Dupuytren's DiseasePhase 2RIDDNCT03180957
Repurposing Anti-TNF for Treating Dupuytren's Disease
A Phase 2 study testing Adalimumab and Saline in people with Dupuytren's Disease, run by University of Oxford at 3 sites in 2 countries.
Trial summary
Dupuytren's disease is a very common condition, affecting 4% of the general UK and US population. It causes the fingers to curl irreversibly into the palm and can be extremely disabling. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Dupuytren's Disease
- What is being tested?
- Adalimumab and Saline
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 2 Mar 2016to Dec 2020
- 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
- Participant is willing and able to give informed consent for participation in the study.
- Male or Female, aged 18 years or above.
- For Part 1: Diagnosed with DD affecting the fingers resulting in flexion deformities of ≥30° at the metacarpophalangeal joint and or the proximal interphalangeal joint with impaired hand function and awaiting surgery. Or for Part 2: Participants with early disease nodules who have shown or reported progression of the disease in the previous 6 months with flexion deformities of their fingers of ≤30° at the metacarpophalangeal and/or at the proximal interphalangeal joint, i.e. total flexion deformity of up to 60°.
- The DD nodule to be treated must be distinct and identifiable.
- Female participants of child bearing potential, and male participants whose partner is of child bearing potential, must be willing to ensure that they or their partner use effective contraception throughout the treatment period and for 5 months following the last research injection. Acceptable methods of contraception include: a combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods), injectables, the combined oral contraceptive pill (at a stable dose for at least 3 months before entering the study), an intrauterine device, vasectomised partner, or true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant).
- Participant results from safety screening tests within normal ranges within 12 weeks of enrolment, with the exception that an earlier clear chest x-ray result may be used where this is in accordance with the time frames of local standard procedures for anti-TNF screening.
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- Able (in the Investigators opinion) and willing to comply with all study requirements.
- Willing to allow his or her general practitioner to be notified of participation in the study.
- Sufficient language fluency to ensure informed consent is obtained and to complete the questionnaires pertaining to hand function.
Who cannot join
- For Part 1: Participant has previously had fasciectomy, dermofasciectomy, needle fasciotomy, collagenase injection, steroid injection or radiotherapy to treat Dupuytren's disease in the digit concerned. Or for Part 2: Participant has previously had fasciectomy, dermofasciectomy, needle fasciotomy, collagenase injection, steroid injection to the digit to be treated or radiotherapy to treat Dupuytren's disease in the hand concerned.
- Female participant who is pregnant, lactating or planning pregnancy during the course of the study and for 5 months following last injection.
- Male participant who is planning a pregnancy during the course of the study and for 5 months following last injection.
- Significant renal or hepatic impairment.
- For Part 1: Scheduled elective surgery or other procedures requiring general anaesthesia during the study other than the scheduled Dupuytren's surgery. Or for Part 2: Scheduled elective surgery or other procedures requiring general anaesthesia during the study
- Participant who has ever been diagnosed with cancer, is terminally ill or is inappropriate for placebo medication
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- Systemic inflammatory disorder such as rheumatoid arthritis (RA) or inflammatory bowel disease.
- Any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.
- Participated in another research study involving an investigational medicinal product in the past 12 weeks.
- Known allergy to any anti-TNF agent.
- Have HIV or hepatitis B or C.
- Known to have an infection or history of repeated infections.
- History of Tuberculosis (TB).
- Have Multiple Sclerosis (MS) or other demyelinating disease.
- History of local injection site reactions.
- Needle phobia.
- Have moderate or severe heart failure.
- Part 1: Being treated with coumarin anticoagulants, such as warfarin.
- Have known lung fibrosis (thickening of lung tissue).
- Being treated with concomitant biologic DMARDS.
- Have received a live vaccine within the previous 4 weeks. Participants may receive concurrent vaccinations but must avoid the use of live vaccines for 12 weeks after their last injection.
- Part1: Have received parenteral steroid within the previous 6 weeks.
- Part 2: Participants at risk of Hepatitis B infection.
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
United Kingdom2 sites
NHS Lothian
Edinburgh, EH1 3EG
Oxford University Hospitals NHS Foundation Trust
Oxford, OX3 9DU
About this study
Official title: A Multi-centre, Double Blind, Randomised, Placebo-controlled, Parallel Group, Phase II Trial to Determine the Efficacy of Intra-nodular Injection of Anti-TNF to Control Disease Progression in Early Dupuytren's Disease, With a Dose Response.
