A two-part, randomized, double-blind, multi-center, placebo-controlled study of the dose-range, safety and efficacy of 4 and 12 weeks of treatment with AP1189 in adult rheumatoid arthritis (RA) patients with an inadequate response to Methotrexate (MTX) alone - RESOLVE
- Conditions
- Rheumatoid ArthritisMedDRA version: 23.1Level: LLTClassification code 10003268Term: Arthritis rheumatoidSystem Organ Class: 100000004859Therapeutic area: Diseases [C] - Immune System Diseases [C20]
- Registration Number
- EUCTR2022-002605-26-BG
- Lead Sponsor
- SynAct Pharma ApS
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 420
Inclusion criteria are the same for the Part A and the Part B population:
1. Written informed consent has been obtained prior to initiating any study specific
procedures
2. Male and female subjects, 18 to 85 years of age
3. Confirmed diagnosis of RA according to the 2010 ACR/EULAR RA classification
criteria and ACR class I-III
a. = 6 swollen joints (based on 66 joint counts) and = 6 tender joints (based on
68 joint counts)
b. Must meet at least one of the following parameters at Screening:
i. A positive result for anti-CCP or RF,
OR
ii. Serum CRP = 6 mg/L based on central laboratory value
4. Ongoing methotrexate therapy =12 weeks in a stable dose of 7.5 to 25 mg/week for
at least 4 weeks prior to the baseline visit
5. Subject has an inadequate clinical response to maximally tolerated methotrexate
therapy
6. Subjects should be receiving an adequate and prescribed stable dose of folic acid
(=5 mg/week total dose or as per local clinical practice) which should be confirmed
or initiated at screening and continued throughout the study
7. Negative QuantiFERON-in-Tube test (QFG-IT) (Mantoux test can be used if QFGIT
is not possible)
8. Subjects should be able to complete (read and write) the Patient-Reported Outcome
questionnaires (PRO questionnaires)
9. Females of childbearing potential must have a negative pregnancy test at screening and again at baseline
10. Sexually active females of childbearing potential and male participants are excluded
if not practicing two different methods of birth control with their partner during the
study and for at least 90 days after the last dose of study drug or who will not
remain abstinent during the study and for 90 days after the last dose. If employing
birth control, each couple must use two of the following precautions: vasectomy,
tubal ligation, vaginal diaphragm, intrauterine device, birth control pill, birth
control implant, birth control depot injections, condom with spermicide, or sponge
with spermicide.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 280
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 140
Exclusion criteria are the same for the Part A and the Part B populations:
1. Use of all other biologic or nonbiologic DMARDs and immunosuppressive therapy
within 4 weeks or five half-lives (whichever is longer) prior to administration of the
first dose of study drug
2. Oral steroids at a dose >10 mg/day of prednisone (or equivalent) or a prescription
for oral steroids which has changed within 4 weeks of baseline
3. Receipt of an intra-articular or parenteral corticosteroid injection within 4 weeks
prior to baseline
4. Participation in any other study involving investigational drug(s) within 4 weeks
prior to baseline
5. Major surgery (including joint operation) within 8 weeks prior to screening or
planned surgery within the period of the study participation
6. Rheumatic autoimmune disease other than RA, including systemic lupus
erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma,
polymyositis, or significant systemic involvement secondary to RA (e.g., vasculitis,
pulmonary fibrosis or Felty’s syndrome). Sjögren’s syndrome with RA is allowable
7. Functional class IV as defined by the ACR Criteria for Classification of Functional
Status in RA or wheelchair/bedbound
8. Prior history of or current inflammatory joint disease other than RA (e.g., gout,
reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme
disease)
9. Subjects with fibromyalgia
10. Initiation or change in dose for NSAIDs (including low-dose aspirin and COX-2
inhibitors) within 2 weeks prior to baseline
11. Evidence of serious uncontrolled concomitant cardiovascular (including clinically
significantly prolonged QTc interval), nervous system, pulmonary (including
obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled
diabetes mellitus), or gastrointestinal disease
12. Serum Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)
higher than 1.5 x the upper limit of normal (ULN) and alkaline phosphatase (ALP)
and/or bilirubin values above the ULN at the screening visit.
13. Prior renal transplant, current renal dialysis, or moderate to severe renal
insufficiency (determined by a derived glomerular filtration rate (GFR) using
Cockcroft Gault formula of =60 ml/min/1,73m²)
14. Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel
disease where flares are commonly treated with oral or parenteral corticosteroids
15. Evidence of active malignant disease (except basal cell carcinoma of the skin that
has been excised and cured)
16. Pregnant women or nursing (breastfeeding) mothers
17. History of alcohol, drug, or chemical abuse within the 6 months prior to screening
18. Neuropathy or other painful, chronic conditions that might interfere with pain
evaluation
19. Body weight of >150 kg
20. HBsAg positive and/or Anti-HBc with sign of current infection. Participants with
positive Anti-HBc should be tested for IgM anti-HBc - if IgM anti-HBc is positive
the patient will be excluded.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method