Atacicept Phase II/III in Generalized Systemic Lupus Erythematosus (APRIL SLE)

• Register: EUCTR
• Last refreshed on: 25 November 2019
• Main ID: EUCTR2007-003698-13-GB
• Date of registration: 13/12/2007
• Prospective Registration: Yes
• Primary sponsor: Merck Serono S.A. Geneva. An affiliate of Merck KGaA, Darmstadt, Germany
• Public title: Atacicept Phase II/III in Generalized Systemic Lupus Erythematosus (APRIL SLE)
• Scientific title: A randomised, double-blind, placebo-controlled, multicentre prospective dose-finding Phase II/III study with atacicept given subcutaneously to subjects having recently experienced a flare of systemic lupus erythematosus (SLE) - Atacicept in generalised SLE Phase II/III
• Date of first enrolment: 06/03/2008
• Target sample size: 510
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-003698-13
• 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: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Brazil, Bulgaria, Chile, Croatia, Czech Republic, France, Germany, Greece, India, Israel, Korea, Republic of, Latvia, Lebanon, Lithuania, Malaysia, Mexico, Netherlands, Peru, Philippines, Serbia, Spain, Switzerland, Taiwan, United Kingdom, United States

Contacts

• Name: Communication center Merck KGaA
• Affiliation: Merck Serono S.A. Geneva. An affiliate of Merck KGaA, Darmstadt, Germany

• Name: Communication center Merck KGaA
• Affiliation: Merck Serono S.A. Geneva. An affiliate of Merck KGaA, Darmstadt, Germany

Key inclusion & exclusion criteria

Inclusion criteria:
1. Diagnosis of SLE satisfying at least 4 out of the 11 ACR criteria at the time of diagnosis, with a disease duration of at least six months.
2. Active SLE with at least one BILAG A or B score at initial screening (excluding a single B due to haematological values) requiring a change in the dose of corticosteroids.
3. Positive antinuclear antibody (ANA) test results (HEp-2 ANA =1:80 and/or anti dsDNA =30 IU/mL) (subjects will be tested at screening).
4. Male or female =16 years of age.
5. Written informed consent, given before any study-related procedure. Subjects must have read and understood the Informed Consent Form, must fully understand the requirements of the study and must be willing to comply with all study visits and assessments. For subjects under the age of legal majority (according to local law), the subject and a legal guardian must read and sign the informed consent.
6. Female subjects must be willing to avoid pregnancy by using an adequate method of contraception for 4 weeks prior to Study Day 1, during the trial and 24 weeks after the last dose of study medication. This requirement does not apply to surgically sterile subjects or to subjects who are post-menopausal for at least 2 years. Adequate contraception is defined as two barrier methods, or one barrier method with a spermicide, or an intrauterine device or use of a female hormonal contraceptive.
7. Women of childbearing potential must have a negative serum pregnancy test at initial screening and at the end of screening before dosing. For the purpose of this study, women of childbearing potential are defined as all female subjects after puberty unless they are post-menopausal for at least 2 years or surgically sterile.

In addition, to be eligible for inclusion into this trial, subjects must fulfil the following criteria at the end of the initial flare treatment period:
8. Improvement of the qualifying BILAG A or B flare to BILAG C or D within 10 weeks after commencing steroid treatment.
9. Use of an appropriate steroid regimen for the qualifying flare during the screening period, with stability of the dose at 7.5 mg of prednisone or equivalent for 2 weeks after improvement to BILAG C or D.
10. No other new BILAG A or B at an assessment performed following confirmation of stable steroid dose.

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) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Any condition, including laboratory findings and findings in the medical history or in the pre-study assessments, that constitutes a risk or a contraindication for participation to the study in the opinion of the Investigator or that could interfere with study objectives, conduct or evaluation.
2. Active moderate to severe glomerulonephritis
3. Active central nervous system SLE deemed to be severe or progressive and/or associated with significant cognitive impairment leading to inability to provide informed consent and/or comply with the protocol.
4. Comorbidities requiring systemic corticosteroid therapy (such as asthma or inflammatory bowel disease) and/or preventing engagement in study conduct.
5. Any history of treatment with rituximab, abatacept or belimumab.
6. Introduction of azathioprine, hydroxychloroquine, chloroquine, or methotrexate within 2 months before initial screening or increase in the dose regimen of any of these medications within 2 months before initial screening.
7. Initiation of any immunosuppressive drug within 3 months before initial screening.
8. Participation in any interventional clinical trial within the last 28 days or within 5 half-lives of the investigated compound (whichever is longer) before initial screening.
9. Treatment with cyclophosphamide mycophenolate mofetil or a calcineurin inhibitor within 3 months before initial screening.
10. Treatment with leflunomide, 6-mercaptopurine or thalidomide within 3 months before initial screening.
11. Active infection with herpes zoster or Epstein-Barr virus at initial screening.
12. Positive HIV serology (subjects will be tested at screening).
13. Positive hepatitis B surface antigen (HBsAg) or hepatitis C serology (subjects will be tested at screening).
14. History or presence of tuberculosis infection without documentation of adequate treatment, or treatment that occurred in the past year. Subjects should be evaluated and screened for tuberculosis according to national or local recommendations.
15. Known active clinically significant acute or chronic infection, or any major episode of infection requiring hospitalisation or treatment with parenteral anti-infectives within 4 weeks of baseline or completion of oral anti-infectives within 2 weeks prior to screening.
16. Diagnosis or family history of Creutzfeldt-Jakob disease (CJD).
17. History or presence of uncontrolled or New York Heart Association (NYHA) class 3 or 4 congestive heart failure.
18. History of cancer, except for adequately treated basal cell carcinoma of the skin, cervical dysplasia or carcinoma in situ of the skin or the cervix.
19. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase (AP) level > 2.5 x ULN, or total bilirubin > 1.5 x ULN.
20. Clinically significant abnormality in any haematological test (e.g. haemoglobin < 5.5 mmol/L, WBC < 2.5 x 10^9/L, platelets < 75 x 10^9/L) unless attributable to active SLE.
21. Serum immunoglobulin G below 6 g/L.
22. Clinically significant abnormality on chest X-ray performed within 3 months of initial screening or on ECGs performed at initial screen

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

Health Condition(s) or Problem(s) studied

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

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

Intervention(s)

Product Name: Atacicept
Product Code: TACI-Fc5
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Atacicept
CAS Number: 845264-92-8
Other descriptive name: TACI-Fc5
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: range
Concentration number: 75-150
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: From Study Day (SD) 1 until Week 52 or early termination.

Secondary Objective: Secondary objectives of the trial are:
- To evaluate the safety and tolerability profile of atacicept in treated subjects with SLE,
- To confirm the optimal dose of atacicept for treatment of subjects with SLE,
- To gain further information on the effect of atacicept on relevant markers specific to its mechanism of action (MoA) and their correlation to disease activity/progression,
- To further characterise the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of atacicept, and
- To identify genetic and genomic variations associated with drug response and disease activity/progression.

Main Objective: The primary objective of this trial is to evaluate the efficacy of atacicept compared to placebo in preventing new flares in subjects with SLE.

Primary end point(s): The primary efficacy endpoint of this trial is the proportion of subjects experiencing a new flare (as defined by a British Isles Lupus Assessment Group [BILAG] score of A or B) during the 52-week treatment period following randomisation.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1. Randomisation to week 52 or early termination
2. Week 52
3. Randomisation to Week 24
4. Randomisation to Week 52

Secondary end point(s): 1. Time to new flare from randomization (main secondary endpoint)
2. Proportions of subjects within each of the following ordinal response categories at Week 52; No flare, first new flare scored as BILAG B and first new flare scored as BILAG A.
3. Proportion of subjects with a new flare (BILAG A or B) within the initial 24 weeks after randomisation.
4. Corticosteroid exposure post-randomisation

Secondary ID(s)

27646

Source(s) of Monetary Support

Merck Serono S.A. Geneva.

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 25/06/2016
• Date Completed: 31/10/2010
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-003698-13/results