OsteoarthritisPhase 1/2NCT00819572
Study of Intra-articular DLX105 Applied to Patients With Severely Painful Osteoarthritis of the Knee
A Phase 1/2 study testing DLX105, a single-chain (scFv) antibody fragment against TNF-alpha in people with Osteoarthritis, run by ESBATech AG at 10 sites in 2 countries.
Trial summary
The purpose of this study is to determine whether an intra-articular injection of DLX105 to the knee joint of patients suffering from severly painful osteoarthritis is safe and reduces pain. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Osteoarthritis
- What is being tested?
- DLX105, a single-chain (scFv) antibody fragment against TNF-alpha
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 10 sitesin 2 countries
- Study dates
- Dec 2008to Sep 2010
- Phase
- Phase 1/2
- 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
- Body mass index < 30.
- Patients with diagnosed OA of the knee (unilateral or bilateral) according to the American College of Rheumatology (ACR) Criteria for classification of idiopathic OA (clinical and radiological criteria) of the knee at Screening (for ACR criteria, see Appendix 16.1).
- Radiographic evidence of tibiofemoral OA within the last 6 months before Screening, consisting of Grade II or Grade III changes, according to Kellgren-Lawrence grading system.
- Presence of pain in the index knee (in case of bilateral OA, "index knee" is the more painful knee) defined by a level of ≥ 60 mm on a 100 mm (linear) VAS at Screening.
- Paracetamol and NSAIDs (apart from acetyl salicylic acid ≤ 100 mg/day) must be withdrawn at least 24 hours prior to Screening .
- Doses of "chondroprotective" agents containing glucosamine and/or chondroitin sulphate must be stable for at least 3 months prior to Screening.
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- Doses of any non-prescription medication claiming effects on signs or symptoms of OA must be stable for at least 3 months prior to Screening.
- Use of non-pharmacological treatment modalities must be stable for at least 3 months prior to Screening.
- Negative QuantiFERON-TB Gold test.
Who cannot join
- Radiographic evidence of tibiofemoral OA within the last 6 months before Screening, consisting of Grade IV, according to Kellgren-Lawrence grading system.
- Instability of the index knee joint of > 10° as assessed by goniometer at Screening.
- Arthroscopic or open surgery to the index knee joint within 6 months prior to Screening.
- Post-traumatic or any other secondary OA of the knee.
- Isolated OA of the patello-femoral joint.
- Co-morbidity that would confound measurement of knee pain
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- Evidence of any inflammatory arthritis.
- History of Reiter's Syndrome, RA, psoriatic arthritis, ankylosing spondylitis, lymphoma, arthritis associated with inflammatory bowel disease, sarcoidosis, amyloidosis, or any other inflammatory disease (immune mediated inflammatory disease) that may affect the knee.
- Local or systemic contraindication for an i.a. injection at Screening or Baseline.
- Any i.a. injection (corticosteroids, hyaluronic acid, etc.) within the 3 months prior to Screening.
- History of high risk exposure to Mycobacterium tuberculosis.
- Human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection.
- Uncontrolled diabetes or cardiovascular disease (New York Heart Association criteria III + IV), including uncontrolled hypertension (> 160/100 mmHg).
- Active infectious episodes, or history of recurrent or chronic systemic infections.
- Malignancy within 5 years prior to Screening, except for surgically-cured non melanoma skin cancer or cervical carcinoma in situ.
- Significant haematological disease within 1 month prior to Screening.
- Moderately to severely impaired hepatic function, or laboratory values reflecting inadequate hepatic function
- Additional criteria for the sub-population of patients undergoing MRI:
- Contraindications to MRI.
- Known allergy to gadolinium contrast material.
- Presence of chronic renal failure defined by a calculated creatinine clearance (CrCl) of < 60 mL/min, using the Cockcroft-Gault estimate for GFR
Trial locations and contacts
10 sites in 2 countries.
10 sites in 2 countries
Switzerland6 sites
Rheumaklinik Kantonsspital Aarau
Aarau, 5000
Rheumatologische Universitäts-Poliklinik, Felix-Platter Spital Basel
Basel, 4055
Service de rhumatologie, Centre Hospitalier Universitaire, Lausanne
Lausanne, 1005
Kantonsspital St.Gallen, Rheumatologie
Sankt Gallen, 9007
Zentrum für Rheuma und Knochenerkrankungen
Zurich, 8038
Universitätsspital Zürich, Rheumaklinik
Zurich, 8091
Germany4 sites
Prof. Dr. med. Georg Schett
Erlangen, 91054
Dr. René Martz
Hamburg, 22143
Dr. Sven Ostermeier
Hanover, 30625
Prof. Dr. Manfred Hartard
Munich, 80809
About this study
Official title: A Double-blind, Randomised, Placebo-controlled Phase I/IIa Study to Investigate the Safety, Tolerability and Efficacy on Pain of Intra-articular DLX105 Applied to Patients With Severely Painful Osteoarthritis of the Knee
The purpose of this study is to determine whether an intra-articular injection of DLX105 to the knee joint of patients suffering from severly painful osteoarthritis is safe and reduces pain.
Read the detailed description
Treatment options for patients suffering from osteoarthritis remain limited. TNF-alpha has been identified as a major pro-inflammatory component inducing and perpetuating peripheral hyperalgesia and cartilage degeneration in various preclinical studies. DLX105 is an antibody fragment of comparably low molecular weight, associated with an exceptional local biodistribution pattern upon intra-articular injection. In addition, due to its short systemic half life as compared to conventional monoclonal antibodies, systemic exposure to DLX105 upon intra-articular administration is low. This study is designed to determine the safety and local tolerability profile of single intra-articular injections of ESBA105 as well as to define DLX105's effect size and effect duration in reducing pain of patients suffering from severely painful osteoarthritis of the knee. The study will be conducted in two sequential parts. In a first part, 4 different doses of DLX105 will be compared in a sequential, escalating scheme against placebo treatment in a total of 24 patients. In the second part of the study, two doses of DLX105 chosen based on safety data from the first part will be compared to placebo treatment in a total of 102 patients.
- Conditions
- Osteoarthritis
- Being tested
- DLX105, a single-chain (scFv) antibody fragment against TNF-alpha, Placebo
- Keywords
- Osteoarthritis, TNF-alpha, DLX105, scFv antibody fragment, pain, fragment, antibody fragment
- Medical subject headings
- Osteoarthritis, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DLX105, a single-chain (scFv) antibody fragment against TNF-alphaBiological
Comparison of two different doses of intra-articular DLX105
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | DLX105 low dose Receives: Biological: DLX105, a single-chain (scFv) antibody fragment against TNF-alpha |
| 2 | Experimental | DLX105 high dose Receives: Biological: DLX105, a single-chain (scFv) antibody fragment against TNF-alpha |
| 3 | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from Baseline (Day 0) to Day 7 in a 100mm Visual Analogue Scale (VAS) to assess the intensity of knee pain.
Measured: Day 7 after intra-articular injection
Safety assessment during the study period. Safety endpoints will include the nature and incidence of AEs, physical examination findings, changes in vital signs, and laboratory test results.
Measured: 8 weeks / 12 weeks
Secondary outcomes (1)
Change from baseline in Western Ontario and McMaster Universities Osteoarthritis (WOMAC™) scoring
Measured: Day 7 after intra-articular injection
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2009 (estimated)
- Study startDec 2008
- Primary completionSep 2010
- Study completionSep 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- ESBATech AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Prof. Georg Schett, MD, Study chair, University Hospital of Erlangen, GermanyProf. Hansjörg Häuselmann, MD, Principal investigator, Rheumazentrum, Zurich Switzerland (Country Coordinator)PD.Dr. Diego Kyburz, MD, Principal investigator, University Hospital Zurich, Switzerland (Country Coordinator)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00819572
- Sponsor's protocol ID
- DLX105CRD02
- Status last verified
- Sep 2010
- First submitted
- 8 Jan 2009
- Last updated
- 24 Sep 2010
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomised, Placebo-controlled Phase I/IIa Study to Investigate the Safety, Tolerability and Efficacy on Pain of Intra-articular DLX105 Applied to Patients With Severely Painful Osteoarthritis of the Knee
- ClinicalTrials.gov ID
- NCT00819572
- Acronym / sponsor ID
- DLX105CRD02
- Conditions
- Osteoarthritis
- Keywords
- Osteoarthritis, TNF-alpha, DLX105, scFv antibody fragment, pain, fragment, antibody fragment
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- ESBATech AGIndustry (pharma, biotech, devices)
- Study start
- Dec 2008
- Primary completion
- Sep 2010 (actual)
- Study completion
- Sep 2010 (actual)
- First posted
- 9 Jan 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.
