Ankylosing SpondylitisPhase 2STARTNCT00944658
Spondylitis Trial of Apremilast for Better Rheumatic Therapy
A Phase 2 study testing Apremilast in people with Ankylosing Spondylitis, run by Imperial College London at 1 site in United Kingdom.
Trial summary
This study will evaluate the effectiveness of apremilast in AS as measured by improvement in patients' signs and symptoms of the disease and changes in imaging. Additionally the safety and tolerability of apremilast in AS will be assessed. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ankylosing Spondylitis
- What is being tested?
- Apremilast
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 2009to Jan 2011
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent to participate in this trial
- Diagnosis of ankylosing spondylitis as defined by the modified New York criteria (1984) as follows:
- a history of inflammatory back pain;
- limitation of motion of the lumbar spine in both the sagittal and frontal planes;
- limited chest expansion, relative to standard values for age and sex;
- definite radiographic / imaging evidence of sacroiliitis and/or spinal inflammation
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- Patients must have daily spinal pain and stiffness for at least 2 weeks prior to randomization. This is defined by having a score of >1 on questions #2 and #5 of the BASDAI score for the 2 weeks prior to randomization.
- Patients receiving NSAIDS and/or COX-2 inhibitors must be on stable doses for at least 2 weeks prior to randomization.
- Age >18 years
- Male and female patients, who are not surgically sterile or postmenopausal, must use reliable methods of birth control for the duration of the study. Males must agree to use barrier contraception for 3 months following the end of the trial.
- Women of childbearing potential, not surgically sterile or postmenopausal, must have a negative serum beta HCG.
Who cannot join
- Use of DMARDs (methotrexate, d-penicillamine, sulfasalazine, azathioprine, hydroxychloroquine, or gold) within 8 weeks of randomization.
- Use of systemic corticosteroids within 4 weeks of randomization
- Use of intravenous or intra-articular corticosteroids within 4 weeks of randomization
- Use of TNF alpha blockers (eg, infliximab, adalimumab) or etanercept as follows:
- Compound PK Exclusion period Etanercept T ½ = 102 hrs = 4.25 days 4 weeks Adalimumab T ½ 2 wks; 5 half lives 10 weeks 10 weeks Infliximab T ½ 7.7-9.5 d 12 weeks 8 weeks after maintenance dose median infx conc 0.5-6 mcg/ml
- Therapy with an investigational agent within 30 days of randomization or 5 half-lives (pharmacokinetic or pharmacodynamic), which ever is longer
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- Known HIV or hepatitis B or C infection
- History of active Mycobacterium tuberculosis infection (any subspecies) within 3 years prior to the screening visit. Infections that occurred > 3 years prior to entry must have been effectively treated.
- History of incompletely treated latent Mycobacterium tuberculosis infection (as indicated by a positive Purified Protein Derivative [PPD] skin test)
- Clinically significant abnormality on chest x-ray (CXR) if mantoux >5mm or ELISPOT positive
- History of other rheumatic autoimmune diseases (eg, systemic lupus erythematosus, rheumatoid arthritis, etc.)
- Pregnant or nursing women
- Any condition, in the investigator's opinion, which places the patient at an undue risk by participating in the study.
- Contraindication to MRI and other MRI exclusions following local centre guidelines (Appendix H)
- An estimated glomerular filtration rate (eGFR) of < 60 ml/min (because of the small risk of nephrogenic sclerosing fibrosis with gadolinium intravenous contrast), if patient is to have MRI with gadolinium contrast .
- Claustrophobia
- Hemoglobin < 9 g/dL
- White blood cell (WBC) count < 3000 /μL (≥ 3.0 X 109/L) and ≥ 14,000/μL (≥ 20 X 109/L)
- Neutrophils < 1500 /μL (< 1.5 X 109/L)
- Platelets < 100,000 /μL (< 100 X 109/L)
- Serum creatinine > 1.5 mg/dL (> 132.6 μmol/L)
- Total bilirubin > 2.0 mg/dL
- Aspartate transaminase (AST [serum glutamic oxaloacetic transaminase, SGOT]) and alanine transaminase (ALT [serum glutamate pyruvic transaminase, SGPT]) > 1.5x upper limit of normal (ULN)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
The Kennedy Institute Clinical Trials Unit, 4 West, Charing Cross Hospital
London, W6 8RF
About this study
Official title: Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004)in the Treatment of Ankylosing Spondylitis (AS)
This study will evaluate the effectiveness of apremilast in AS as measured by improvement in patients' signs and symptoms of the disease and changes in imaging. Additionally the safety and tolerability of apremilast in AS will be assessed.
