A Study To Evaluate The Efficacy And Safety Of Intravenous Nanocort Compared With A Intramuscular Injection of Methylprednisolone Acetate In Patients With Rheumatoid Arthritis

• Register: EUCTR
• Last refreshed on: 23 July 2018
• Main ID: EUCTR2015-002924-17-BE
• Date of registration: 27/01/2016
• Prospective Registration: Yes
• Primary sponsor: Sun Pharma Global FZE
• Public title: A Study To Evaluate The Efficacy And Safety Of Intravenous Nanocort Compared With A Intramuscular Injection of Methylprednisolone Acetate In Patients With Rheumatoid Arthritis
• Scientific title: A Phase III, Randomized, Double-Blind, Double Dummy, Active Controlled, Multi-Center Study To Evaluate The Efficacy And Safety Of Intravenous Pegylated Liposomal Prednisolone Sodium Phosphate (Nanocort) Compared With Intramuscular Injection Of Methylprednisolone Acetate In Subjects With Active Rheumatoid Arthritis
• Date of first enrolment: 24/02/2016
• Target sample size: 330
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-002924-17
• 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: yes; Other trial design description: dubble dummy; If controlled, specify comparator, Other Medicinial Product: yes; Placebo: no; Other: no; Number of treatment arms in the trial: 3
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Netherlands

Contacts

• Name: Manager Business Development
• Affiliation: Sun Pharma Global FZE

• Name: Manager Business Development
• Affiliation: Sun Pharma Global FZE

Key inclusion & exclusion criteria

Inclusion criteria:
1) Male or female = 18 years old.
2) Known Diagnosed RA according to the revised 2010 ACR/EULAR Rheumatoid Arthritis Classification Criteria. Secondary Sjögren’s syndrome with RA is permitted.
3) Male and female subjects with active RA who are experiencing a flare / exacerbation defined as a recent increase in symptoms and a measured increase in DAS28 > 1.2 or > 0.6 if DAS28 = 3.2 compared to last DAS28 measurement (maximum 6 months before). The increase in DAS28 has to be RA related.
4) Willing and able to comply with the study protocol visits, assessments and accessible for follow up.
5) Subjects naïve to treatment and/or currently not treated for at least 8 Weeks prior to the Screening Visit and willing to continue without non-study treatment for 12 Weeks, or subjects on stable treatment with DMARD (including biologicals) for at least 8 Weeks prior to the Screening Visit and willing to continue current stable treatment for 12 Weeks.
6) Subjects able and willing to give written informed consent (or legally acceptable representative or impartial witness when applicable) and is available for entire study.
7) Subjects of child bearing potential should be non-lactating and must be practicing an acceptable method of birth control as judged by the Investigator. Medically acceptable methods of birth control include bilateral tubal ligation or the use of either a contraceptive implant, a contraceptive injection (e.g., Depo Provera™), an intrauterine device, vasectomized partner, an oral contraceptive taken continually within the past three months and which the subject agrees to continue using during the study.
8) Male subjects enrolled in the study are advised to prevent passage of semen to their sexual partner during intercourse using acceptable methods as judged by the investigator.

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 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion criteria:
1) Rheumatic autoimmune disease other than RA, e.g., systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleroderma, polymyositis.
2) Current inflammatory joint disease other than RA (e.g., gout, reactive arthritis, psoriatic arthritis, spondyloarthritis, Lyme disease, osteoarthritis).
3) Subjects who are pregnant or intend to become pregnant during the study.
4) Have a family history (more than one first degree relative) of multiple thrombotic events or a personal history of any venous or arterial thrombotic event including deep vein thrombosis, stroke, myocardial infarction, pulmonary embolus, and peripheral arterial thromboembolic events or abnormal ECG which may impact the subject’s safety as per Investigator’s opinion.
5) Subject with positive hepatitis panel (including hepatitis B surface antigen [HBsAg], and / or anti-hepatitis B core antibodies, and / or hepatitis C virus antibody [anti-HCV]), and / or a positive Human immunodeficiency virus (HIV) antibody screen, based on the current medical data of the patient.
6) Abnormal hepatic function [alanine aminotransferase (ALT)/aspartate aminotransferase (AST) or bilirubin > 2 x upper limit of normal] at the time of the Screening Visit.
7) Abnormal renal function [Blood Urea Nitrogen (BUN) or creatinine >1.25 x upper limit of normal] at the time of the Screening Visit.
8) Clinically significant out-of-range values on hematology panel, at discretion of the PI.
9) Treatment with oral, rectal or injectable (including intra-articular) glucocorticoids (GCs) within 8 Weeks prior to Screening Visit. Inhaled glucocorticoids are allowed. Topical steroids are allowed, however subjects should not have received more than 100 gram of a mild to moderate topical corticosteroid cream per Week, 50 gram of a potent corticosteroid cream per Week or 30 gram of a very potent topical corticosteroid cream per Week in the 4 Weeks prior to the Screening Visit.
10) Subjects who have received an investigational drug within 30 Days prior to the Screening visit.
11) Previous treatment with IV gamma globulin, plasmapheresis or Prosorba® column within 3 months prior to Screening.
12) Known sensitivity to any component of the study drug or previous hypersensitivity reaction or other clinically significant reaction to IV medications, biologic therapy or IV radiocontrast agents.
13) Contraindication for glucocorticoids as judged by Investigator.
14) Subjects who have previously received Nanocort.
15) Neuropathies or other painful conditions that might interfere with pain evaluation, as judged by the Investigator.
16) Active infection requiring systemic treatment.
17) Planned surgery during the study period or had undergone major surgery within the 60 Days prior to the Screening visit.
18) Requirement for immunizations or vaccinations during the study period.
19) Subjects with poor peripheral venous access as per Investigator or site personnel opinion.
20) History of substance abuse or alcohol abuse.

