Clinical trial NCT03504852: Efficacy and Safety of 2 Secukinumab Regimens in 90kg or More Weight Group With Moderate/Severe Chronic Plaque Psoriasis
Official title: A Randomized, Double-blind, Multicenter Study Assessing Short and Long-term Efficacy, Safety, and Tolerability of Sub-cutaneous Secukinumab in Subjects of Body Weight 90 kg or Higher With Moderate to Severe Chronic Plaque-type Psoriasis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Moderate to Severe Chronic Plaque-type Psoriasis
Keywords: psoriasis
secukinumab
immune-mediated systemic disease
papules
plaques
itching
weight
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2018-04-20
Enrollment: 331
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The purpose of this study is to assess secukinumab high dose (every 2 weeks) vs standard dose (every 4 weeks) in heavy body weight subjects with moderate to severe plaque psoriasis.

Detailed description: A 52-week multicenter, randomized, double-blind, parallel-group trial in 331 subjects with moderate to severe chronic plaque-type psoriasis of body weight 90 kg or higher at time of randomization.

This study consisted of 4 periods: screening (up to 4 weeks), treatment Period 1 (16 weeks), treatment Period 2 (36 weeks), and post-treatment follow-up (8 weeks).

Subjects were randomized using a 1:1 ratio to the following groups: Secukinumab 300 mg every 2 weeks; Secukinumab 300 mg every 4 weeks.

In addition, subjects from the 300 mg every 4 weeks group who did not achieve Psoriasis Area Severity Index (PASI) 90 response at Week 16 were reassigned using a 1:1 ratio to either remain on secukinumab 300 mg every 4 weeks or receive secukinumab 300 mg every 2 weeks starting at Week 16, until the end of treatment.

Eligibility criteria: Key Inclusion Criteria:

* Written informed consent must have been obtained before any assessment was performed. Where relevant, a legal representative will also have signed the informed study consent according to local laws and regulations.
* Subjects must have been able to understand and communicate with the investigator and comply with the requirements of the study.
* Men or women at least 18 years of age at time of screening.
* Body weight of ≥ 90 kg at the time of randomization.
* Chronic plaque-type psoriasis present for at least 6 months and diagnosed before randomization.
* Moderate to severe psoriasis as defined at randomization by:

  * Psoriasis Area and Severity Index (PASI) score of 12 or greater, and
  * Investigator's Global Assessment (IGA) mod 2011 score of 3 or greater (based on a static scale of 0 - 4), and
  * Body Surface Area (BSA) affected by plaque-type psoriasis of 10% or greater.
* Candidate for systemic therapy. This is defined as a subject having moderate to severe chronic plaque-type psoriasis that is inadequately controlled by:

  * topical treatment and/or,
  * phototherapy and/or,
  * previous systemic therapy.

Key Exclusion Criteria:

* Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and guttate psoriasis) at screening or Randomization.
* Ongoing use of prohibited treatments. Washout periods detailed in the protocol have to be adhered to. Subjects not willing to limit ultraviolet (UV) light exposure (e.g., sunbathing and / or the use of tanning devices) during the course of the study will be considered not eligible for this study since UV light exposure is prohibited. Note: administration of live vaccines 6 weeks prior to Randomization or during the study period is also prohibited.
* Previous exposure to secukinumab (AIN457) or any other biologic drug directly targeting Interleukin-17 (IL-17) or the IL-17 receptor.
* Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 4 weeks until the expected pharmacodynamic effect has returned to baseline, whichever is longer; or longer if required by local regulations.
* Pregnant or nursing (lactating) women
* History of lymphoproliferative disease or any known malignancy or history of malignancy of any organ system treated or untreated within the past 5 years, regardless of whether there is evidence of local recurrence or metastases (except for skin Bowen's disease, or basal cell carcinoma or actinic keratoses that have been treated with no evidence of recurrence in the past 12 weeks; carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been removed).
* History of hypersensitivity to any of the study drug constituents.

