Rheumatoid ArthritisPhase 2BEGINNCT04004429
A Study of the Safety, Tolerability and Efficacy of Treatment With AP1189 in Early RA Patients With Active Joint Disease
A Phase 2 study testing 50 mg AP1189 and AP1189 in people with Rheumatoid Arthritis, run by SynAct Pharma Aps at 2 sites in 2 countries.
Trial summary
This is a multicenter, two-part, randomized, double-blind, placebo-kontrolled, 4-week study with repeated doses of AP1189. The study population will consist of newly diagnosed subjects with severe active Rheumatoid Arthritis, defined with a Clinical Disease Activity score (CDAI) > 22, who are to start up-titration… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- 50 mg AP1189 and AP1189
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 105 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 26 Aug 2019to 16 Nov 2021
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent has been obtained prior to initiating any study specific procedures
- Male and female subjects, 18 to 85 years of age
- Confirmed diagnosis of RA (Rheumatoid Arthritis) according to the 2010 American College of Rheumatology (ACR)/EULAR RA classification criteria
- Polyarthritis with joint swelling and tenderness of a minimum of three joints out of 68 joints tested
- Candidate for Methotrexate treatment
- Is about to begin treatment with MTX (Methotrexate)
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- Tested positive for anti-CCP (Anti-cyclic citrullinated peptide) or RF (Rheumatoid Factor)
- Severe active RA (Clinical Disease Activity Index (CDAI)) > 22) at screening and baseline
- Negative QFG-IT (QuantiFERON-in-Tube test)
- Subjects should be able to complete the PRO (Patient Reported Outcome) questionnaires
- Females of child-bearing potential may only participate if using reliable means of contraception or are post-menopausal. Surgically sterilized women at least 6 months prior to screening
- Females of childbearing potential must have a negative pregnancy test at screening and baseline
Who cannot join
- Participation in any other study involving investigational drug(s) within 4 weeks prior to study entry
- Major surgery within 8 weeks prior to screening or planned surgery within 1 month following randomization
- Rheumatic autoimmune disease other than RA, including SLE (systemic Lupus Erythematosus), MCTD (Mixed Connective Tissue Disease), scleroderma, polymyositis, or significant systemic involvement secondary to RA. Sjögren syndrome with RA is allowable
- Functional class IV as defined by the ACR Criteria for Classification of Functional Status in RA or wheelchair/bedbound
- Prior history of or current inflammatory joint disease other than RA
- Subjects with fibromyalgia
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- Initiation or change in dose for NSAIDs within 2 weeks prior to dosing with the IMP (Investigational Medicinal Product)
- Corticosteroids are prohibited within 2 weeks prior to screening (and during the entire treatment period and until the final visit
- Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine, or gastrointestinal disease
- Have prior renal transplant, current renal dialysis or severe renal insufficiency (determined by a derived glomerular filtration rate (GFR) using Cockcroft Gault Formula of ≤30 mL/min/1,73 m2 calculated by the local lab)
- Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids
- Evidence of active malignant disease
- Pregnant women or nursing mothers
- History of alcohol, drug, or chemical abuse within the 6 months prior to screening
- Neuropathies or other painful conditions that might interfere with pain evaluation
- Body weight of >150 kg
- Evidence of moderate and/or severe organ dysfunction
- Abnormal chest x-ray (as per the discretion of the investigator
- Evidence of positive hepatitis serology
- Evidence of peptic ulcer disease
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: A Double-blind, Multicenter, Two-part, Randomized, Placebo-controlled Study of the Safety, Tolerability, and Efficacy of 4 Weeks Treatment With AP1189 in Early Rheumatoid Arthritis (RA) Patients With Active Joint Disease
This is a multicenter, two-part, randomized, double-blind, placebo-kontrolled, 4-week study with repeated doses of AP1189. The study population will consist of newly diagnosed subjects with severe active Rheumatoid Arthritis, defined with a Clinical Disease Activity score (CDAI) > 22, who are to start up-titration with methotrexate.
