Clinical trial NCT03701763: Efficacy and Safety Study of Apremilast (CC-10004) in Pediatric Subjects From 6 Through 17 Years of Age With Moderate to Severe Plaque Psoriasis
Official title: A PHASE 3, MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO ASSESS THE EFFICACY AND SAFETY OF APREMILAST (CC-10004) IN PEDIATRIC SUBJECTS FROM 6 THROUGH 17 YEARS WITH MODERATE TO SEVERE PLAQUE PSORIASIS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Psoriasis
Keywords: Pediatric
6 through 17 years
Plaque Psoriasis
Psoriasis
CC-10004
Apremilast
Otezla
Children
Adolescents
SPROUT
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2018-10-10
Enrollment: 245
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 3, multicenter, randomized, placebo-controlled, double-blind study of the efficacy and safety of apremilast (CC-10004) in pediatric subjects with moderate to severe plaque psoriasis.

At least 230 pediatric subjects (ages 6 through 17 years) will be randomized 2:1 to receive either apremilast or placebo for the first 16 weeks and then all subjects will receive apremilast during the 36 week Extension Phase for a total of 52 weeks. Randomization to apremilast arm or placebo arm will be stratified by age group (6 to 11 years or 12 to 17 years). Subjects will receive apremilast treatment of either 20 mg twice daily (BID) or 30 mg BID, depending on weight. This Phase 3 study is being conducted to evaluate the safety and efficacy of apremilast in the treatment of pediatric subjects.

Detailed description: Treatment will be assigned by weight with subjects 20 kg to \< 50 kg receiving apremilast 20 mg BID or placebo BID and subjects ≥ 50 kg receiving apremilast 30 mg BID or placebo BID. Total study duration is up to 71 weeks. Subjects completing all 52 weeks of the treatment and extension phase will be able to enter the Long-term study. Subjects not entering the Long-term study will return for 3 observational follow-up visits, 4, 8 and 14 weeks after last dose of study drug.

Eligibility criteria: Inclusion Criteria:

1. Males or female subjects 6 to 17 years of age, inclusive, at the time the informed consent form is signed by the legal guardian
2. Subjects must have a weight of ≥ 20 kg
3. Diagnosis of chronic plaque psoriasis for at least 6 months prior to Screening.
4. Has moderate to severe plaque psoriasis at Screening and Baseline as defined by:

   * PASI score ≥ 12; and
   * Body surface area (BSA) ≥ 10%; and
   * sPGA ≥ 3 (moderate to severe)
5. Disease inadequately controlled by or inappropriate for topical therapy for psoriasis
6. Candidate for systemic therapy or phototherapy

Exclusion Criteria:

1. Guttate, erythrodermic, or pustular psoriasis at Screening and Baseline
2. Psoriasis flare or rebound within 4 weeks prior to Screening
3. Prior history of suicide attempt at any time in the subject's lifetime prior to Screening or randomization in the study, or major psychiatric illness requiring hospitalization within 3 years prior to signing the assent and informed consent
4. Answer "Yes" to any question on the Columbia-Suicide Severity Rating Scale during Screening or at Baseline
5. Current or planned concurrent use of the following therapies that may have a possible effect on psoriasis

   a. Topical therapy within 2 weeks prior to randomization (including but not limited to topical corticosteroids, topical retinoid or vitamin D analog preparations, tacrolimus, pimecrolimus, or anthralin/dithranol)

   Exceptions\*:

   i. Low potency or weak corticosteroids (please refer to the Investigators' Manual) will be allowed as background therapy for treatment of the face, axillae and groin in accordance with manufacturer's suggested usage ii. Unmedicated skin moisturizer (eg, Eucerin®) will also be permitted for body lesions

   \*Subjects should not use these topical treatments within 24 hours prior to the clinic visit.

   b. Conventional systemic therapy for psoriasis within 4 weeks prior to randomization c. Phototherapy treatment (ie, ultraviolet B \[UVB\], PUVA) within 4 weeks prior to randomization d. Biologic therapy within 4 weeks prior to randomization or 5 PK/PD half-lives (whichever is longer).