Read the detailed description
Presently, there are very few treatments available which affect the progression of the disease in the spine. The only proven treatment is the use of drugs inhibiting tumour necrosis factor alpha (TNF). However, there are limitations with this treatment in that it needs to be administered via an injection and is also very expensive. Therefore it is necessary to develop new therapeutic agents for this condition.
Apremilast (the study drug) is an oral tablet which has been shown to inhibit TNF production in a mouse model of inflammation. It has also been used in clinical trials for asthma and psoriasis in humans with good affect and tolerability.
These studies were funded by Celgene Corporation and they will be funding this study.
The patients will be recruited from hospitals by Consultant referral. The patients will have had AS for at least 2 years and their symptoms will have been uncontrolled on conventional non-steroidal anti-inflammatory drugs such as ibuprofen. Patients will be randomised to either receive apremilast or a placebo and treated over a period of 12 weeks. They will then be followed up for 28 days after the treatment period.
- Conditions
- Ankylosing Spondylitis
- Being tested
- Apremilast, Placebo (sugar pill)
- Keywords
- Ankylosing spondylitis, Imaging
- Medical subject headings
- Spondylitis, Ankylosing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApremilastDrug
10mg twice a day, dose was titrated by 20mg every 2 days until the maximum dose 30mg twice a day for 12weeks
Placebo (sugar pill)Drug
twice a day
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | placebo twice a day for 12 weeks, 4 weeks follow up Receives: Drug: Placebo (sugar pill) |
| Apremilast | Active comparator | 30 mg twice a day for 12 weeks, 4 weeks follow up Receives: Drug: Apremilast |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes of Apremilast in Patients With AS, Changes in BASDAI Score From Baseline
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), 0 - 10 score, higher reduction in the scores suggest better suboptimal control of disease.
Measured: Baseline and 12 weeks
Changes of Apremilast on the Signs and Symptoms of AS, Night Pain From Baseline
This endpoint the night time pain score change was recorded by questionnaire to evaluate the Apremilast effect on symptom, higher reduction better improvement.
scale is 0-10
Measured: Baseline and 12 weeks
Effect of Apremilast in Patients With AS, Changes in BASFI Score
Bath Ankylosing Spondylitis Functional Index (BASFI), 0 - 10 score, higher reduction in the scores suggest better suboptimal control of disease.
Measured: Baseline and 12 weeks
Secondary outcomes (1)
The Safety and Tolerability of Apremilast in AS, Number of Participants With Adverse Events
To evaluate the safety and tolerability of Apremilast in AS, the investigator recorded the incidence of adverse events.
Measured: 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2009 (estimated)
- Study startAug 2009
- Primary completionJan 2011
- Study completionJan 2011
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ankylosing SpondylitisStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- 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
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation
- Responsible party
- Sponsor
- Investigators
- Peter Taylor, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00944658
- Sponsor's protocol ID
- 112008
- Other IDs
- 2008-004229-40, 2008
- Acronym
- START
- Status last verified
- Nov 2019
- First submitted
- 20 Jul 2009
- Last updated
- 6 Dec 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pathan E, Abraham S, Van Rossen E, Withrington R, Keat A, Charles PJ, Paterson E, Chowdhury M, McClinton C, Taylor PC. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in ankylosing spondylitis. Ann Rheum Dis. 2013 Sep 1;72(9):1475-80. doi: 10.1136/annrheumdis-2012-201915. Epub 2012 Sep 14.
PubMed 22984171
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-blind, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of Apremilast (CC-10004)in the Treatment of Ankylosing Spondylitis (AS)
- ClinicalTrials.gov ID
- NCT00944658
- Acronym / sponsor ID
- START / 112008
- Conditions
- Ankylosing Spondylitis
- Keywords
- Ankylosing spondylitis, Imaging
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Celgene Corporation
- Study start
- Aug 2009 (actual)
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 23 Jul 2009 (estimated)
- Results
- Posted 6 Dec 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the effectiveness of apremilast in AS as measured by improvement in patients' signs and symptoms of the disease and changes in imaging. Additionally the safety and tolerability of apremilast in AS will be assessed.