Dupuytren's disease is a very common condition, affecting 4% of the general UK and US population. It causes the fingers to curl irreversibly into the palm and can be extremely disabling. The disease usually starts as a small firm lump (nodule) in the palm, and in about 40% of patients advances to form cords that pull the fingers into the palm. There is no approved treatment for the early stage of disease. Once patients have established deformities, the diseased tissue can removed by surgery or cut using less invasive techniques such as a needle or an enzyme. However, recovery following surgery usually takes several months and recurrence rates with the less invasive techniques are high.
The investigators have unravelled the cellular process that initiates and maintains the disease progress and identified tumour necrosis factor (TNF) as a new target for treatment. Based on these findings the investigators plan to test the effects of adalimumab, an anti-TNF drug which currently approved for use in patients with rheumatoid arthritis and other inflammatory conditions. The aim of the study is to find out whether treatment by injection with adalimumab directly into the diseased tissue will control the advance of early Dupuytren's disease better than a placebo injection with normal saline.
Read more
The investigators will first carry out a small trial in up to 40 patients with established disease to determine the best dose that reduces the activity of the cells responsible for the disorder (Dose Response study). In this part patients who will be having surgery to remove their diseased tissue will receive a single injection of adalimumab into the nodule in their hand about 2 weeks before surgery. The tissue that is then removed during surgery will be analysed in the investigator's laboratories to determine the effect of the drug on the tissue. Patients will be followed for 12 weeks after surgery.
In the second part of the study the investigators will assess whether the optimal dose of the drug prevents early disease advancing in 138 patients (Early Disease study). Patients who take part in the second part of the study will receive a total of 4 injections of adalimumab into the nodule in their hand at three monthly intervals. They will then be checked at 3 \& 9 months after the last injection. In additional to assessing the effect of the injections on the nodule and hand function, information will also be collected to assess the cost effectiveness of the treatment.
- Conditions
- Dupuytren's Disease
- Being tested
- Adalimumab, Saline
- Keywords
- Dupuytren, adalimumab, anti TNF, phase II clinical trial, randomized controlled trial, double-blind method, Dupuytren's, Dupuytren's contracture
- Medical subject headings
- Dupuytren Contracture
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdalimumabDrug
Also called Humira
SalineDrug
| Study group | Role | What they receive |
|---|---|---|
| Anti-TNF | Experimental | adalimumab Receives: Drug: Adalimumab |
| Placebo | Placebo comparator | saline Receives: Drug: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Early Disease: Nodule Hardness at 12 Months
Tonometry - A hardness score in arbitrary units with 0 being the lowest hardness and 100 being the greatest hardness units on a scale.
Measured: 12 months
Secondary outcomes (4)
Early Disease: Nodule Size
Measured in mm^2 where 0 is the smallest and 50 is the largest unit on a scale
Measured: 12 months
Early Disease: Grip Strength
Jamar meter
Measured: 12 months
Early Disease: Extension Deficit of Affected Joint
Overall passive extension deficit of joint affected by treated nodule (degrees)
Measured: 12 months
Early Disease: Patient Reported Outcomes
Michigan Hand Questionnaire - overall hand function with 0 as the lowest ability and 100 best possible ability units on a scale.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2017
- Study start2 Mar 2016
- Primary completionNov 2020
- Study completionDec 2020
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 (3)Papers the sponsor has linked to this study.
- Other trials for Dupuytren's DiseaseStudies of the same condition, open and under way.
- More trials run by University of OxfordThe 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
- 140 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Department of Health, United Kingdom, Wellcome Trust, 180 Therapeutics LP
- Responsible party
- Sponsor
- Investigators
- Jagdeep Nanchahal, PhD FRCS, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03180957
- Sponsor's protocol ID
- 11069
- Other IDs
- HICF-R8-433, 2015-001780-40, ISRCTN27786905, 15/SC/0259, CTU0028, 2015
- Acronym
- RIDD
- Status last verified
- May 2022
- First submitted
- 23 May 2017
- Last updated
- 28 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Nanchahal J, Ball C, Davidson D, Williams L, Sones W, McCann FE, Cabrita M, Swettenham J, Cahoon NJ, Copsey B, Anne Francis E, Taylor PC, Black J, Barber VS, Dutton S, Feldmann M, Lamb SE. Anti-Tumour Necrosis Factor Therapy for Dupuytren's Disease: A Randomised Dose Response Proof of Concept Phase 2a Clinical Trial. EBioMedicine. 2018 Jul;33:282-288. doi: 10.1016/j.ebiom.2018.06.022. Epub 2018 Jul 6.
PubMed 29983350Nanchahal J, Ball C, Rombach I, Williams L, Kenealy N, Dakin H, O'Connor H, Davidson D, Werker P, Dutton SJ, Feldmann M, Lamb SE. Anti-tumour necrosis factor therapy for early-stage Dupuytren's disease (RIDD): a phase 2b, randomised, double-blind, placebo-controlled trial. Lancet Rheumatol. 2022 Jun;4(6):E407-E416. doi: 10.1016/S2665-9913(22)00093-5. Epub 2022 Apr 29.
PubMed 35949922Dakin H, Rombach I, Dritsaki M, Gray A, Ball C, Lamb SE, Nanchahal J. Cost-effectiveness of adalimumab for early-stage Dupuytren's disease : an economic evaluation based on a randomized controlled trial and individual-patient simulation model. Bone Jt Open. 2022 Nov;3(11):898-906. doi: 10.1302/2633-1462.311.BJO-2022-0103.R2.
PubMed 36378072
Study at a glance
From the registry record, last updated by the sponsor on 28 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-centre, Double Blind, Randomised, Placebo-controlled, Parallel Group, Phase II Trial to Determine the Efficacy of Intra-nodular Injection of Anti-TNF to Control Disease Progression in Early Dupuytren's Disease, With a Dose Response.
- ClinicalTrials.gov ID
- NCT03180957
- Acronym / sponsor ID
- RIDD / 11069
- Conditions
- Dupuytren's Disease
- Keywords
- Dupuytren, adalimumab, anti TNF, phase II clinical trial, randomized controlled trial, double-blind method, Dupuytren's, Dupuytren's contracture
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 140 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Department of Health, United Kingdom, Wellcome Trust, 180 Therapeutics LP
- Study start
- 2 Mar 2016 (actual)
- Primary completion
- Nov 2020 (actual)
- Study completion
- Dec 2020 (actual)
- First posted
- 8 Jun 2017 (actual)
- Results
- Posted 28 Jun 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Dupuytren's disease is a very common condition, affecting 4% of the general UK and US population. It causes the fingers to curl irreversibly into the palm and can be extremely disabling. The disease usually starts as a small firm lump (nodule) in the palm, and in about 40% of patients advances to form cords that pull the fingers into the palm. There is no approved treatment for the early stage of disease. Once patients have established deformities, the diseased tissue can removed by surgery or cut using less invasive techniques such as a needle or an enzyme. However, recovery following surgery usually takes several months and recurrence rates with the less invasive techniques are high.
The investigators have unravelled the cellular process that initiates and maintains the disease progress and identified tumour necrosis factor (TNF) as a new target for treatment. Based on these findings the investigators plan to test the effects of adalimumab, an anti-TNF drug which currently approved for use in patients with rheumatoid arthritis and other inflammatory conditions. The aim of the study is to find out whether treatment by injection with adalimumab directly into the diseased tissue will control the advance of early Dupuytren's disease better than a placebo injection with normal saline.
The investigators will first carry out a small trial in up to 40 patients with established disease to determine the best dose that reduces the activity of the cells responsible for the disorder (Dose Response study). In this part patients who will be having surgery to remove their diseased tissue will receive a single injection of adalimumab into the nodule in their hand about 2 weeks before surgery. The tissue that is then removed during surgery will be analysed in the investigator's laboratories to determine the effect of the drug on the tissue. Patients will be followed for 12 weeks after surgery.
In the second part of the study the investigators will assess whether the optimal dose of the drug prevents early disease advancing in 138 patients (Early Disease study). Patients who take part in the second part of the study will receive a total of 4 injections of adalimumab into the nodule in their hand at three monthly intervals. They will then be checked at 3 \& 9 months after the last injection. In additional to assessing the effect of the injections on the nodule and hand function, information will also be collected to assess the cost effectiveness of the treatment.
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 |
|---|---|---|
| Anti-TNF | Experimental | Drug: Adalimumabadalimumab |
| Placebo | Placebo comparator | Drug: Salinesaline |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Participant is willing and able to give informed consent for participation in the study.
- Male or Female, aged 18 years or above.