Read the detailed description
A multicenter, two-part, randomized, double-blind, placebo-kontrolled, 4-week study with repeated doses of AP1189. The study population will consist of newly diagnosed subjects with severe active Rheumatoid Arthritis, defined with a Clinical Disease Activity score (CDAI) > 22, who are to start up-titration with methotrexate.
The study will be conducted in two parts separated by an interim analysis.
Part 1: The subjects will be randomized in a 1:1:1 ratio into: .
- AP1189 dose 50 mg
- AP1189 dose 100 mg
- placebo
INTERIM ANALYSIS
Part 2: All subjects will be randomized into either design 1, 2 or 3 based on data from the interim analysis.
- Design 1: AP1189 dose 50 mg or placebo in a 2:1 ratio
- Design 2: AP1189 dose 100 mg or placebo in a 2:1 ratio
- Design 3: Continue with the same doses as in Part 1
The purpose of this study is to determine the safety and efficacy of 2 doses of AP1189 compared with placebo after 4 weeks of treatment.
- Conditions
- Rheumatoid Arthritis
- Being tested
- 50 mg AP1189, AP1189, 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.
50 mg AP1189Drug
Also called AP1189
50 mg AP1189 powder in bottle
AP1189Drug
100 mg AP1189 powder in bottle
PlaceboDrug
Placebo powder in bottle
| Study group | Role | What they receive |
|---|---|---|
| 50 mg AP1189 | Experimental | 50 mg AP1189. The treatment is a 4 week treatment. Each daily dose will be administered as a suspension, i e. the powder will be added 50 ml water. Receives: Drug: 50 mg AP1189 |
| 100 mg AP1189 | Experimental | 100 mg AP1189. The treatment is a 4 week treatment. Each daily dose will be administered as a suspension, i e. the powder will be added 50 ml water. Receives: Drug: AP1189 |
| Placebo | Placebo comparator | Placebo. The treatment is a 4 week treatment. Each daily dose will be administered as a suspension i e. the powder will be added 50 ml water. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Clinical Disease Activity Index (CDAI)
The change in CDAI from severe (CDAI > 22) to moderate (CDAI <= 22) after 4 weeks treatment compared to baseline.
CDAI is calculated as a sum of:
- SJC (28): Number of Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees);
- TJC (28): Number of Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees)
- PGA: Patient Global Disease Activity (patient's self-assessment of overall RA disease activity on a scale 0-100, where 100 is maximal activity)
- IGA: Physician's Global Disease Activity (evaluator's assessment of the subject's overall RA disease activity on a scale 0-100, where 100 is maximal activity)
Measured: 4 weeks
Change in Clinical Disease Activity Index (CDAI)
The change in CDAI after 4 weeks treatment compared to baseline.
CDAI is calculated as a sum of:
- SJC (28): Number of Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees);
- TJC (28): Number of Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees)
- PGA: Patient Global Disease Activity (patient's self-assessment of overall RA disease activity on a scale 0-100, where 100 is maximal activity)
- IGA: Physician's Global Disease Activity (evaluator's assessment of the subject's overall RA disease activity on a scale 0-100, where 100 is maximal activity).
The CDAI score range is from 0 - 76, whereas a score of:
≤2.8 means Remission >2.8 and ≤10 means Low Disease Activity >10 and ≤22 means Moderate Disease Activity >22 means High Disease Activity
For the purpose of this study, a decrease in CDAI (improvement) is reported as - xx.xx).
Measured: 4 weeks
Secondary outcomes (3)
ACR (American College of Rheumatology) Response
Proportion of subjects achieving a response assessed by ACR20.
The ACR response rate ACR20 is defined as ≥20% improvement in swollen and tender joint counts (SJC/TJC) and 3 of the following 5 assessments: Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, Patient's Assessment of Pain, Health Assessment Questionnaire - Disability Index or C-Reactive Protein.
Proportion in the context of this protocol refers to number of participants.
Measured: 4 weeks
ACR (American College of Rheumatology) Response
Proportion of subjects achieving a response assessed by ACR50.
The ACR response rate ACR50 is defined as ≥50% improvement in swollen and tender joint counts (SJC/TJC) and 3 of the following 5 assessments: Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, Patient's Assessment of Pain, Health Assessment Questionnaire - Disability Index or C-Reactive Protein.
Proportion in the context of this protocol refers to number of participants.
Measured: 4 weeks
ACR (American College of Rheumatology) Response
Proportion of subjects achieving a response assessed by ACR70.
The ACR response rate ACR70 is defined as ≥70% improvement in swollen and tender joint counts (SJC/TJC) and 3 of the following 5 assessments: Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, Patient's Assessment of Pain, Health Assessment Questionnaire - Disability Index or C-Reactive Protein.
Proportion in the context of this protocol refers to number of participants.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2019
- Study start26 Aug 2019
- Primary completion16 Nov 2021
- Study completion16 Nov 2021
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.
- Other trials for Rheumatoid ArthritisStudies 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
- Model description
- Multicenter, two-part, randomized, double-blind, placebo-controlled 4-week study with repeated doses of AP1189
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- SynAct Pharma Aps
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ellen-Margrethe Hauge, Professor, Principal investigator, Aarhus University HospitalEspen A Haavardsholm, Concultant, PhD, Principal investigator, Diakonhjemmet Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04004429
- Sponsor's protocol ID
- SynAct-CS002
- Acronym
- BEGIN
- Status last verified
- Jul 2024
- First submitted
- 26 Jun 2019
- Last updated
- 10 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Multicenter, Two-part, Randomized, Placebo-controlled Study of the Safety, Tolerability, and Efficacy of 4 Weeks Treatment With AP1189 in Early Rheumatoid Arthritis (RA) Patients With Active Joint Disease
- ClinicalTrials.gov ID
- NCT04004429
- Acronym / sponsor ID
- BEGIN / SynAct-CS002
- Conditions
- Rheumatoid Arthritis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- SynAct Pharma ApsIndustry (pharma, biotech, devices)
- Study start
- 26 Aug 2019 (actual)
- Primary completion
- 16 Nov 2021 (actual)
- Study completion
- 16 Nov 2021 (actual)
- First posted
- 2 Jul 2019 (actual)
- Results
- Posted 10 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, two-part, randomized, double-blind, placebo-kontrolled, 4-week study with repeated doses of AP1189. The study population will consist of newly diagnosed subjects with severe active Rheumatoid Arthritis, defined with a Clinical Disease Activity score (CDAI) > 22, who are to start up-titration with methotrexate.
Detailed description
A multicenter, two-part, randomized, double-blind, placebo-kontrolled, 4-week study with repeated doses of AP1189. The study population will consist of newly diagnosed subjects with severe active Rheumatoid Arthritis, defined with a Clinical Disease Activity score (CDAI) > 22, who are to start up-titration with methotrexate.
The study will be conducted in two parts separated by an interim analysis.
Part 1: The subjects will be randomized in a 1:1:1 ratio into: .
- AP1189 dose 50 mg
- AP1189 dose 100 mg
- placebo
INTERIM ANALYSIS
Part 2: All subjects will be randomized into either design 1, 2 or 3 based on data from the interim analysis.
