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A Randomized, Placebo-controlled Phase II Clinical Trial to Evaluate the Safety and Efficacy of F8IL10 (Dekavil) in Patients With Active RA Receiving MTX

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02270632
Recruitment Status : Unknown
Verified October 2016 by Philogen S.p.A..
Recruitment status was:  Recruiting
First Posted : October 21, 2014
Last Update Posted : November 28, 2016
Sponsor:
Information provided by (Responsible Party):
Philogen S.p.A.

Brief Summary:
A multicenter, randomized, parallel assignment, double blind, placebo-controlled, safety/efficacy phase II study of two different dosages of subcutaneous F8IL10 in patients with active rheumatoid arthritis receiving MTX.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: F8IL10 Drug: MTX Drug: Placebo Phase 2

Detailed Description:

The study is designed to formally demonstrate the superiority of F8IL10 vs placebo and to further evaluate safety and efficacy of two different dosages of F8IL10 when administered to patients receiving MTX.

Patients will be enrolled and double-blind, parallel assigned (via automated randomization system) in a 1:1:1 fashion to one of three different arms:

  • Arm 1: placebo + MTX
  • Arm 2: F8IL10 30 µg/kg + MTX
  • Arm 3: F8IL10 160 µg/kg + MTX

F8IL10 or placebo will be subcutaneously injected once a week for 8 weeks. Treatment will terminate at the earliest of the following: completion of the 8 weeks of therapy, withdrawal of informed consent, unacceptable toxicity/intolerability of the study drug or need to increase MTX, oral corticosteroids or NSAIDs dosages above baseline levels or need to introduce a new DMARD or biologic therapy to control rheumatoid arthritis activity. The study will be conducted in a double blind fashion.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 87 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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.
Study Start Date : October 2014
Estimated Primary Completion Date : April 2018
Estimated Study Completion Date : April 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Arm 1
Placebo
Drug: MTX
All patients enrolled in the study will receive as concomitant therapy MTX at stable dose (10-25 mg/week), and the corresponding fixed dose of folic acid.
Other Name: Methotrexate

Drug: Placebo
Placebo will be administered once a week for 8 weeks (or until withdrawn from the study).

Experimental: Arm 2
F8IL10, 30 μg/kg
Drug: F8IL10
F8IL10 will be administered once a week for 8 weeks (or until withdrawn from the study).
Other Name: Dekavil

Drug: MTX
All patients enrolled in the study will receive as concomitant therapy MTX at stable dose (10-25 mg/week), and the corresponding fixed dose of folic acid.
Other Name: Methotrexate

Experimental: Arm 3
F8IL10, 160 μg/kg
Drug: F8IL10
F8IL10 will be administered once a week for 8 weeks (or until withdrawn from the study).
Other Name: Dekavil

Drug: MTX
All patients enrolled in the study will receive as concomitant therapy MTX at stable dose (10-25 mg/week), and the corresponding fixed dose of folic acid.
Other Name: Methotrexate




Primary Outcome Measures :
  1. Change from baseline in DAS28-CRPscore [ Time Frame: At week 9 ]
    Mean change from baseline in DAS28-CRP between F8IL10 and placebo arms.


Secondary Outcome Measures :
  1. Number of Participants with Adverse Events [ Time Frame: Up to 8 months from randomization ]
    Safety and tolerability of subcutaneous F8IL10 when administered in combination with MTX.

  2. Response rate according to ACR and EULAR criteria [ Time Frame: 1) week 9; 2) from week 12 up to week 32, every 4 weeks ]
    Proportion of patients achieving an ACR clinical response (ACR20, 50 and 70) and time to onset of these criteria.

  3. Clinical Remission and low-disease activity (DAS28-CRP) [ Time Frame: 1) week 9; 2) from week 12 up to week 32, every 4 weeks ]
    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.

  4. Clinical Remission and low-disease activity (SDAI score) [ Time Frame: 1) week 9; 2) from week 12 up to week 32, every 4 weeks ]
    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

  5. Absolute count and change from baseline in tender and swollen joint counts [ Time Frame: 1) from week 1 up to week 9; 2) from week 12 up to week 32, every 4 weeks ]

    The tender joint count represents the number of joints in which pain is reported at rest with pressure or on movement.

    The swollen joint count represents the number of joints in which there is synovial fluid and/or soft tissue swelling.


  6. Absolute score and change from baseline in physician's and patient's global assessments of disease activity (100 mm VAS) [ Time Frame: 1) from week 1 up to week 9; 2) from week 12 up to week 32, every 4 weeks ]
    Patient's and Physician's global assessment of disease activity.

  7. Absolute score and change from baseline in patient assessment of the pain intensity at each visit (100 mm VAS) [ Time Frame: 1) from week 1 up to week 9; 2) from week 12 up to week 32, every 4 weeks ]
    Patient's assessment of pain.