- For Part 1: Diagnosed with DD affecting the fingers resulting in flexion deformities of ≥30° at the metacarpophalangeal joint and or the proximal interphalangeal joint with impaired hand function and awaiting surgery. Or for Part 2: Participants with early disease nodules who have shown or reported progression of the disease in the previous 6 months with flexion deformities of their fingers of ≤30° at the metacarpophalangeal and/or at the proximal interphalangeal joint, i.e. total flexion deformity of up to 60°.
- The DD nodule to be treated must be distinct and identifiable.
- Female participants of child bearing potential, and male participants whose partner is of child bearing potential, must be willing to ensure that they or their partner use effective contraception throughout the treatment period and for 5 months following the last research injection. Acceptable methods of contraception include: a combination of male condom with either cap, diaphragm or sponge with spermicide (double barrier methods), injectables, the combined oral contraceptive pill (at a stable dose for at least 3 months before entering the study), an intrauterine device, vasectomised partner, or true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant).
Key exclusion criteria (23 listed)
- For Part 1: Participant has previously had fasciectomy, dermofasciectomy, needle fasciotomy, collagenase injection, steroid injection or radiotherapy to treat Dupuytren's disease in the digit concerned. Or for Part 2: Participant has previously had fasciectomy, dermofasciectomy, needle fasciotomy, collagenase injection, steroid injection to the digit to be treated or radiotherapy to treat Dupuytren's disease in the hand concerned.
- Female participant who is pregnant, lactating or planning pregnancy during the course of the study and for 5 months following last injection.
- Male participant who is planning a pregnancy during the course of the study and for 5 months following last injection.
- Significant renal or hepatic impairment.
- For Part 1: Scheduled elective surgery or other procedures requiring general anaesthesia during the study other than the scheduled Dupuytren's surgery. Or for Part 2: Scheduled elective surgery or other procedures requiring general anaesthesia during the study
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 |
|---|---|---|
| AdalimumabAlso: Humira | Drug | Anti-TNF |
| Saline | Drug | Placebo |
Primary outcome
Early Disease: Nodule Hardness at 12 Months
Time frame: 12 months
Tonometry - A hardness score in arbitrary units with 0 being the lowest hardness and 100 being the greatest hardness units on a scale.
4 secondary outcomes
Early Disease: Nodule Size
Time frame: 12 months
Early Disease: Grip Strength
Time frame: 12 months
Early Disease: Extension Deficit of Affected Joint
Time frame: 12 months
Early Disease: Patient Reported Outcomes
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 29983350Nanchahal J, Ball C, Davidson D, Williams L, Sones W, McCann FE, Cabrita M, Swettenham J, Cahoon NJ, Copsey B, Anne Francis E, Taylor PC, Black J, Barber VS, Dutton S, Feldmann M, Lamb SE. Anti-Tumour Necrosis Factor Therapy for Dupuytren's Disease: A Randomised Dose Response Proof of Concept Phase 2a Clinical Trial. EBioMedicine. 2018 Jul;33:282-288. doi: 10.1016/j.ebiom.2018.06.022. Epub 2018 Jul 6.
- Results publication: PubMed 35949922Nanchahal J, Ball C, Rombach I, Williams L, Kenealy N, Dakin H, O'Connor H, Davidson D, Werker P, Dutton SJ, Feldmann M, Lamb SE. Anti-tumour necrosis factor therapy for early-stage Dupuytren's disease (RIDD): a phase 2b, randomised, double-blind, placebo-controlled trial. Lancet Rheumatol. 2022 Jun;4(6):E407-E416. doi: 10.1016/S2665-9913(22)00093-5. Epub 2022 Apr 29.
- Results publication: PubMed 36378072Dakin H, Rombach I, Dritsaki M, Gray A, Ball C, Lamb SE, Nanchahal J. Cost-effectiveness of adalimumab for early-stage Dupuytren's disease : an economic evaluation based on a randomized controlled trial and individual-patient simulation model. Bone Jt Open. 2022 Nov;3(11):898-906. doi: 10.1302/2633-1462.311.BJO-2022-0103.R2.
- 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.
Jagdeep Nanchahal, PhD FRCS principal investigator
University of Oxford
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Adalimumab and Saline in people with Dupuytren's Disease, run by University of Oxford at 3 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 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 28 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United Kingdom, Netherlands. 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 28 Jun 2024). 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?
Early Disease: Nodule Hardness at 12 Months (time frame: 12 months). 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 NCT03180957, which also lists 3 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 28 Jun 2024.