- Design 1: AP1189 dose 50 mg or placebo in a 2:1 ratio
- Design 2: AP1189 dose 100 mg or placebo in a 2:1 ratio
- Design 3: Continue with the same doses as in Part 1
The purpose of this study is to determine the safety and efficacy of 2 doses of AP1189 compared with placebo after 4 weeks of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Multicenter, two-part, randomized, double-blind, placebo-controlled 4-week study with repeated doses of AP1189
| Arm | Type | Receives |
|---|---|---|
| 50 mg AP1189 | Experimental | Drug: 50 mg AP118950 mg AP1189. The treatment is a 4 week treatment. Each daily dose will be administered as a suspension, i e. the powder will be added 50 ml water. |
| 100 mg AP1189 | Experimental | Drug: AP1189100 mg AP1189. The treatment is a 4 week treatment. Each daily dose will be administered as a suspension, i e. the powder will be added 50 ml water. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo. The treatment is a 4 week treatment. Each daily dose will be administered as a suspension i e. the powder will be added 50 ml water. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Written informed consent has been obtained prior to initiating any study specific procedures
- Male and female subjects, 18 to 85 years of age
- Confirmed diagnosis of RA (Rheumatoid Arthritis) according to the 2010 American College of Rheumatology (ACR)/EULAR RA classification criteria
- Polyarthritis with joint swelling and tenderness of a minimum of three joints out of 68 joints tested
- Candidate for Methotrexate treatment
Key exclusion criteria (20 listed)
- Participation in any other study involving investigational drug(s) within 4 weeks prior to study entry
- Major surgery within 8 weeks prior to screening or planned surgery within 1 month following randomization
- Rheumatic autoimmune disease other than RA, including SLE (systemic Lupus Erythematosus), MCTD (Mixed Connective Tissue Disease), scleroderma, polymyositis, or significant systemic involvement secondary to RA. Sjögren syndrome with RA is allowable
- Functional class IV as defined by the ACR Criteria for Classification of Functional Status in RA or wheelchair/bedbound
- Prior history of or current inflammatory joint disease other than RA
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 |
|---|---|---|
| 50 mg AP1189Also: AP118950 mg AP1189 powder in bottle | Drug | 50 mg AP1189 |
| AP1189100 mg AP1189 powder in bottle | Drug | 100 mg AP1189 |
| PlaceboPlacebo powder in bottle | Drug | Placebo |
Primary outcome
Change in Clinical Disease Activity Index (CDAI)
Time frame: 4 weeks
The change in CDAI from severe (CDAI > 22) to moderate (CDAI <= 22) after 4 weeks treatment compared to baseline. CDAI is calculated as a sum of: * SJC (28): Number of Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees); * TJC (28): Number of Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees) * PGA: Patient Global Disease Activity (patient's self-assessment of overall RA disease activity on a scale 0-100, where 100 is maximal activity) * IGA: Physician's Global Disease Activity (evaluator's assessment of the subject's overall RA disease activity on a scale 0-100, where 100 is maximal activity)
Change in Clinical Disease Activity Index (CDAI)
Time frame: 4 weeks
The change in CDAI after 4 weeks treatment compared to baseline. CDAI is calculated as a sum of: * SJC (28): Number of Swollen 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees); * TJC (28): Number of Tender 28-Joint Count (shoulders, elbows, wrists, MCPs, PIPs including thumb IP, knees) * PGA: Patient Global Disease Activity (patient's self-assessment of overall RA disease activity on a scale 0-100, where 100 is maximal activity) * IGA: Physician's Global Disease Activity (evaluator's assessment of the subject's overall RA disease activity on a scale 0-100, where 100 is maximal activity). The CDAI score range is from 0 - 76, whereas a score of: ≤2.8 means Remission >2.8 and ≤10 means Low Disease Activity >10 and ≤22 means Moderate Disease Activity >22 means High Disease Activity For the purpose of this study, a decrease in CDAI (improvement) is reported as - xx.xx).
3 secondary outcomes
ACR (American College of Rheumatology) Response
Time frame: 4 weeks
ACR (American College of Rheumatology) Response
Time frame: 4 weeks
ACR (American College of Rheumatology) Response
Time frame: 4 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
Ellen-Margrethe Hauge, Professor principal investigator
Aarhus University Hospital
Espen A Haavardsholm, Concultant, PhD principal investigator
Diakonhjemmet Hospital
2 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 50 mg AP1189 and AP1189 in people with Rheumatoid Arthritis, run by SynAct Pharma Aps at 2 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 12 inclusion and 20 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 10 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark, Norway. 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 10 Jul 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?
Change in Clinical Disease Activity Index (CDAI) (time frame: 4 weeks). 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 10 Jul 2024.