  8. Proportion of patients that experienced significant change from baseline in functional status (HAQ-DI) [ Time Frame: 1) week 9; 2) from week 12 up to week 32, every 4 weeks ]
  9. Proportion of patients that experienced significant change from baseline in functional status (SF-36) [ Time Frame: 1) week 9; 2) from week 12 up to week 32, every 4 weeks ]
  10. HAQ score and change from baseline in HAQ score [ Time Frame: 1) week 1; 2) week 9; 3) from week 12 up to week 32, every 4 weeks ]
  11. Inflammatory parameters CRP or ESR and change from baseline [ Time Frame: 1) from week 1 up to week 9; 2) from week 12 up to week 32, every 4 weeks ]
    Laboratory assessments (CRP, ESR)

  12. Human anti-fusion protein antibodies (HAFA) levels [ Time Frame: 1) day 14 - 0 (screening); 2) at week 1; 3) at week 5; 4) at week 9 (EoT); 5) from week 12 up to week 32, every 4 weeks ]
    Investigate the potential induction of human anti-fusion protein antibodies (HAFA) through standard laboratory analysis.

  13. Percentage of Participants With Worst On-Study Hematological and Chemistry Abnormalities [ Time Frame: 1) from week 1 up to week 9; 2) from week 12 up to week 32, every 4 weeks ]
  14. Clinically Meaningful Changes in Vital Signs and Physical Examinations [ Time Frame: 1) from week 1 up to week 9; 2) from week 12 up to week 32, every 4 weeks ]
  15. Changes in absolute counts and relative percentages of main biomarker/cytokines [ Time Frame: 1) day 14 - 0 (screening); 2) at week 1; 3) at week 5; 4) at week 9 (EoT); 5) from week 12 up to week 32, every 4 weeks ]
    Biomarkers :IgA, IgE, Soluble IL-2 receptor, Soluble IL-1 receptor antagonist, MMP3); cytokines: IL-1α, IL-1β, TNFα, IL2, IL6, IL17, IL18, IL22, VEGF



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 74 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

At the time of enrolment, patients must fulfil all of the following 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 methotrexate 10-25 mg/week orally, subcutaneous or intramuscular injections: stable dosage from ≥ 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 14, 2010).
  8. Sufficient hematologic, liver and renal function:

    • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥100 x109/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. All female subjects must have negative pregnancy test results at the screening. Women of childbearing potential must be using simultaneously double-barrier or two acceptable methods of contraception (i.e. intra-uterine device plus condom, spermicidal gel plus condom, diaphragm plus condom, etc.) from the screening to three months following the last study drug administration. Pregnancy test will be repeated at the end of treatment visit.
  11. Male patients must agree to use simultaneously two acceptable methods of contraception (i.e. spermicidal gel plus condom) from the screening to three months following the last study drug administration.
  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.
  14. Chest X rays performed (for other reasons than the present clinical trial) within a period of 3 months prior to the screening visit. However, in the case the patient performs the Quantiferon TB test during the screening visit, this period can be extended to 6 months.

Exclusion Criteria

Patients must not be enrolled into the study if, at the time of enrolment, they have any of the following:

  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. Heart 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02270632


Contacts
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Contact: Franziska Bootz, PhD +39 0577 17816 regulatory@philogen.com
Contact: Serena Bettarini, Dr +39 0577 17816 regulatory@philogen.com

Locations
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Germany
Universitatsklinikum Essen Recruiting
Essen, Germany
Principal Investigator: Christof Specker, Prof.         
Universitatsklinikum Freiburg Recruiting
Freiburg, Germany
Principal Investigator: Reinhard Voll, MD         
Schön Klinik Hamburg Eilbek Recruiting
Hamburg, Germany
Principal Investigator: Jürgen Wollenhaupt, Prof         
Italy
Ospedale Luigi Sacco, Milano Recruiting
Milano, Italy
Principal Investigator: Piercarlo Sarzi Puttini, Prof.         
Azienda Ospedaliera Universitaria Senese Recruiting
Siena, Italy
Principal Investigator: Mauro Galeazzi, Prof.         
Azienda Ospedaliera Universitaria Integrata Verona Recruiting
Verona, Italy
Principal Investigator: Ombretta Viapiana, Dr         
Switzerland
HFR Fribourg - Hôpital Cantonal Recruiting
Fribourg, Switzerland
Principal Investigator: Jean Dudler, MD         
Centre Hospitalier Universitaire Vaudois Recruiting
Lausanne, Switzerland
Principal Investigator: Zufferey Pascal, MD         
Sponsors and Collaborators
Philogen S.p.A.
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Responsible Party: Philogen S.p.A.
ClinicalTrials.gov Identifier: NCT02270632    
Other Study ID Numbers: PH-F8IL10-03/13
First Posted: October 21, 2014    Key Record Dates
Last Update Posted: November 28, 2016
Last Verified: October 2016
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors