A Study of the Safety, Tolerability and Efficacy of Treatment With AP1189 in Early RA Patients With Active Joint Disease

NCT04004429 | Completed Phase 2 Results DMC

• 1 other identifier: SynAct-CS002
• Study Type: interventional
• Target: 105
• Locations: 2 countries
• Sites: 2

Brief 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 with methotrexate.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (2)

• 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 (3)

• ACR (American College of Rheumatology) Response

  4 weeks

• ACR (American College of Rheumatology) Response

  4 weeks

• ACR (American College of Rheumatology) Response

  4 weeks

Study Arms (3)

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

Interventions

50 mg AP1189 DRUG

50 mg AP1189 powder in bottle

Also known as: AP1189

50 mg AP1189

AP1189 DRUG

100 mg AP1189 powder in bottle

100 mg AP1189

Placebo DRUG

Placebo powder in bottle

Placebo

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• SynAct Pharma Aps: lead

Study Sites (2)

Aarhus Universitetshospital

Aarhus, 8200, Denmark

Location

Diakonhjemmet Sykehus

Oslo, 0370, Norway

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

N-(3-(1-(2-nitrophenyl)-1H-pyrrol-2-yl)allylidenamino)guanidine

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Thomas Jonassen, Chief Scientific Officer
• Organization: SynAct Pharma

tj@SynActpharma.com

+45 4015 6669

Study Officials

• Ellen-Margrethe Hauge, Professor

  Aarhus University Hospital

  PRINCIPAL INVESTIGATOR

• Espen A Haavardsholm, Concultant, PhD

  Diakonhjemmet Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multicenter, two-part, randomized, double-blind, placebo-controlled 4-week study with repeated doses of AP1189

Study Record Dates

• First Submitted: June 26, 2019
• First Posted: July 2, 2019
• Study Start: August 26, 2019
• Primary Completion: November 16, 2021
• Study Completion: November 16, 2021
• Last Updated: July 10, 2024
• Results First Posted: July 10, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1); NO (1)