This study will assess if a more prolonged dose interval (every 6 weeks compared to every 4 weeks) will allow psoriasis patients who achieveclear or almost clear skin after 24 weeks of secukinumab treatment - Psoriasis Area and Severity Index (PASI…
ID
Source
Brief title
Condition
- Skin and subcutaneous tissue disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective is to demonstrate in the patient pool of PASI 90
responders at Week 24 that secukinumab 300 mg s.c. every 6 weeks
treatment is non-inferior to secukinumab 300 mg s.c. every 4 weeks treatment
with respect to maintaining a PASI 90 response rate at
Week 52.
Secondary outcome
The key secondary objective is to demonstrate in the patient pool of PASI 75
responders who do not reach a PASI 90 response at Week 24
that secukinumab 300 mg s.c. administered every 2 weeks is superior to
secukinumab 300 mg s.c. administered every 4 weeks at Week 52 based
on the PASI 90 response rate.
Background summary
Reducing maintenance dosing regimens for patients treated with (biologic) drugs
offers benefits, such as minimizing patients* exposure to
the drug substance while keeping an acceptable clinical response. In contrast,
patients not responding adequately to a drug substance can
benefit from an increased frequency of drug dosing. In daily clinical practice,
a change of the dose frequency for marketed substances can be
assumed to happen often depending on the treatment response of patients. A
secukinumab dose of 300 mg s.c. every 4 weeks as a
maintenance treatment dose regimen has been evaluated extensively in a Phase 3
clinical trial program and shown strong sustainability of
treatment response over 52 weeks
Study objective
This study will assess if a more prolonged dose interval (every 6 weeks
compared to every 4 weeks) will allow psoriasis patients who achieve
clear or almost clear skin after 24 weeks of secukinumab treatment - Psoriasis
Area and Severity Index (PASI) * 90 - to maintain this skin
response for a further 28 weeks (52 weeks in total). The study will also assess
if a dose interval (dosing every 2 weeks compared to every
4 weeks) will allow psoriasis patients who fail to achieve a PASI 90 response
after 24 weeks of secukinumab treatment to meet the PASI 90
response target in a further 28-week study period.
Study design
This is a randomized, open-label, assessment-blinded, multicenter, 52-week
study to evaluate the efficacy (based on PASI 90), safety and
tolerability of secukinumab 300 mg s.c. in patients with moderate to severe
chronic plaque psoriasis. This study consists of 2 treatment
periods: a 24-week run-in treatment period (Baseline to Week 24) and a 28-week
maintenance treatment period (Week 24 to Week 52).
For Treatment Period 1 (Baseline to Week 24) all patients will receive the same
treatment: 300 mg of secukinumab by s.c. injection with initial
dosing at Weeks 0, 1, 2, and 3 followed by dosing every 4 weeks.
For Treatment Period 2 (Week 24 to Week 52) patients will be randomly assigned
to one of 4 treatment groups depending on their PASI response
to treatment.
Patients with PASI 90 (psoriasis clear or almost clear skin) will be randomized
at Week 24 on a 1:1 basis to Group 1 or Group 2:
* Group 1 (recommended maintenance treatment): secukinumab 300 mg s.c. every 4
weeks.
* Group 2 (experimental dosing maintenance treatment): secukinumab 300 mg s.c.
every 6 weeks.
Patients who do not achieve a PASI 90 response at Week 24 but achieve at least
a PASI 75 response will be eligible for dose frequency
intensification and will be randomized on a 1:1 basis to either Group 3 or
Group 4:
* Group 3 (recommended maintenance treatment): secukinumab s.c. 300 mg every 4
weeks.
* Group 4 (experimental maintenance treatment): secukinumab s.c. 300 mg every 2
weeks.
Patients from Group 3 and Group 4 will enter a treatment-free follow-up period
from Week 52 until Week 60.
Patients without a PASI 75 response at Week 24 will not be eligible for
randomization and will be discontinued from the study.