Primary outcomes:
measure: Percentage of Participants With a Static Physician Global Assessment (sPGA) Response at Week 16
timeFrame: Baseline to Week 16
Secondary outcomes:
measure: Percentage of Participants Who Achieved At Least 75% Reduction in Psoriasis Area Severity Index (PASI-75) From Baseline at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants Who Achieved At Least 50% Reduction in Psoriasis Area Severity Index (PASI-50) From Baseline at Week 16
timeFrame: Baseline and Week 16
measure: Percentage Change From Baseline in Total PASI Score at Week 16
timeFrame: Baseline and Week 16
measure: Percentage Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants Who Achieved a Children's Dermatology Life Quality Index (CDLQI) Score of 0 or 1 at Week 16
timeFrame: Week 16
measure: Change From Baseline in CDLQI Score at Week 16
timeFrame: Baseline and Week 16
measure: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) During the Placebo-controlled Phase
timeFrame: 16 weeks
measure: Number of Participants Who Experienced a TEAE During the Apremilast Exposure Period
timeFrame: 52 weeks
measure: Number of Participants Who Experienced a Treatment-emergent Serious Adverse Event (TESAE) During the Placebo-controlled Phase
timeFrame: 16 weeks
measure: Number of Participants Who Experienced a TESAE During the Apremilast Exposure Period
timeFrame: 52 weeks
measure: Number of Participants Who Experienced a Treatment-related Adverse Event (TRAE) During the Placebo-controlled Phase
timeFrame: 16 weeks
measure: Number of Participants Who Experienced a TRAE During the Apremilast Exposure Period
timeFrame: 52 weeks
measure: Number of Participants With Diarrhea During the Placebo-controlled Phase
timeFrame: Up to approximately 113 days
measure: Number of Participants With Diarrhea During the Apremilast Exposure Period
timeFrame: Day 1 up to approximately 365 days
measure: Number of Participants With Diarrhea Symptoms During the Placebo-controlled Phase
timeFrame: Up to approximately 113 days
measure: Number of Participants With Diarrhea Symptoms During the Apremilast Exposure Period
timeFrame: Day 1 up to approximately 365 days
measure: Number of Participants With Suicidal Ideation or Behavior Per the Columbia-Suicide Severity Rating Scale (C-SSRS) During the Placebo-controlled Phase
timeFrame: 16 weeks
measure: Number of Participants With Suicidal Ideation or Behavior Per the C-SSRS During the Apremilast-extension Phase
timeFrame: Week 16 to Week 52
measure: Number of Female Participants at Stage I-V of Sexual Development Per Tanner Staging of Sexual Development
timeFrame: Week 52
measure: Number of Male Participants at Stage I-V of Sexual Development Per Tanner Staging of Sexual Development
timeFrame: Week 52
measure: Mean Body Weight of Participants During the Placebo-controlled Phase
timeFrame: Baseline and Week 16
measure: Mean Body Weight of Participants During the Apremilast Exposure Period
timeFrame: Baseline and Week 52
measure: Mean Height of Participants During the Placebo-controlled Phase
timeFrame: Baseline and Week 16
measure: Mean Height of Participants During the Apremilast Exposure Period
timeFrame: Baseline and Week 52
measure: Mean Body Mass Index (BMI) of Participants During the Placebo-controlled Phase
timeFrame: Baseline and Week 16
measure: Mean BMI of Participants During the Apremilast Exposure Period
timeFrame: Baseline and Week 52
measure: Number of Participants Who Experienced a Psoriasis Flare During the Placebo-controlled Phase
timeFrame: 16 weeks
measure: Number of Participants Who Experienced a Psoriasis Flare During the Apremilast Exposure Period
timeFrame: 52 weeks
measure: Number of Participants Who Experienced a Psoriasis Rebound
timeFrame: 14 weeks post last dose (max mean treatment duration in placebo-controlled phase was 15.3 weeks, and 41.9 weeks in the apremilast-exposure period)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Childrens Hospital
state: Arizona
city: Fort Smith
country: United States
facility: Johnson Dermatology Clinic
state: Arkansas
city: Beverly Hills
country: United States
facility: Zenith Research Inc.
state: California
city: Fountain Valley
country: United States
facility: First OC Dermatology
state: California
city: Laguna Niguel
country: United States
facility: Avance Clinical Trials
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: San Luis Obispo
country: United States
facility: Coastal Family Dermatology
state: California
city: Santa Monica
country: United States
facility: University of California Los Angeles
state: California
city: Thousand Oaks
country: United States
facility: California Dermatology Institute
state: California
city: Jacksonville
country: United States
facility: Solutions Through Advanced Research Inc
state: Florida
city: Margate
country: United States
facility: Glick Skin Institute Clinical Research
state: Florida
city: Miami
country: United States
facility: University of Miami Hospital
state: Florida
city: Miami
country: United States
facility: Ciocca Dermatology
state: Florida
city: Tampa
country: United States
facility: University of South Florida Health Morsani Center for Advanced Healthcare
state: Florida
city: Macon
country: United States
facility: Skin Care Physicians of Georgia
state: Georgia
city: Meridian
country: United States
facility: Treasure Valley Medical Research
state: Idaho
city: Chicago
country: United States
facility: DeNova Research
state: Illinois
city: Indianapolis
country: United States
facility: Dawes Fretzin Dermatology Group Inc
state: Indiana
city: Overland Park
country: United States
facility: Epiphany Dermatology of Kansas, LLC
state: Kansas
city: Beverly
country: United States
facility: ActivMed Practices and Research Inc
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Henderson
country: United States
facility: J Woodson Dermatology and Associates Ltd
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center
state: New Hampshire
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Forest Hills
country: United States
facility: Forest Hills Dermatology Group
state: New York
city: Manhasset
country: United States
facility: SUNY Downstate Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital Medical Center
state: Ohio
city: Fairborn
country: United States
facility: Wright State Physicians
state: Ohio
city: Tulsa
country: United States
facility: Essential Medical Research, LLC
state: Oklahoma
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Arlington
country: United States
facility: Arlington Research Center
state: Texas
city: Corpus Christi
country: United States
facility: Driscoll Childrens Hospital
state: Texas
city: Dallas
country: United States
facility: Modern Research Associates PLLC
state: Texas
city: Houston
country: United States
facility: Mosaic Dermatology
state: Texas
city: San Antonio
country: United States
facility: Texas Dermatology and Laser Specialists
state: Texas
city: West Jordan
country: United States
facility: Jordan Valley Dermatology Center
state: Utah
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Milwaukee
country: United States
facility: Childrens Hospital of Wisconsin
state: Wisconsin
city: Brussels
country: Belgium
facility: Centre Hospitalier Universitaire Saint Pierre
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St Luc
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Calgary
country: Canada
facility: Kirk Barber Research
state: Alberta
city: Edmonton
country: Canada
facility: Stollery Children's Hospital
state: Alberta
city: Surrey
country: Canada
facility: Enverus Medical Research
state: British Columbia
city: Winnipeg
country: Canada
facility: Winnipeg Clinic Dermatology Research
state: Manitoba
city: Saint John's
country: Canada
facility: Karma Clinical Trials
state: Newfoundland and Labrador
city: Toronto
country: Canada
facility: AvantDerm
state: Ontario
city: Montreal
country: Canada
facility: CHU Saint-Justine
state: Quebec
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Praha 1
country: Czechia
facility: Fakultni nemocnice Kralovske Vinohrady
