A clinical study to evaluate the tolerability of repeated doses of CEP-33457 administered in patients with a chronic autoimmune disease (Lupus)

• Register: EUCTR
• Last refreshed on: 10 March 2014
• Main ID: EUCTR2010-019293-32-PT
• Date of registration: 26/07/2010
• Prospective Registration: Yes
• Primary sponsor: Cephalon, Inc.
• Public title: A clinical study to evaluate the tolerability of repeated doses of CEP-33457 administered in patients with a chronic autoimmune disease (Lupus)
• Scientific title: An Open-Label Long-Term Study of the Safety and Tolerability of Repeated administration of CEP-33457 in Patients With Systemic Lupus Erythematosus - Celestial 75
• Date of first enrolment: 01/10/2010
• Target sample size: 130
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019293-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 1

Countries of recruitment

Belgium, Czech Republic, Germany, Hungary, Poland, Portugal, Spain, Ukraine, United States

Contacts

• Name: Brian Dove
• Affiliation: PPD

• Name: Brian Dove
• Affiliation: PPD

Key inclusion & exclusion criteria

Inclusion criteria:
Patients are included in the study if all of the following criteria are met:
(a1) The patient previously participated in and completed at least visit 8 (week 24) in the Cephalon-sponsored clinical study with CEP-33457 (study C33457/2047) and, in the investigator's opinion, would benefit from continued participation in a clinical study.
(b) The patient is a man or woman between 18 and 70 years of age who has an established diagnosis of SLE as defined by ACR Classification Revised Criteria. The diagnosis is fulfilled provided that at least 4 criteria are met.
(c) Written informed consent is obtained.
(d) Women must be surgically sterile, 2 years postmenopausal, or, if of childbearing potential, using a medically accepted method of contraception and must agree to continued use of this method for the duration of the study and for 30 days after discontinuation of study drug treatment. Acceptable methods of contraception include barrier method with spermicide, abstinence, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected) in conjunction with a barrier method.
(e) The patient must be willing and able to comply with study restrictions, to remain at the clinic for the required duration during the study period, and to return to the clinic for the final assessment as specified in this protocol.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 126
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion criteria:
Patients are excluded from participating in this study if 1 or more of the following criteria are met:
(a) The patient has New York Heart Association (NYHA) Class III or IV
congestive heart failure
(b) The patient has an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73m2 (via Modification of Diet in Renal Disease [MDRD] equation).
(c) The patient has an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value greater than 2 times the upper limit of the normal range (ULN) or a total bilirubin value of greater than or equal to 1.5 times the ULN.
(d) The patient has a planned immunization with a live or live attenuated vaccine within 3 months prior to the 1st dose of study drug and for 3 months after administration of the last dose of study drug is administered.
(e) The patient has clinically significant abnormalities on the 12 lead EGG that are not related to SLE, as determined by the investigator. Patients with stable ECG changes without evidence of active cardiovascular disease may participate at the discretion of the investigator and medical monitor.
(f) The patient has an ongoing active systemic infection requiring treatment or a history of severe infection, such as hepatitis or pneumonia, in the 3 months prior to administration of the 1st dose of study drug. Patients with a history of less severe infections in the 3 months prior to administration of the 1st dose of study drug are permitted to participate in the study at the discretion of the investigator and medical monitor.
(g) The patient has any concomitant medical condition unrelated to SLE that may interfere with his or her safety or with evaluation of the study drug, as determined by the investigator.
(h1) The patient has a history of a positive test result for hepatitis B surface antigen (HBsAg) or hepatitis C virus antibody (HCV Ab).
(i) The patient has a known positive history of antibodies to human immunodeficiency virus (HIV) or HIV disease.
(j) The patient has a history of alcohol or substance dependence or abuse (with the exception of nicotine), according to the Diagnostic and Statistical Manual of Mental Disorders of the American Psychiatric Association, Fourth Edition, Text Revision (DSM IV TR), within 3 months of the screening visit for study C33457/2047, or current substance abuse.
(k) The patient has a history of severe allergic reactions to or hypersensitivity to any component of the study drug.
(l) The patient is a pregnant or lactating woman. (Any women becoming pregnant during the study will be withdrawn from the study.)
(m) The patient has undergone or is undergoing treatment with another investigational drug for the treatment of lupus within 6 months prior to the 1st dose of study drug or has received any other investigational drug for any other condition within 30 days prior to the 1st dose of study drug, except for treatment with CEP-33457 or placebo in study 33457/2047.
(n1) The patient has a known history of antibodies to CEP-33457.
(o) The patient is unlikely to comply with the study protocol or is unsuitable for any other reason, as judged by the investigator or medical monitor




