A multicenter, placebo-controlled phase II study to evaluate safety and clinical efficacy of two different doses of F8IL10 administered subcutaneously to patients with active rheumatoid arthritis receiving Methotrexate.

• Register: EUCTR
• Last refreshed on: 12 March 2024
• Main ID: EUCTR2013-005418-37-IT
• Date of registration: 06/03/2014
• Prospective Registration: Yes
• Primary sponsor: Philogen S.p.A.
• Public title: A multicenter, placebo-controlled phase II study to evaluate safety and clinical efficacy of two different doses of F8IL10 administered subcutaneously to patients with active rheumatoid arthritis receiving Methotrexate.
• Scientific title: A multicenter, randomized, double-blind, placebo-controlled phase II study to evaluate safety and clinical efficacy of two different doses of F8IL10 (Dekavil) administered subcutaneously to patients with active rheumatoid arthritis receiving Methotrexate.
• Date of first enrolment: 15/09/2014
• Target sample size: 87
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-005418-37
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany, Italy

Contacts

• Name: NA
• Affiliation: Philogen S.p.A,

• Name: NA
• Affiliation: Philogen S.p.A,

Key inclusion & exclusion criteria

Inclusion criteria:
1.Patients aged =18 and < 75 years.
2.Diagnosis of RA according to ACR/EULAR classification criteria (2010) with a disease duration exceeding 6 months.
3.Active RA (DAS28 = 3.2) for = 3 months at time of signing informed consent despite MTX therapy (stable regimen of 10-25 mg/week for at least 8 weeks before screening).
4.=6 tender joints out of 68, =6 swollen joints out of 66 and serum CRP > 0.5 mg/dl at screening
5.History of inadequate clinical response to at least one anti-TNF drug (applied for at least 3 months).
6.Stable regimens of NSAIDs and/or oral corticosteroid (= 10 mg/day; prednisone equivalent) for a period = 2 weeks prior to screening.
7.All acute toxic effects of any prior therapy must have returned to classification “mild” according to CTCAE v.4.03 (published on June 14th 2010).
8.Sufficient hematologic, liver and renal function:
•Absolute neutrophil count (ANC) = 1.5 x 10^9/L, platelets =100 x10^9/L, haemoglobin (Hb) = 10.0 g/dL.
•Alkaline phosphatase (AP), alanine aminotransferase (ALT) and or aspartate aminotransferase (AST) = 3 x upper limit of normal range (ULN), and total bilirubin = 2.0 mg/dl (34.2 µmol/L).
•Creatinine = 1.5 ULN or 24 h creatinine clearance = 50 mL/min.
9.Documented negative test for HIV, HBV and HCV. For patients with serology documenting previous exposure to HBV (i.e., anti-HBs Ab with no history of vaccination and/or anti-HBc Ab) , negative serum HBV DNA is required.
10.Male and female patients, who are potentially fertile, must agree to use adequate contraceptive methods at the beginning of the screening visit that must be continued until 3 months following the last treatment with study drug.
11.Negative serum pregnancy test (for women of child-bearing potential only) at screening.
12.Signed and dated Ethics Committee-approved Informed Consent Form indicating that the patient has been informed of all pertinent aspects of the study.
13.Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures.

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 70
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 17

