A Study of the Safety, Tolerability and Efficacy of Treat... | NCT04004429

NCT04004429

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	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.	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.	Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
50 mg AP1189	Drug	50 mg AP1189 powder in bottle	50 mg AP1189	AP1189

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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)	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).	4 weeks

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

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)
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

Exclusion Criteria:

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
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

Exclusion criteria that only applies for Norway

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

Name	Affiliation	Role
Ellen-Margrethe Hauge, Professor	Aarhus University Hospital	Principal Investigator
Espen A Haavardsholm, Concultant, PhD	Diakonhjemmet Hospital	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Aarhus Universitetshospital		Aarhus		8200	Denmark
Diakonhjemmet Sykehus

Arm/Group Information

ID	Title	Description
FG000	50 mg AP1189	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. 50 mg AP1189: 50 mg AP1189 powder in bottle
FG001	100 mg AP1189	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. AP1189: 100 mg AP1189 powder in bottle
FG002	Placebo	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. Placebo: Placebo powder in bottle

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	50 mg AP1189	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. 50 mg AP1189: 50 mg AP1189 powder in bottle
BG001	100 mg AP1189

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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)

The number of participants analyzed differs from the overall number of participants. Participants that received rescue medication during the treatment period was excluded from the analyses.

Posted

Count of Participants

Participants

4 weeks

ID	Title	Description
OG000	50 mg AP1189

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	50 mg AP1189	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. 50 mg AP1189: 50 mg AP1189 powder in bottle

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 14, 2021	Sep 28, 2022	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Nov 22, 2021	Sep 28, 2022	SAP_001.pdf

ID	Term
D001168	Arthritis
D007592	Joint Diseases
D009140	Musculoskeletal Diseases
D012216	Rheumatic Diseases