Randomization will be stratified by body weight collected at the Randomization
Visit (< 90 kg or * 90 kg).
Intervention
Patients with PASI 90 (psoriasis clear or almost clear skin) will be randomized
at Week 24 on a 1:1 basis to Group 1 or Group 2:
* Group 1 (recommended maintenance treatment): secukinumab 300 mg s.c. every 4
weeks.
* Group 2 (experimental dosing maintenance treatment): secukinumab 300 mg s.c.
every 6 weeks.
Patients who do not achieve a PASI 90 response at Week 24 but achieve at least
a PASI 75 response will be eligible for dose frequency
intensification and will be randomized on a 1:1 basis to either Group 3 or
Group 4:
* Group 3 (recommended maintenance treatment): secukinumab s.c. 300 mg every 4
weeks.
* Group 4 (experimental maintenance treatment): secukinumab s.c. 300 mg every 2
weeks.
Study burden and risks
Burden:
More clinic visits that also take more time than routine visits.
Administration of 2 sub-cutaneous injections: 14, 16 or 22x. # is dependent on
treatment group (1-4).
Physical examination, assessment severity psoriasis inclusive: Each visit;
18-19x. Inclusive assessment length 1x, weight 4-5x, bloodpressure and pulse
10-11x. # is dependent on treatment group (1-4).
ECG: 4x.
Blood collection (9-26ml per collection) + urine collection:10-11x. # is
dependent on treatment group (1-4).
Female subjects: Pregancy test: 8-9x. 1x in serum and 7-8x in urine. Completion
of questionnaires (7 x max 20 minuten).# is dependent on treatment group (1-4).
Chest X-Ray in case this or CT- or MRI-Scan not performed within 3 months
before screening and assessment is available.
Risks:
Possible risks are adverse events of secukinumab and burden/risks of study
procedures.
Raapopseweg 1
Arnhem 6824 DP
NL
Raapopseweg 1
Arnhem 6824 DP
NL
Listed location countries
Age
Inclusion criteria
1. Men or women * 18.
2. Chronic plaque-type psoriasis diagnosed for at least 6 months prior to Screening and candidate for systemic therapy.
3. Moderate to severe psoriasis at Baseline as evidenced by:
* PASI * 10 and
* IGA mod 2011 score of 3 or higher (based on a scale of 0 to 4) and
* BSA affected by plaque-type psoriasis of * 10%.
Exclusion criteria
1. History of exposure to any biologic drug taken for the treatment of chronic plaque psoriasis or any other indication including but not limited to anti-tumor necrosis factor (TNF) alpha, anti-interleukin (IL)12/23, or any anti-IL-17A or IL-17A receptor (IL 17AR) antibody.
2. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes including latex hypersensitivity.
3. Forms of psoriasis other than chronic plaque-type (eg, pustular, erythrodermic and guttate psoriasis).
4. Drug-induced psoriasis (ie, new onset or current exacerbation from beta-blockers, calcium channel inhibitors or lithium).
5. Ongoing use of prohibited psoriasis treatments (eg, topical or systemic corticosteroids, ultraviolet (UV) therapy).
6. Ongoing use of other non-psoriasis prohibited treatments. Washout periods detailed in the protocol have to be adhered to. All other prior non-psoriasis concomitant treatments must be at a stable dose as detailed in the protocol before initiation of study drug.
7. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL).
8. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during entire study or longer if
required by locally approved prescribing information (e.g. in EU 20 weeks).
9. Active ongoing inflammatory diseases other than psoriasis that might confound the evaluation of the benefit of secukinumab therapy.
10. Underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions) which, in the opinion of the Investigator, significantly immunocompromises the patient and/or places the patient at unacceptable risk for receiving an immunomodulatory therapy.;See protocol for other exclusion criteria.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-005339-15-NL |
| ClinicalTrials.gov | NCT02409667 |
| CCMO | NL52659.060.15 |