The purpose of this study is to determine whether an intra-articular injection of DLX105 to the knee joint of patients suffering from severly painful osteoarthritis is safe and reduces pain.
Detailed description
Treatment options for patients suffering from osteoarthritis remain limited. TNF-alpha has been identified as a major pro-inflammatory component inducing and perpetuating peripheral hyperalgesia and cartilage degeneration in various preclinical studies. DLX105 is an antibody fragment of comparably low molecular weight, associated with an exceptional local biodistribution pattern upon intra-articular injection. In addition, due to its short systemic half life as compared to conventional monoclonal antibodies, systemic exposure to DLX105 upon intra-articular administration is low. This study is designed to determine the safety and local tolerability profile of single intra-articular injections of ESBA105 as well as to define DLX105's effect size and effect duration in reducing pain of patients suffering from severely painful osteoarthritis of the knee. The study will be conducted in two sequential parts. In a first part, 4 different doses of DLX105 will be compared in a sequential, escalating scheme against placebo treatment in a total of 24 patients. In the second part of the study, two doses of DLX105 chosen based on safety data from the first part will be compared to placebo treatment in a total of 102 patients.
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 |
|---|---|---|
| 1 | Experimental | Biological: DLX105, a single-chain (scFv) antibody fragment against TNF-alphaDLX105 low dose |
| 2 | Experimental | Biological: DLX105, a single-chain (scFv) antibody fragment against TNF-alphaDLX105 high dose |
| 3 | 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)
- Body mass index < 30.
- Patients with diagnosed OA of the knee (unilateral or bilateral) according to the American College of Rheumatology (ACR) Criteria for classification of idiopathic OA (clinical and radiological criteria) of the knee at Screening (for ACR criteria, see Appendix 16.1).
- Radiographic evidence of tibiofemoral OA within the last 6 months before Screening, consisting of Grade II or Grade III changes, according to Kellgren-Lawrence grading system.
- Presence of pain in the index knee (in case of bilateral OA, "index knee" is the more painful knee) defined by a level of ≥ 60 mm on a 100 mm (linear) VAS at Screening.
- Paracetamol and NSAIDs (apart from acetyl salicylic acid ≤ 100 mg/day) must be withdrawn at least 24 hours prior to Screening .
Key exclusion criteria (21 listed)
- Radiographic evidence of tibiofemoral OA within the last 6 months before Screening, consisting of Grade IV, according to Kellgren-Lawrence grading system.
- Instability of the index knee joint of > 10° as assessed by goniometer at Screening.
- Arthroscopic or open surgery to the index knee joint within 6 months prior to Screening.
- Post-traumatic or any other secondary OA of the knee.
- Isolated OA of the patello-femoral joint.
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 |
|---|---|---|
| DLX105, a single-chain (scFv) antibody fragment against TNF-alphaComparison of two different doses of intra-articular DLX105 | Biological | 1, 2 |
| Placebo | Drug | 3 |
Primary outcome
Change from Baseline (Day 0) to Day 7 in a 100mm Visual Analogue Scale (VAS) to assess the intensity of knee pain.
Time frame: Day 7 after intra-articular injection
Safety assessment during the study period. Safety endpoints will include the nature and incidence of AEs, physical examination findings, changes in vital signs, and laboratory test results.
Time frame: 8 weeks / 12 weeks
1 secondary outcome
Change from baseline in Western Ontario and McMaster Universities Osteoarthritis (WOMAC™) scoring
Time frame: Day 7 after intra-articular injection
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 24 Sep 2010.
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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.
Prof. Georg Schett, MD study chair
University Hospital of Erlangen, Germany
Prof. Hansjörg Häuselmann, MD principal investigator
Rheumazentrum, Zurich Switzerland (Country Coordinator)
PD.Dr. Diego Kyburz, MD principal investigator
University Hospital Zurich, Switzerland (Country Coordinator)
10 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing DLX105, a single-chain (scFv) antibody fragment against TNF-alpha in people with Osteoarthritis, run by ESBATech AG at 10 sites in 2 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 21 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 24 Sep 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Switzerland, Germany. 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 combined 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.
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?
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 from Baseline (Day 0) to Day 7 in a 100mm Visual Analogue Scale (VAS) to assess the intensity of knee pain. (time frame: Day 7 after intra-articular injection). The study lists 2 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 24 Sep 2010.