city: Praha
country: Czechia
facility: Synexus Czech sro
city: Argenteuil
country: France
facility: Centre Hospitalier Victor Dupouy Argenteuil
city: Bron cedex
country: France
facility: Centre Hospitalier Universitaire Lyon
city: Martigues
country: France
facility: Cabinet du Docteur Ruer-Mulard Mireille
city: Nantes
country: France
facility: Hotel Dieu CHU Nantes
city: Nice
country: France
facility: Centre Hospitalier Universitaire de Nice
city: Paris Cedex 15
country: France
facility: Hopital Necker
city: Quimper
country: France
facility: Centre Hospitalier de Cornouaille - Hopital Laennec
city: Saint-Priest En Jarrez
country: France
facility: CHU Saint Etienne Hopital Nord
city: Toulouse Cedex 9
country: France
facility: Centre Hospitalier Universitaire de Toulouse - Hopital Larrey
city: Valence
country: France
facility: Centre Hospitalier de Valence
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Bologna
country: Italy
facility: Azienda Ospedaliero Universitaria Di Bologna Policlinico S Orsola Malpighi
city: Cagliari
country: Italy
facility: Azienda Ospedaliera Universitaria di Cagliari
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Reggio Emilia
country: Italy
facility: Azienda Ospedaliera di Reggio Emilia Arcispedale Santa Maria Nuova
city: Roma
country: Italy
facility: Policlinico Tor Vergata
city: Roma
country: Italy
facility: Istituto Dermatologico San Gallicano IRCCS Dermatologia Clinica
city: NIjmegen
country: Netherlands
facility: Radboud university medical center
city: Barnaul
country: Russian Federation
facility: Altai State Medical University
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Clinical Skin and Venereal Dispensary
city: Ekaterinburg
country: Russian Federation
facility: Ural Scientific Research Institute of Dermatovenereology and Immunopathology
city: Kazan
country: Russian Federation
facility: Republican Clinical Dermatology and Venerology Dispensary
city: Krasnodar
country: Russian Federation
facility: Clinical Dispensary of Dermatology and Venereology of Krasnodar Territory of the Ministry of Health
city: Moscow
country: Russian Federation
facility: State Scientific Center for Dermatovenereology and Cosmetology
city: Moscow
country: Russian Federation
facility: Russian Children's Clinical Hospital
city: Moscow
country: Russian Federation
facility: Moscow Scientific Practical Center of Dermatology Venerology and Cosmetology
city: Moscow
country: Russian Federation
facility: National Medical Research Center for Children's Health
city: Novosibirsk
country: Russian Federation
facility: LLC Medical Center Zdorovaya Semiya
city: Saint Petersburg
country: Russian Federation
facility: Pierre Wolkenshtein Skin Diseases Clinic LLC
city: Saint Petersburg
country: Russian Federation
facility: LLC PiterKlinika
city: Saint Petesburg
country: Russian Federation
facility: Saint Petersburg State Pediatric Medical University
city: Ufa
country: Russian Federation
facility: Bashkiria State Medical University
city: Yaroslavl
country: Russian Federation
facility: Yarosavl State Medical Academy
city: Santander
country: Spain
facility: Hospital Marques de Valdecilla
state: Cantabria
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
state: Comunidad Valenciana
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol Can Ruti
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
city: Cadiz
country: Spain
facility: Hospital Puerta del Mar
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital La Paz
city: Pontevedra
country: Spain
facility: Complexo Hospitalario De Pontevedra
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio - PPDS
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Fiorillo L, Becker E, de Lucas R, Belloni-Fortina A, Armesto S, Elewski B, Maes P, Oberoi RK, Paris M, Zhang W, Zhang Z, Arkin L. Efficacy and safety of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 16-week results from SPROUT, a randomized controlled trial. J Am Acad Dermatol. 2024 Jun;90(6):1232-1239. doi: 10.1016/j.jaad.2023.11.068. Epub 2024 Jan 23.