Detailed description
Presently, there are very few treatments available which affect the progression of the disease in the spine. The only proven treatment is the use of drugs inhibiting tumour necrosis factor alpha (TNF). However, there are limitations with this treatment in that it needs to be administered via an injection and is also very expensive. Therefore it is necessary to develop new therapeutic agents for this condition.
Apremilast (the study drug) is an oral tablet which has been shown to inhibit TNF production in a mouse model of inflammation. It has also been used in clinical trials for asthma and psoriasis in humans with good affect and tolerability.
These studies were funded by Celgene Corporation and they will be funding this study.
The patients will be recruited from hospitals by Consultant referral. The patients will have had AS for at least 2 years and their symptoms will have been uncontrolled on conventional non-steroidal anti-inflammatory drugs such as ibuprofen. Patients will be randomised to either receive apremilast or a placebo and treated over a period of 12 weeks. They will then be followed up for 28 days after the treatment period.
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 |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo (sugar pill)placebo twice a day for 12 weeks, 4 weeks follow up |
| Apremilast | Active comparator | Drug: Apremilast30 mg twice a day for 12 weeks, 4 weeks follow up |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Written informed consent to participate in this trial
- Diagnosis of ankylosing spondylitis as defined by the modified New York criteria (1984) as follows:
- Patients must have daily spinal pain and stiffness for at least 2 weeks prior to randomization. This is defined by having a score of >1 on questions #2 and #5 of the BASDAI score for the 2 weeks prior to randomization.
- Patients receiving NSAIDS and/or COX-2 inhibitors must be on stable doses for at least 2 weeks prior to randomization.
- Age >18 years
Key exclusion criteria (23 listed)
- Use of DMARDs (methotrexate, d-penicillamine, sulfasalazine, azathioprine, hydroxychloroquine, or gold) within 8 weeks of randomization.
- Use of systemic corticosteroids within 4 weeks of randomization
- Use of intravenous or intra-articular corticosteroids within 4 weeks of randomization
- Use of TNF alpha blockers (eg, infliximab, adalimumab) or etanercept as follows:
- Compound PK Exclusion period Etanercept T ½ = 102 hrs = 4.25 days 4 weeks Adalimumab T ½ 2 wks; 5 half lives 10 weeks 10 weeks Infliximab T ½ 7.7-9.5 d 12 weeks 8 weeks after maintenance dose median infx conc 0.5-6 mcg/ml
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 |
|---|---|---|
| Apremilast10mg twice a day, dose was titrated by 20mg every 2 days until the maximum dose 30mg twice a day for 12weeks | Drug | Apremilast |
| Placebo (sugar pill)twice a day | Drug | Placebo |
Primary outcome
Changes of Apremilast in Patients With AS, Changes in BASDAI Score From Baseline
Time frame: Baseline and 12 weeks
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), 0 - 10 score, higher reduction in the scores suggest better suboptimal control of disease.
Changes of Apremilast on the Signs and Symptoms of AS, Night Pain From Baseline
Time frame: Baseline and 12 weeks
This endpoint the night time pain score change was recorded by questionnaire to evaluate the Apremilast effect on symptom, higher reduction better improvement. scale is 0-10
Effect of Apremilast in Patients With AS, Changes in BASFI Score
Time frame: Baseline and 12 weeks
Bath Ankylosing Spondylitis Functional Index (BASFI), 0 - 10 score, higher reduction in the scores suggest better suboptimal control of disease.
1 secondary outcome
The Safety and Tolerability of Apremilast in AS, Number of Participants With Adverse Events
Time frame: 16 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 22984171Pathan E, Abraham S, Van Rossen E, Withrington R, Keat A, Charles PJ, Paterson E, Chowdhury M, McClinton C, Taylor PC. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in ankylosing spondylitis. Ann Rheum Dis. 2013 Sep 1;72(9):1475-80. doi: 10.1136/annrheumdis-2012-201915. Epub 2012 Sep 14.
- Individual participant dataSharing planned: No
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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.
Peter Taylor principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Apremilast in people with Ankylosing Spondylitis, run by Imperial College London at 1 site in United Kingdom.
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 11 inclusion and 23 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 6 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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 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 6 Dec 2019). 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?
Changes of Apremilast in Patients With AS, Changes in BASDAI Score From Baseline (time frame: Baseline and 12 weeks). The study lists 3 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 NCT00944658, which also lists 1 linked publication.
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 6 Dec 2019.