Additional exclusion criteria for subjects participating in PK subset study:
Blood donation by subjects within 6 months before screening.




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

Health Condition(s) or Problem(s) studied

Active Rheumatoid Arthritis

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: Nanocort
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: prednisolone
Other descriptive name: PREDNISOLONE
Concentration unit: mg milligram(s)
Concentration type: up to
Concentration number: 150-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Trade Name: Depo Medrol
Product Name: Depo Medrol
Pharmaceutical Form: Suspension for injection
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intramuscular use

Primary Outcome(s)

Primary end point(s): Primary Endpoint: European League Against Rheumatism (EULAR) responder (moderate and good combined) rate at Week 1 (Day 8)

Secondary Objective: Patient Reported Outcomes and an assessment of pharmacokinetic parameters in a subset population from each treatment group.

Main Objective: To assess efficacy and safety (treatment of signs and symptoms) of Nanocort in subjects with active rheumatoid arthritis who are experiencing a flare/exacerbation in comparison to a standard of care medication (Depo-Medrol).

Timepoint(s) of evaluation of this end point: Week 1 (Day 8)

Secondary Outcome(s)

Secondary end point(s): Key Secondary Endpoints:
• EULAR responder (only good) rate at Week 1 (Day 8)
• EULAR responder (moderate and good combined) rate at Week 2 (Day 15)
• EULAR responder (only good) rate at Week 2 (Day 15)

Secondary endpoints:
• EULAR response at Week 1, 2, 3, 4, 6, 8 and 12
• DAS28 mean and % change at Week 1, 2, 3, 4, 6, 8 and 12
• Time to first EULAR response (moderate/good)
• ACR 20/50/70 response scores at Week 1, 2, 3, 4, 6, 8 and 12
• Tender joint counts at Week 1, 2, 3, 4, 6, 8 and 12
• Swollen joint counts at Week 1, 2, 3, 4, 6, 8 and 12
• Patient pain and Global Visual Analog Score (VAS) score at Week 1, 2, 3, 4, 6, 8 and 12
• Investigator Global Visual Analog Score (VAS) score at Week 1, 2, 3, 4, 6, 8 and 12
• Short Form 36 (SF-36) to assess physical and mental component at Week 1, 2, 4, 6, and 12.
• Health Assessment Questionnaire (HAQ) at Week 1, 2, 3, 4, 6, 8 and 12.
• The Functional Assessment of Chronic Illness Therapy (FACIT) at Baseline, Week 4 and 6
• Health Economics Questionnaire at Week 12
• Maintenance of Improvement at 12 Weeks assessed during a blinded review by the Medical Monitor (MM) and Principal Investigator (PI) at the end of the study
• AEs (including glucocorticoid related AEs, AEs leading to withdrawal, AEs leading to discontinuation of medication, and AEs due to infusion reactions)
• Vital signs
• Physical examinations
• Laboratory
• ECG
• Pharmacokinetics assessment in subset of patient population at Baseline, Week 1, 2, 3, 4 and 6
• Assessment by monitoring cortisol levels at Screening, Baseline, 6 and 12 weeks

Timepoint(s) of evaluation of this end point: see E.5.2

Secondary ID(s)

2015-002924-17-NL

NCT02534896

CLR_15_05

Source(s) of Monetary Support

Sun Pharma Global FZE