E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Lupus Erythematosus |
Aktywny toczeń trzewny |
|
E.1.1.1 | Medical condition in easily understood language |
Lupus |
Aktywny toczeń trzewny |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10042945 |
E.1.2 | Term | Systemic lupus erythematosus |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of ustekinumab as measured by a reduction in disease activity for subjects with active SLE |
Celem głównym badania jest ocena skuteczności ustekinumabu mierzonej stopniem zmniejszenia aktywności choroby u pacjentów z aktywnym toczniem rumieniowatym układowym (SLE). |
|
E.2.2 | Secondary objectives of the trial |
To evaluate:
• The safety and tolerability of ustekinumab in subjects with SLE.
• The effect of ustekinumab administration on health-related quality of life in subjects with SLE.
• The effects of ustekinumab on cutaneous manifestations of SLE.
• Pharmacokinetics and immunogenicity of ustekinumab in subjects with SLE |
Cele drugorzędowe badania, to ocena:
• Bezpieczeństwa i tolerancji ustekinumabu u pacjentów z SLE.
• Wpływu podawania ustekinumabu na związaną ze stanem zdrowia jakość życia u pacjentów z SLE.
• Oddziaływania ustekinumabu na objawy skórne SLE.
• Farmakokinetyki oraz immunogenności ustekinumabu u pacjentów z SLE.
|
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Protocol A0 - dated 19 December 2014 - Subjects who provide consent will be enrolled in the cutaneous lupus substudy evaluating the histology of cutaneous biopsies and/or skin photographs. Subjects participating in the cutaneous lupus substudy are not required to undergo biopsies, and may allow only photographs to document changes in an identified lesion or area of active disease |
Pacjenci z toczniem skórnym, którzy wyrażą na to zgodę, zostaną włączeni do udziału w podbadaniu dotyczącym tocznia skórnego obejmującym ocenę histologiczną bioptatów skóry oraz/lub fotografii skóry. Od pacjentów, którzy wyrazili na to zgodę bioptaty zostaną pobrane z pojedynczej zmiany patologicznej lub obszaru czynnej choroby skórnej. Od pacjentów uczestniczących w podbadaniu dotyczącym tocznia skórnego nie będzie wymagane poddanie się biopsjom i będą oni mogli wyrazić zgodę także wyłącznie na wykonanie fotografii w celu udokumentowania zmian określonej zmiany patologicznej lub obszaru czynnej choroby. Pacjenci z toczniowymi zmianami skórnymi nie nadającymi się do oceny za pomocą biopsji (np. wysypka w kształcie motyla lub łysienie) również mogą być włączani do podbadania i mogą podlegać ocenie z zastosowaniem fotografii. |
|
E.3 | Principal inclusion criteria |
1. Subjects must have documented medical history to meet SLICC classification criteria for SLE for a minimum of 3 months prior to first dose
2. At least 1 welldocumented (subject file, referring physician letter, or laboratory result), unequivocally positive, documented test for autoantibodies in medical history including either of the following: ANA, and/or antidsDNA antibodies, and/or antiSmith
antibodies
- At least 1 unequivocally positive autoantibody test including ANA and/or antidsDNA antibodies and/or antiSmith antibodies detected during screening
- At least 1 BILAG A and/or 2 BILAG B domain scores observed during screening prior to first administration of study agent Demonstrate active disease based on SLEDAI2K score greater than or
equal to (>=) 6 observed during screening and assessed approximately 2 to 6 weeks prior to randomization. Must also have SLEDAI2K score >= 4 for clinical features (ie, SLEDAI excluding laboratory results) at Week 0 prior to the first administration of study agent
3. Subjects must not have permanently discontinued study treatment on
or before their Week 40 visit and are able to either continue q8w SC
dosing at approximately 8 weeks (±2 weeks) beyond their Week 40 visit,
or are able to resume dosing at Week 56 with no more than 16 weeks
(±2 weeks) since their Week 40 visit.
4. In the judgment of the study investigator, the potential benefit of
continuing ustekinumab long-term treatment outweighs the risks for the
subject.
5.Each subject must sign a revised informed consent indicating
agreement to participate in the extended study |
|
E.4 | Principal exclusion criteria |
- Have other inflammatory diseases that might confound the evaluations of efficacy, including but not limited to rheumatoid arthritis (RA), psoriatic arthritis (PsA), RA/lupus overlap, psoriasis or active Lyme disease
- Are pregnant, nursing, or planning a pregnancy or fathering a child while enrolled in the study or within 4 months after receiving the last administration of study agent
- Have received systemic or topical cream/ointment preparations of cyclosporine A or other systemic immunomodulatory agents other than those described in inclusion criteria within the past 3 months prior to first administration of study agent
- Have received a single B cell targeting agent within 3 months prior to first study agent administration; or received more than 1 previous B cell targeting therapy including belimumab or epratuzamab within 6 months prior to first administration of the study agent; or received B cell depleting therapy (eg, rituximab) within 12 months prior to first administration of the study agent or have evidence of continued Bcell depletion following such therapy
- Have ever received ustekinumab
- Participant has a history of malignancy within 5 years before screening
- Have received prior immunomodulatory biologic therapy for lupus not
described in Exclusion Criterion #4 including, but not limited to,
tocilizumab, alefacept, efalizumab, natalizumab, abatacept, anakinra,
brodalumab, secukinumab, ixekizumab, inhibitors of TNF, IL-1, IL-6, IL-
17, or interferon pathways, less than 5 half-lives or 3 months, whichever
is longer, prior to first administration of the study agent.
- Have received, or are expected to receive, any live virus or bacterial
vaccination within 3 months before the first administration of study
agent, during the study, or within 3 months after the last administration
of study agent
- Has received an investigational drug that is not previously defined in
other exclusion criteria within 5 half-lives or 3 months, whichever is
longer, or used an invasive investigational medical device within 3
months before the planned first dose of study drug, or is currently
enrolled in an interventional study.
- Subject is an employee of the investigator or study site, with direct
involvement in the proposed study or other studies under the direction
of that investigator or study site, as well as family members of the
employees or the investigator.
- Lives in an institution on court or authority order, unless permitted
by local regulations. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of Participants With a Composite SRI-4 Response at Week 24 |
porównanie odsetka pacjentów ze złożoną odpowiedzią ocenianą według wskaźnika SRI-4 w tygodniu 24 u pacjentów przyjmujących ustekinumab w porównaniu z pacjentami otrzymującymi placebo. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Change From Baseline in SLEDAI-2K Score at Week 24.
- Change From Baseline in Physician Global Assessment of Disease Activity (PGA) at Week 24
- Percentage of Participants With BICLA Response at Week 24 |
• Zmiana od punktu wyjściowego wskaźnika SLEDAI-2K w tyg 24
• Zmiana od punktu wyjściowego Oceny globalnejaktywności choroby przez lekarza (ang. Physician’s Global Assessment of Disease Activity) w tyg 24
• Odsetek uczestników z odpowiedzią BICLA w tygodniu 24
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Germany |
Hungary |
Mexico |
Poland |
Spain |
Taiwan |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
LSLV |
ostatnia wizyta ostatniego uczestnika |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 25 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 13 |