Exclusion criteria:
1.Presence of active infections or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or would interfere with the study objectives or conduct.
2.Pregnancy, lactation or unwillingness to use adequate contraceptive methods.
3.Diagnosis of any other inflammatory arthritis or active autoimmune diseases other than RA.
4.Last treatment with monoclonal antibodies (i.e., adalimumab, infliximab, golimumab, tocilizumab, certolizumab pegol) less than 8 weeks prior to first administration of study drugs. Last treatment with rituximab less than 16 weeks prior to first administration of study drugs. Last treatment with fusion proteins (i.e., abatacept, etanercept) less than 4 weeks prior to first administration of study drugs.
5.Treatment with any immunosuppressant drug other than MTX and corticosteroids.
6.Active or latent tuberculosis (TB).
7.HIV infection.
8.Acute or chronic HBV or HCV infection, as assessed by serology or serum HBV DNA .
9.History or currently active primary or secondary immunodeficiency.
10.Concurrent malignancy or history of malignancy from which the patient has been disease–free for less than 5 years.
11.History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
12.Treatment with warfarin or other coumarin derivatives.
13.Hearth insufficiency (> Grade II, NYHA criteria).
14.Irreversible cardiac arrhythmias requiring permanent medication.
15.Clinically significant (to clinical investigator’s discretion) abnormalities in baseline ECG analysis.
16.Uncontrolled hypertension.
17.Ischemic peripheral vascular disease (Grade IIb-IV).
18.Severe diabetic retinopathy.
19.Major trauma including surgery within 4 weeks prior to administration of study treatment.
20.Known history of allergy or other intolerance to IL10, methotrexate, folic acid or other drugs based on human proteins/peptides/antibodies.
21.Treatment with any investigational agent within the 6 weeks before study treatment.
22.Immunization with a live/attenuated vaccine within 4 weeks prior to baseline or plan to receive vaccines during the study.
23.Treatment with growth factors or immunomodulatory agents, including Anakinra, within 7 days of the administration of study drugs.
24.Chronic pain disorders (not RA-related) that might interfere with pain evaluation.
25.Patients requiring stable doses of corticosteroids > 10 mg/day (prednisone equivalent). Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterion.
26.Concurrent intra-articular corticosteroids treatment or patient who have received it within 2 weeks prior to randomization.
27.History of alcohol, drug or chemical substance abuse within the 6 months prior to screening.
28.Any condition that in the opinion of the investigator could hamper compliance with the study protocol.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Patients with active Rheumatoid Arthritis despite methotrexate therapy that had unsuccessful response to at least one anti-TNF treatment.

Intervention(s)

Product Name: Dekavil
Product Code: F8IL10
Pharmaceutical Form: Solution for injection
INN or Proposed INN: dekavil
Current Sponsor code: F8IL10
Other descriptive name: F8IL10
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 3.75-20
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: week 9

Main Objective: Mean change from baseline in DAS28-CRP between F8IL10 and placebo arms at week 9.

Primary end point(s): Mean change from baseline in DAS28-CRP between F8IL10 and placebo arms at week 9.

Secondary Objective: -Safety and tolerability of subcutaneous F8IL10 when administered in combination with MTX.
- Proportion of patients achieving an ACR clinical response (ACR20, 50 and 70) and time to onset of these criteria.
- Proportion of patients achieving clinical remission and clinical low- disease activity according to DAS 28-CRP (DAS28 < 2.6 and 2.6= DAS28 <3.2 , respectively) and time to onset of these criteria.
- Proportion of patients achieving clinical remission and clinical low-disease activity according to SDAI score (SDAI = 3.3 and SDAI = 11.0) and time to onset of these criteria.
- Proportion of patients that experienced significant change from baseline in functional status (HAQ-DI and SF-36).
- Maintenance of clinical response (ACR, DAS28 and SDAI scores).
- Immunogenicity of F8IL10 (HAFA formation).
- Pharmacodynamic profile of F8IL10.

Secondary Outcome(s)

Secondary end point(s): -Safety and tolerability of subcutaneous F8IL10 when administered in combination with MTX.
-Proportion of patients achieving an ACR clinical response (ACR20, 50 and 70) and time to onset of these criteria.
-Proportion of patients achieving clinical remission and clinical low- disease activity according to DAS 28-CRP (DAS28 < 2.6 and 2.6= DAS28 <3.2, respectively) and time to onset of these criteria.
-Proportion of patients achieving clinical remission and clinical low-disease activity according to SDAI score (SDAI = 3.3 and SDAI = 11.0) and time to onset of these criteria.
-Proportion of patients that experienced significant change from baseline in functional status (HAQ-DI and SF-36).
-Maintenance of clinical response (ACR, DAS28 and SDAI scores).
-Immunogenicity of F8IL10 (HAFA formation).
-Pharmacodynamic profile of F8IL10.

Timepoint(s) of evaluation of this end point: Safety and tolerability: every study visit during all the study
Proportion of patients achieving an ACR clinical response (ACR20, 50 and 70): Every week during treatment and every 4 weeks after EOT
Patients achieving clinical remission and clinical low- disease activity according to DAS 28-CRP and SDAI : Every week during treatment and every 4 weeks after EOT
Patients that experienced significant change from baseline in functional status (HAQ-DI and SF-36): Week 9 (EOT) and every 4 weeks after EOT
Maintenance of clinical response (ACR, DAS28 and SDAI scores): every 4 weeks after W9 or EOT
PD: screening, week 1, 5, 9, all FU visits
F8IL10 HAFA formation: screening, week 1, 5, 9, all FU visits

Secondary ID(s)

PH-F8IL10-03/13

Source(s) of Monetary Support

Philogen S.p.A.

Ethics review

Status: Approved
Approval date: 15/09/2014
Contact: