A multi-center, double-blind, placebo-controlled, proof-of-concept study to evaluate the efficacy and tolerability of KRP203 in patients with active subacute cutaneous lupus erythematosus. - ND

• Register: EUCTR
• Last refreshed on: 28 August 2012
• Main ID: EUCTR2010-019689-10-IT
• Date of registration: 04/11/2010
• Prospective Registration: No
• Primary sponsor: NOVARTIS FARMA
• Public title: A multi-center, double-blind, placebo-controlled, proof-of-concept study to evaluate the efficacy and tolerability of KRP203 in patients with active subacute cutaneous lupus erythematosus. - ND
• Scientific title: A multi-center, double-blind, placebo-controlled, proof-of-concept study to evaluate the efficacy and tolerability of KRP203 in patients with active subacute cutaneous lupus erythematosus. - ND
• Date of first enrolment: 22/10/2010
• Target sample size: 24
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-019689-10
• 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

Countries of recruitment

Germany, Greece, Italy

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male and female patients between 18-65 (inclusive) years of age who have been defined as having SCLE based on the typical clinical picture and the characteristic histopathological features as described by Sontheimer et al. at least three months before study entry (screening). 2. The patients must demonstrate moderate to severe active skin disease at baseline by having an activity score of CLASI = 6, with at least 2 points in at least 3 different anatomical locations for erythema or scale/hypertrophy. 3. Patients must have failed systemic therapy such as a full dose of an antimalarial agent (hydroxychloroquine, chloroquine or quinacrine) or a combination of lower doses of antimalarials, prior to screening. A failed response is considered to be one or more of the following: inadequate clinical response after at least 12 weeks of therapy; loss of clinical response to antimalarial therapy; toxicity in response to antimalarial therapy that required discontinuation of treatment. 4. If the patient is on oral corticosteroids at screening, the dose (max. 5 mg prednisone or equivalent per day) must be stable from at least 2 weeks prior to screening (and for the duration of the study). 5. Female patients may be included in the study according to the following: a. Female patients of child bearing potential must be using two highly effective methods of contraception (one primary and one secondary), from the time of screening and for the duration of the study, through Study Completion and for two (2) months after study completion. Period abstinence (e.g., calendar, ovulation, symptothermal, post- ovulation methods) and withdrawal are not acceptable methods of contraception. b. Postmenopausal females must have had no regular menstrual bleeding for at least one (1) year prior to initial dosing. Menopause will be confirmed by a plasma FSH level of >40 IU/L at screening. c. Female patients who report surgical sterilization must have had the procedure at least six (6) months prior to initial dosing. Surgical sterilization procedures should be supported with clinical documentation made available to the sponsor and noted in the Relevant Medical History / Current Medical Conditions section of the CRF. d. All female patients must have negative pregnancy test results at Screening and baseline. 6. Male subjects must agree to comply with two highly effective contraceptive methods comprising a barrier method (condom or occlusive cap plus spermicidal) for up to the last drug administration, and refrain from fathering a child for at least two (2) months following the last study drug administration. Periodic abstinence and withdrawal are not acceptable methods of contraception. 7. Patients must be able to communicate well with the Investigator, to understand and comply with the requirements of the study and to understand and sign the written informed consent.
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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Patients with preexisting nephritis, central nervous or pulmonary involvement or any major internal organ damage, either related or unrelated to lupus, which are deemed by the Investigator to be clinically significant. Patients having signs or symptoms of other autoimmune diseases such as systemic lupus erythematosus or Sjogren`s syndrome are allowed to enter the study at the Investigator`s discretion. 2. Patients who have been treated with: a. Igs and/or monoclonal antibodies within 6 months prior to randomization; b. rituximab, cyclophosphamide, or other immunosuppressive treatments with effects potentially lasting over 6 months, within 12 months prior to randomization; c. a medium or high dose corticosteroid therapy in the last 8 weeks prior to randomization; d. antimalarial agents in the last 6 weeks prior to randomization; e. biologic therapies, such as etanercept, within the last 4 weeks prior to randomization; f. any other immunosuppressive or immunomodulatory therapy such as methotrexate, azathioprine, cyclosporin A or mycophenolate, thalidomide, retinoids or dapsone in the last 4 weeks prior to randomization; g. total lymphoid irradiation or bone marrow transplantation. 3. Pregnant, planning to get pregnant, and/or lactating females or males planning to father a child within time period of the study or subsequent exclusionary period. 4. Participation in any clinical investigation within 4 weeks prior to screening or longer if required by local regulations. 5. Diagnosis or history of macular edema. 6. Any of the following cardiovascular conditions: a. history or presence of stable or unstable ischemic heart disease (IHD), myocardial infarction, myocarditis, or cardiomyopathy; b. history of angina pectoris due to coronary spasm; c. cardiac failure at time of Screening (Class II - IV, according to NYHA Classification) or any severe cardiac disease as determined by the investigator; d. history of cardiac arrest; e. history of symptomatic bradycardia; f. resting pulse rate <55 bpm prior to randomization; g. history or presence of a clinically relevant impairment of cardiac conduction including sick sinus syndrome, or sino-atrial heart block, clinically significant AV block, bundle branch block or QTc > 450 msec for males and > 470 msec for females at Screening or Baseline ECG; h. history or presence of symptomatic arrhythmia or arrhythmia requiring treatment; i. arterial hypertension uncontrolled by medication, if controlled the medication must be stable for three (3) months prior to baseline visit; j. treatment with medication that impairs cardiac conduction; k. treatment with quinidine; l. history of syncopes of suspected cardiac origin. 7. Any of the following pulmonary conditions: a. pulmonary fibrosis or any severe respiratory disease or significant bronchoconstrictive disease; b. tuberculosis, except for history of successfully treated tuberculosis or history of prophylactic treatment after positive PPD skin reaction; c. patients receiving chronic (daily) therapies for asthma. 8. History of clinically significant drug allergy. 9. History or presence of malignancy (except for successfully treated basal or squamous cell carcinoma of skin). 10. Uncontrolled diabetes mellitus or diabetes complicated with organ involvement such as diabetic nephropathy or retinopathy. 11. Active systemic bacterial, viral or fungal infections, or diagnosis of AIDS, Hepatitis B, Hepatitis C infection defined as a positive HIV antibody, Hepatitis B

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

Health Condition(s) or Problem(s) studied

active subacute cutaneous lupus erythematosus
MedDRA version: 9.1 Level: HLT Classification code 10025135

Intervention(s)

Pharmaceutical Form: Capsule, hard
CAS Number: 509088-69-1
Current Sponsor code: KRP203A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: .1-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Code: KRP203A
Pharmaceutical Form: Capsule, hard
CAS Number: 509088-69-1
Current Sponsor code: KRP203A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: .4-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Code: KRP203A
Pharmaceutical Form: Capsule, hard
CAS Number: 509088-69-1
Current Sponsor code: KRP203A
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To assess the safety and tolerability of oral KRP203 in patients with subacute cutaneous lupus erythematosus. To assess steady-state blood concentrations of KRP203 and KRP203-P in SCLE patients. To assess changes in the activity of SCLE using visual analogue scales for global skin health as assessed by the physician and the patient. To assess the systemic features of SCLE using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).

Main Objective: To assess the preliminary clinical efficacy of oral KRP203 in clinically active, treatment refractory patients with subacute cutaneous lupus erythematosus (SCLE) after 12 weeks of treatment with KPR203 as compared to placebo. Efficacy will be assessed by using the activity score of the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI).

Primary end point(s): Mean difference from baseline in the activity score of CLASI (from now on referred to only as CLASI)

Secondary ID(s)

2010-019689-10-DE

CKRP203A2202