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

Health Condition(s) or Problem(s) studied

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

Patients With Systemic Lupus Erythematosus (SLE)
MedDRA version: 14.1 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders

Intervention(s)

Product Name: Lupuzor
Product Code: CEP-33457
Pharmaceutical Form: Powder for injection
INN or Proposed INN: Forigerimod
CAS Number: 1160237-55-7
Current Sponsor code: CEP-33457
Other descriptive name: IPP-201101, P140
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Primary end point(s): Safety is the primary objective of this study and will be assessed by
evaluating the following:
• occurrence of adverse events throughout the study
• clinical laboratory tests (serum chemistry, hematology, and urinalysis) at each visit during the treatment period
• vital signs (systolic and diastolic blood pressures, pulse, temperature, and body weight) measurements at each visit during the treatment period
• 12 lead ECG at week 48 and the final assessment (or early termination)
• physical examination findings, including physical examination symptom directed findings, at selected time points throughout the study
• concomitant medication usage throughout the study

Timepoint(s) of evaluation of this end point: Please refer to section E.5.1

Main Objective: The primary objective of the study is to evaluate the long term safety and tolerability of repeated administration of subcutaneous (sc) CEP 33457 every 4 weeks over 72 weeks in patients with systemic lupus erythematosus (SLE) who have participated in a previous Cephalon sponsored clinical study of CEP-33457.
Safety will be assessed by evaluating the following:
•occurrence of adverse events
•clinical laboratory tests (serum chemistry, hematology, and urinalysis)
•vital signs (blood pressures, pulse, temperature, and body weight)
measurements
•12 lead ECG
•physical examination findings, including physical examination symptom
directed findings
•concomitant medication usage

Secondary Objective: The secondary objectives of the study are the following:
•SRI response
•change in SLEDAI 2K score
•change in BILAG 2004 score
•status of disease (PhGA and Patient’s Global Assessment [PtGA] scales)
•health related QoL (SF 36 Questionnaires)
•biologic markers of disease activity (eg serology B [autoantibodies, complement components, mmunoglobulins, interleukins]) and immunophenotyping)
•incidence of disease flares (eg SELENA Flare Index)
•occurrence of SLE induced organ damage, (eg SLICC/ACR Damage Index)
•remission of disease (ie SLEDAI 2K score reduction to 0)
•changes in steroid dose

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Please refer to section E.5.2

Secondary end point(s): The efficacy variables and endpoints for this study are to determine the following:
• proportion of patients achieving a clinical response using the SRI at each visit during the treatment period.
• change in SLEDAI-2K score at each visit during the treatment period
• change in BILAG-2004 score at each visit during the treatment period
• proportion of patients showing no worsening on PhGA scale at each visit during the treatment period
• proportion of patients showing no worsening on PtGA scale at weeks 12, 24, 36, 48, and 60 and the final assessment (or early termination)
• changes in SF-36 at weeks 12, 24, 36, 48, and 60 and the final assessment (or early termination)
• changes in the biomarkers anti-dsDNA Ab and C3 and C4 at each visit during the treatment period
• changes in the following biomarkers at weeks 12, 24, 36, 48, and 60 and the final assessment (or early termination): anti-U1RNP Ab, anti-Sm Ab, CRP, IgG, IgM, IgE, and ANA
• SELENA Flare Index at each visit
• changes in the SLICC/ACR Damage Index score at weeks 24 and 48 and the final assessment (or early termination)
• remission of disease (ie, reduction of SLEDAI-2K score to 0)
• proportion of patients with changes in steroid dose over time throughout the study
The immunogenicity variable and endpoint for this study are as follows: any presence of anti–CEP-33457 Ab at weeks 24 and 48 and the final assessment (or early termination).

Secondary ID(s)

2010-019293-32-DE

C33457/3075

Source(s) of Monetary Support

Cephalon Inc.