Primary outcomes:
measure: Percentage of Subjects Who Achieve 90% or Greater Reduction in Psoriasis Area and Severity Index (PASI) Score - Week 16 (Full Analysis Set)
timeFrame: 16 weeks
Secondary outcomes:
measure: Percentage of Subjects Who Achieve Investigator Global Assessment (IGA Modified 2011) Score of 0 or 1 - Week 16 (Full Analysis Set)
timeFrame: 16 weeks
measure: Absolute and Relative Frequencies for Deaths, Other Serious or Clinically Significant Adverse Events or Related Discontinuations - Entire Study Period (Safety Set)
timeFrame: Adverse events were reported from first dose of study treatment until end of study treatment plus 8 weeks post treatment, up to a maximum timeframe of 470 days.
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novartis Investigative Site
state: Alabama
city: Phoenix
country: United States
facility: Novartis Investigative Site
state: Arizona
city: Rogers
country: United States
facility: Novartis Investigative Site
state: Arkansas
city: Irvine
country: United States
facility: Novartis Investigative Site
state: California
city: Sacramento
country: United States
facility: Novartis Investigative Site
state: California
city: Sacramento
country: United States
facility: Novartis Investigative Site
state: California
city: San Diego
country: United States
facility: Novartis Investigative Site
state: California
city: Santa Monica
country: United States
facility: Novartis Investigative Site
state: California
city: Centennial
country: United States
facility: Novartis Investigative Site
state: Colorado
city: Tampa
country: United States
facility: Novartis Investigative Site
state: Florida
city: West Palm Beach
country: United States
facility: Novartis Investigative Site
state: Florida
city: Alpharetta
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Snellville
country: United States
facility: Novartis Investigative Site
state: Georgia
city: Skokie
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Indianapolis
country: United States
facility: Novartis Investigative Site
state: Indiana
city: New Albany
country: United States
facility: Novartis Investigative Site
state: Indiana
city: Louisville
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Owensboro
country: United States
facility: Novartis Investigative Site
state: Kentucky
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: New Brighton
country: United States
facility: Novartis Investigative Site
state: Minnesota
city: Saint Joseph
country: United States
facility: Novartis Investigative Site
state: Missouri
city: East Windsor
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Verona
country: United States
facility: Novartis Investigative Site
state: New Jersey
city: Forest Hills
country: United States
facility: Novartis Investigative Site
state: New York
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Charlotte
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Novartis Investigative Site
state: North Carolina
city: Fairborn
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Oregon City
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Portland
country: United States
facility: Novartis Investigative Site
state: Oregon
city: Charleston
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Houston
country: United States
facility: Novartis Investigative Site
state: Texas
city: Mesquite
country: United States
facility: Novartis Investigative Site
state: Texas
city: Pflugerville
country: United States
facility: Novartis Investigative Site
state: Texas
city: San Antonio
country: United States
facility: Novartis Investigative Site
state: Texas
city: Norfolk
country: United States
facility: Novartis Investigative Site
state: Virginia
city: Wenatchee
country: United States
facility: Novartis Investigative Site
state: Washington
city: Madison
country: United States
facility: Novartis Investigative Site
state: Wisconsin
city: Calgary
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Red Deer
country: Canada
facility: Novartis Investigative Site
state: Alberta
city: Etobicoke
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Guelph
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Prague
country: Czechia
facility: Novartis Investigative Site
state: Prague 1
city: Novy Jicin
country: Czechia
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Kiel
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Pecs
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Modena
country: Italy
facility: Novartis Investigative Site
state: MO
city: Perugia
country: Italy
facility: Novartis Investigative Site
state: PG
city: Siena
country: Italy
facility: Novartis Investigative Site
state: SI
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Chelyabinsk
country: Russian Federation
facility: Novartis Investigative Site
city: Ekaterinburg
country: Russian Federation
facility: Novartis Investigative Site
city: Kazan
country: Russian Federation
facility: Novartis Investigative Site
city: Krasnodar
country: Russian Federation
facility: Novartis Investigative Site
city: Lipetsk
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Saratov
country: Russian Federation
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Augustin M, Reich K, Yamauchi P, Pinter A, Bagel J, Dahale S, You R, Bruin G, Djimopoulos J, Paguet B, Charef P, Patekar M, Keefe D. Secukinumab dosing every 2 weeks demonstrated superior efficacy compared with dosing every 4 weeks in patients with psoriasis weighing 90 kg or more: results of a randomized controlled trial. Br J Dermatol. 2022 Jun;186(6):942-954. doi: 10.1111/bjd.20971. Epub 2022 Apr 8.