Rheumatoid Arthritis, DMARD-naive and Early Disease PatientsPhase 2NCT03163966
A Study of the EP4 Antagonist CR6086 in Combination With Methotrexate, in DMARD-naïve Patients With Early Rheumatoid Arthritis
A Phase 2 study testing CR6086 and Methotrexate in people with Rheumatoid Arthritis, DMARD-naive and Early Disease Patients, run by Rottapharm Biotech at 1 site in Czechia.
Trial summary
CR6086 is a new, potent and selective, orally available, small molecule prostaglandin EP4 receptor antagonist, endowed with immunomodulatory properties. The pharmacological properties of CR6086, along with its oral bioavailability, predictable pharmacokinetics and good safety, make it the ideal candidate to be tested… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rheumatoid Arthritis, DMARD-naive and Early Disease Patients
- What is being tested?
- CR6086 and Methotrexate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 248 participants
- Where
- 1 siteCzechia
- Study dates
- 5 Oct 2017to 8 Jan 2019
- Phase
- Phase 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female aged ≥18 years.
- Patients with diagnosis of definite Rheumatoid Arthritis (RA) according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria.
- Disease duration no longer than 1 year (early RA).
- Patients must be naïve to any DMARDs (csDMARDs, or bDMARDs, or tsDMARDs) other than hydroxychloroquine.
- Patients with "moderate" disease activity as documented by a Disease Activity Score 28 (DAS28) (C-Reactive Protein - CRP) index score > 3.2.
- Patients with serum C-Reactive Protein (hsCRP) higher than the upper limit of normal.
- Patients positive for serum rheumatoid factor (RF) or anti-cyclic citrullinated peptide antibodies (ACPA).
Who cannot join
- Rheumatic autoimmune disease other than RA, or current inflammatory joint disease other than RA, or non-inflammatory type of musculoskeletal condition (e.g., osteoarthritis or fibromyalgia) that in the Investigator's opinion is symptomatic and/or severe enough to interfere with the study procedures.
- History of gastric/duodenal ulcers and gastrointestinal bleeding, or gastrointestinal diseases known to interfere with the absorption or excretion of medications.
- Severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease.
- Malignancy (with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ) active during the 12 months preceding the Screening Visit.
- Acute hepatitis (during the 3 months preceding the Screening Visit), chronic hepatitis, or HIV infection.
- History of alcohol or drug abuse, or
Show all 17Show fewer
- allergy/sensitivity to lactose.
- Vaccination with live vaccines during the 6 weeks preceding the Screening Visit.
- Clinically significant abnormalities in haematology, serum alkaline-phosphatase, gamma-glutamyl-transferase, alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine clearance, 12-lead ECG.
- Use of hydroxychloroquine during the 4 weeks preceding the Screening Visit.
- Treatment with oral corticosteroids, unless maintained at doses equivalent to ≤10 mg/day prednisone ≥7 days before the Screening Visit.
- Use of nonsteroidal anti-inflammatory drugs (NSAIDs).
- Use of other investigational drugs/treatments, or enrolment in a clinical trial during the 6 months preceding the Screening Visit.
- For women of childbearing potential:
- Pregnancy (i.e. positive pregnancy test at Screening) or breastfeeding
- Failure to agree to practice a highly effective method of contraception.
- For sexually active men with a female partner of childbearing potential: failure to agree to use contraception.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double Blind, Placebo-controlled, Dose Response, Phase II, Multicentre Trial to Evaluate the Efficacy, Safety and Pharmacokinetics of Oral CR6086 Administered at the Doses of 30, 90 or 180 mg Bid for 12 Weeks in Combination With Methotrexate, in DMARD-naïve Patients With Early Rheumatoid Arthritis
CR6086 is a new, potent and selective, orally available, small molecule prostaglandin EP4 receptor antagonist, endowed with immunomodulatory properties. The pharmacological properties of CR6086, along with its oral bioavailability, predictable pharmacokinetics and good safety, make it the ideal candidate to be tested alone or in combination with methotrexate (MTX) in patients with early Rheumatoid Arthritis who are naïve to Disease-Modifying Antirheumatic Drugs (DMARDs). The compound has indeed the potential to provide a safer and more effective treatment than MTX (or other conventional synthetic DMARDs - csDMARDs), and could significantly improve the proportion of responder patients and avoid/delay the recourse to biological DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs).
Read the detailed description
There is growing evidence that EP4 receptors play an important role in the altered immune response observed in autoimmune diseases. These findings point to the EP4 receptor as a rational target for the development of novel Disease-Modifying Antirheumatic Drugs (DMARDs)/immunomodulators which, in addition, have direct anti-inflammatory properties. The potential for CR6086 to act as a DMARD was extensively demonstrated in a series of widely accepted models of arthritis in rodents, where oral CR6086 was effective in all the parameters examined, including oedema, clinical arthritis score, and histology. CR6086 performed much better than nonsteroidal anti-inflammatory drugs (NSAIDs, that lack the immunomodulatory properties of an EP4 receptor antagonist and are scarcely effective), better than first-line csDMARDs such as MTX, and similarly to immunosuppressive bDMARDs such as TNF-blockers, or tsDMARDs such as JAK inhibitors.
In the present study, CR6086 (or placebo) will be administered in a dose-response fashion for 12 weeks to DMARD-naïve patients with early Rheumatoid Arthritis, in combination with oral MTX. The treatment duration and study design will allow to test the effects of the new treatment on clinical outcomes of disease activity, laboratory biomarkers and imaging parameters.
- Being tested
- CR6086, Methotrexate, Placebo
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CR6086Drug
oral CR6086 capsules
MethotrexateDrug
oral Methotrexate tablets
PlaceboDrug
oral CR6086 Placebo capsules
| Study group | Role | What they receive |
|---|---|---|
| CR6086 30 mg | Experimental | CR6086 30 mg bid for 12 weeks as add-on to methotrexate (MTX) once weekly. MTX uptitrated to stable dosing as per standard guidelines Receives: Drug: CR6086; Drug: Methotrexate |
| CR6086 90 mg | Experimental | CR6086 90 mg bid for 12 weeks as add-on to MTX once weekly. MTX uptitrated to stable dosing as per standard guidelines Receives: Drug: CR6086; Drug: Methotrexate |
| CR6086 180 mg | Experimental | CR6086 180 mg bid for 12 weeks as add-on to MTX once weekly. MTX uptitrated to stable dosing as per standard guidelines Receives: Drug: CR6086; Drug: Methotrexate |
| Placebo | Experimental | CR6086 matching placebo bid for 12 weeks as add-on to MTX once weekly. MTX uptitrated to stable dosing as per standard guidelines Receives: Drug: Methotrexate; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
American College of Rheumatology 20% improvement (ACR20) responder rate
Measured: 12 weeks
Secondary outcomes (11)
ACR50 responder rate
Measured: 12 weeks
ACR70 responder rate
Measured: 12 weeks
Disease Activity Score on 28-joint count (DAS28)
Measured: 12 weeks
Clinical Disease Activity Index (CDAI)
Measured: 12 weeks
Simplified Disease Activity Index (SDAI)
Measured: 12 weeks
ACR/EULAR remission criteria
Measured: 12 weeks
Adverse Events
number of patients with Adverse Events
Measured: 12 weeks
Routine Laboratory determinations
Measured: 12 weeks
Pharmacokinetics (PK) of Methotrexate and CR6086 in combination
Main PK endpoint: AUCinf (ng.h/mL). Area under the plasma concentration vs time curve extrapolated to infinity
Measured: 12 weeks
Biochemical markers
Serum biomarkers of disease activity
Measured: 12 weeks
Imaging biomarkers
Dynamic Contrast-Enhanced MRI (DCE-MRI)
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2017
- Study start5 Oct 2017
- Primary completion8 Jan 2019
- Study completion8 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid Arthritis, DMARD-naive and Early Disease PatientsStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 248 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rottapharm Biotech
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03163966
- Sponsor's protocol ID
- CR6086-2-02
- Status last verified
- Dec 2017
- First submitted
- 8 May 2017
- Last updated
- 5 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double Blind, Placebo-controlled, Dose Response, Phase II, Multicentre Trial to Evaluate the Efficacy, Safety and Pharmacokinetics of Oral CR6086 Administered at the Doses of 30, 90 or 180 mg Bid for 12 Weeks in Combination With Methotrexate, in DMARD-naïve Patients With Early Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT03163966
- Acronym / sponsor ID
- CR6086-2-02
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 248 participants (actual)
- Lead sponsor
- Rottapharm BiotechIndustry (pharma, biotech, devices)
- Study start
- 5 Oct 2017 (actual)
- Primary completion
- 8 Jan 2019 (actual)
- Study completion
- 8 Jan 2019 (actual)
- First posted
- 23 May 2017 (actual)
- 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.
CR6086 is a new, potent and selective, orally available, small molecule prostaglandin EP4 receptor antagonist, endowed with immunomodulatory properties. The pharmacological properties of CR6086, along with its oral bioavailability, predictable pharmacokinetics and good safety, make it the ideal candidate to be tested alone or in combination with methotrexate (MTX) in patients with early Rheumatoid Arthritis who are naïve to Disease-Modifying Antirheumatic Drugs (DMARDs). The compound has indeed the potential to provide a safer and more effective treatment than MTX (or other conventional synthetic DMARDs - csDMARDs), and could significantly improve the proportion of responder patients and avoid/delay the recourse to biological DMARDs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs).
Detailed description
There is growing evidence that EP4 receptors play an important role in the altered immune response observed in autoimmune diseases. These findings point to the EP4 receptor as a rational target for the development of novel Disease-Modifying Antirheumatic Drugs (DMARDs)/immunomodulators which, in addition, have direct anti-inflammatory properties. The potential for CR6086 to act as a DMARD was extensively demonstrated in a series of widely accepted models of arthritis in rodents, where oral CR6086 was effective in all the parameters examined, including oedema, clinical arthritis score, and histology. CR6086 performed much better than nonsteroidal anti-inflammatory drugs (NSAIDs, that lack the immunomodulatory properties of an EP4 receptor antagonist and are scarcely effective), better than first-line csDMARDs such as MTX, and similarly to immunosuppressive bDMARDs such as TNF-blockers, or tsDMARDs such as JAK inhibitors.
In the present study, CR6086 (or placebo) will be administered in a dose-response fashion for 12 weeks to DMARD-naïve patients with early Rheumatoid Arthritis, in combination with oral MTX. The treatment duration and study design will allow to test the effects of the new treatment on clinical outcomes of disease activity, laboratory biomarkers and imaging parameters.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| CR6086 30 mg | Experimental | Drug: CR6086, Drug: MethotrexateCR6086 30 mg bid for 12 weeks as add-on to methotrexate (MTX) once weekly. MTX uptitrated to stable dosing as per standard guidelines |
| CR6086 90 mg | Experimental | Drug: CR6086, Drug: MethotrexateCR6086 90 mg bid for 12 weeks as add-on to MTX once weekly. MTX uptitrated to stable dosing as per standard guidelines |
| CR6086 180 mg | Experimental | Drug: CR6086, Drug: MethotrexateCR6086 180 mg bid for 12 weeks as add-on to MTX once weekly. MTX uptitrated to stable dosing as per standard guidelines |
| Placebo | Experimental | Drug: Methotrexate, Drug: PlaceboCR6086 matching placebo bid for 12 weeks as add-on to MTX once weekly. MTX uptitrated to stable dosing as per standard guidelines |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female aged ≥18 years.
- Patients with diagnosis of definite Rheumatoid Arthritis (RA) according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria.
- Disease duration no longer than 1 year (early RA).
- Patients must be naïve to any DMARDs (csDMARDs, or bDMARDs, or tsDMARDs) other than hydroxychloroquine.
- Patients with "moderate" disease activity as documented by a Disease Activity Score 28 (DAS28) (C-Reactive Protein - CRP) index score > 3.2.
Key exclusion criteria (17 listed)
- Rheumatic autoimmune disease other than RA, or current inflammatory joint disease other than RA, or non-inflammatory type of musculoskeletal condition (e.g., osteoarthritis or fibromyalgia) that in the Investigator's opinion is symptomatic and/or severe enough to interfere with the study procedures.
- History of gastric/duodenal ulcers and gastrointestinal bleeding, or gastrointestinal diseases known to interfere with the absorption or excretion of medications.
- Severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, metabolic, endocrine, pulmonary, cardiac or neurologic disease.
- Malignancy (with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ) active during the 12 months preceding the Screening Visit.
- Acute hepatitis (during the 3 months preceding the Screening Visit), chronic hepatitis, or HIV infection.
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 |
|---|---|---|
| CR6086oral CR6086 capsules | Drug | CR6086 180 mg, CR6086 30 mg, CR6086 90 mg |
| Methotrexateoral Methotrexate tablets | Drug | CR6086 180 mg, CR6086 30 mg, CR6086 90 mg, Placebo |
| Placebooral CR6086 Placebo capsules | Drug | Placebo |
Primary outcome
American College of Rheumatology 20% improvement (ACR20) responder rate
Time frame: 12 weeks
11 secondary outcomes
ACR50 responder rate
Time frame: 12 weeks
ACR70 responder rate
Time frame: 12 weeks
Disease Activity Score on 28-joint count (DAS28)
Time frame: 12 weeks
Clinical Disease Activity Index (CDAI)
Time frame: 12 weeks
Simplified Disease Activity Index (SDAI)
Time frame: 12 weeks
ACR/EULAR remission criteria
Time frame: 12 weeks
Adverse Events
Time frame: 12 weeks
Routine Laboratory determinations
Time frame: 12 weeks
Pharmacokinetics (PK) of Methotrexate and CR6086 in combination
Time frame: 12 weeks
Biochemical markers
Time frame: 12 weeks
Imaging biomarkers
Time frame: 12 weeks
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 Oct 2021.
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.
The record lists no contact. Use the official record to reach the sponsor.
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 CR6086 and Methotrexate in people with Rheumatoid Arthritis, DMARD-naive and Early Disease Patients, run by Rottapharm Biotech at 1 site in Czechia.
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 7 inclusion and 17 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 Oct 2021. 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 Czechia. 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. 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?
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?
American College of Rheumatology 20% improvement (ACR20) responder rate (time frame: 12 weeks). 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 Oct 2021.