials.gov ID
- NCT00911469
- Acronym / sponsor ID
- 27575
- Conditions
- Knee Osteoarthritis
- Keywords
- Knee osteoarthritis, fibroblast growth factor 18
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Collaborators
- Merck Serono S.A., Geneva
- Study start
- Nov 2007
- Primary completion
- Apr 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 2 Jun 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 regeneration of the cartilage, and a narrowing of the space width between the knee joints in a selected region of the knee.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.
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 |
|---|---|---|
| 1 | Experimental | Drug: AS902330 |
| 2 | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Established diagnosis of knee primary femoro-tibial OA by standard American College of Rheumatology Criteria (ACR) for at least six months (clinical AND radiological criteria)
- Postmenopausal or surgically sterile female ≥ 40 years of age Post-menopausal status will be confirmed by no menstrual periods for 12 consecutive months and no other biological or physiological cause for amenorrhea can be identified or Male ≥ 40 years of age willing to use contraception (condom with spermicide) from the first day of treatment until 2 months after the end of the treatment (3rd injection in Period 2) Even though systemic exposure of the drug is not foreseen at the doses used in this study, due to the absence of data on teratogenic potential of the drug, a very conservative approach on contraception is taken based on the spermatogenesis duration in humans.
- Candidate for Total Knee Replacement in the target knee, according to NIH consensus statement on Total Knee Replacement (2003)
- Date of planned Total Knee Replacement in the target knee ≥ 2 weeks after the anticipated last injection of study drug
- Subjects may be on treatment for symptomatic relief of OA, including NSAIDs (including Cox2 specific inhibitors); for NSAIDs, the dose should be stable for 4 weeks before baseline and during the study until day 4 after last injection. Paracetamol/acetaminophen (according to local standards and up to 4 grams per day) is allowed as rescue medication
Key exclusion criteria (12 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 or biochemistry values (platelets, hemoglobin, leucocytes, alkaline phosphatase, AST, ALT, blood creatinine, bilirubin)
- Receipt of any investigational product or any experimental therapeutic procedure within the last 12 weeks preceding screening
- Intra-articular treatment with steroids or hyaluronic acid derivatives within the past 3 months (systemic symptomatic treatments with NSAIDs are allowed when stable for 4 weeks prior to first injection)
- Planned major surgery (e.g. joint replacement) within 2 weeks after last injection
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 |
|---|---|---|
| AS9023303, 10, 30, 100 or 300 µg intra-articular injection per subject in the Single Ascending Dose (SAD) cohorts and 10, 30, 100, 300 µg or highest tolerated dose intra-articular injection per week for three weeks per subject in the Multiple Ascending Dose (MAD) cohorts. | Drug | 1 |
| PlaceboPlacebo or, 3, 10, 30, 100 or 300 µg intra-articular injection per subject in SAD cohorts and placebo or, 10, 30, 100, 300 µg or highest tolerated dose of AS902330 intra-articular injection per week for three weeks per subject in MAD cohorts. | Drug | 2 |
Primary outcome
Nature, incidence and severity of treatment-emergent adverse events (TEAEs)
Time frame: Up to 24 weeks post treatment
Proportion of subjects with predefined local AEs (acute inflammatory reactions defined as increase of pain by 30 mm - on a 100 mm VAS - associated with a self-reported synovial fluid effusion within 3 days following i.a. injection)
Time frame: Up to 24 weeks post treatment
Local tolerability in the target knee
Time frame: Up to 24 weeks post treatment
Laboratory safety parameters (including blood chemistry, haematology, and urinalysis) and ECG
Time frame: Up to 24 weeks post treatment
6 secondary outcomes
Change over time in the levels of the following biomarkers: Biomarkers of anabolic effect on knee cartilage (markers of cartilage formation/synthesis)
Time frame: Up to 24 weeks post treatment
Change over time in the levels of the following biomarkers: Biomarkers of catabolic effect on knee cartilage (markers of cartilage degradation)
Time frame: Up to 24 weeks post treatment
Change over time in the levels of the following biomarkers: Biomarkers of Bone Metabolism
Time frame: Up to 24 weeks post treatment
Change in levels of cytokines related to inflammation (IL1b, IL6, IL8, TNFα and IFNα)
Time frame: Up to 24 weeks post treatment
Blood levels of AS902330
Time frame: Up to 24 weeks post treatment
Presence of anti-AS902330 antibodies
Time frame: Up to 24 weeks post treatment
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 5 Aug 2014.
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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 SA - Geneva
19 sites in 6 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 19 sites in 6 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 9 inclusion and 12 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 5 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 19 sites in Sweden, Denmark, Finland, South Africa, Bulgaria and 1 more country. 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?
Nature, incidence and severity of treatment-emergent adverse events (TEAEs) (time frame: Up to 24 weeks post treatment). 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?
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 5 Aug 2014.