Efficacy and Safety Study of Apremilast (CC-10004) in Pediatric Subjects From 6 Through 17 Years of Age With Moderate to Severe Plaque Psoriasis

Psoriasis Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03701763
• Other study ID #: CC-10004-PPSO-003
• Secondary ID: U1111-1219-31122
• Status: Terminated
• Phase: Phase 3
• Start date: December 19, 2018
• Est. completion date: March 27, 2023

Study information

• Verified date: June 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 245
• Est. completion date: March 27, 2023
• Est. primary completion date: April 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

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).

Related Conditions & MeSH terms

• Psoriasis

Intervention

Drug:
• Apremilast (CC-10004)
Apremilast (CC-10004)

Other:
• Placebo
Placebo

Locations

Country	Name	City	State
Belgium	Centre Hospitalier Universitaire Saint Pierre	Brussels
Belgium	Cliniques Universitaires St Luc	Bruxelles
Belgium	Universitair Ziekenhuis Gent	Gent
Canada	Kirk Barber Research	Calgary	Alberta
Canada	Stollery Children's Hospital	Edmonton	Alberta
Canada	CHU Saint-Justine	Montreal	Quebec
Canada	Karma Clinical Trials	Saint John's	Newfoundland and Labrador
Canada	Enverus Medical Research	Surrey	British Columbia
Canada	AvantDerm	Toronto	Ontario
Canada	Winnipeg Clinic Dermatology Research	Winnipeg	Manitoba
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	Synexus Czech sro	Praha
Czechia	Fakultni nemocnice Kralovske Vinohrady	Praha 1
France	Centre Hospitalier Victor Dupouy Argenteuil	Argenteuil
France	Centre Hospitalier Universitaire Lyon	Bron cedex
France	Cabinet du Docteur Ruer-Mulard Mireille	Martigues
France	Hotel Dieu CHU Nantes	Nantes
France	Centre Hospitalier Universitaire de Nice	Nice
France	Hopital Necker	Paris Cedex 15
France	Centre Hospitalier de Cornouaille - Hopital Laennec	Quimper
France	CHU Saint Etienne Hopital Nord	Saint-Priest En Jarrez
France	Centre Hospitalier Universitaire de Toulouse - Hopital Larrey	Toulouse Cedex 9
France	Centre Hospitalier de Valence	Valence
Israel	Chaim Sheba Medical Center	Ramat Gan
Italy	Azienda Ospedaliero Universitaria Di Bologna Policlinico S Orsola Malpighi	Bologna
Italy	Azienda Ospedaliera Universitaria di Cagliari	Cagliari
Italy	Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliera Universitaria Federico II	Napoli
Italy	Azienda Ospedaliera di Padova	Padova
Italy	Azienda Ospedaliera di Reggio Emilia Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	Istituto Dermatologico San Gallicano IRCCS Dermatologia Clinica	Roma
Italy	Policlinico Tor Vergata	Roma
Netherlands	Radboud university medical center	NIjmegen
Russian Federation	Altai State Medical University	Barnaul
Russian Federation	Chelyabinsk Regional Clinical Skin and Venereal Dispensary	Chelyabinsk
Russian Federation	Ural Scientific Research Institute of Dermatovenereology and Immunopathology	Ekaterinburg
Russian Federation	Republican Clinical Dermatology and Venerology Dispensary	Kazan
Russian Federation	Clinical Dispensary of Dermatology and Venereology of Krasnodar Territory of the Ministry of Health	Krasnodar
Russian Federation	Moscow Scientific Practical Center of Dermatology Venerology and Cosmetology	Moscow
Russian Federation	National Medical Research Center for Children's Health	Moscow
Russian Federation	Russian Children's Clinical Hospital	Moscow
Russian Federation	State Scientific Center for Dermatovenereology and Cosmetology	Moscow
Russian Federation	LLC Medical Center Zdorovaya Semiya	Novosibirsk
Russian Federation	LLC PiterKlinika	Saint Petersburg
Russian Federation	Pierre Wolkenshtein Skin Diseases Clinic LLC	Saint Petersburg
Russian Federation	Saint Petersburg State Pediatric Medical University	Saint Petesburg
Russian Federation	Bashkiria State Medical University	Ufa
Russian Federation	Yarosavl State Medical Academy	Yaroslavl
Spain	Hospital General Universitario de Alicante	Alicante	Comunidad Valenciana
Spain	Hospital Universitari Germans Trias i Pujol Can Ruti	Badalona
Spain	Hospital Sant Joan de Deu	Barcelona
Spain	Hospital Puerta del Mar	Cadiz
Spain	Hospital Universitario Reina Sofia	Cordoba
Spain	Hospital 12 de Octubre	Madrid
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Infantil Universitario Nino Jesus	Madrid
Spain	Hospital La Paz	Madrid
Spain	Complexo Hospitalario De Pontevedra	Pontevedra
Spain	Hospital Marques de Valdecilla	Santander	Cantabria
Spain	Hospital Universitario Virgen del Rocio - PPDS	Sevilla
United States	Arlington Research Center	Arlington	Texas
United States	ActivMed Practices and Research Inc	Beverly	Massachusetts
United States	Zenith Research Inc.	Beverly Hills	California
United States	University of Alabama Birmingham	Birmingham	Alabama
United States	Montefiore Medical Center	Bronx	New York
United States	Medical University of South Carolina	Charleston	South Carolina
United States	DeNova Research	Chicago	Illinois
United States	Cincinnati Childrens Hospital Medical Center	Cincinnati	Ohio
United States	Driscoll Childrens Hospital	Corpus Christi	Texas
United States	Modern Research Associates PLLC	Dallas	Texas
United States	Wright State Physicians	Fairborn	Ohio
United States	Forest Hills Dermatology Group	Forest Hills	New York
United States	Johnson Dermatology Clinic	Fort Smith	Arkansas
United States	First OC Dermatology	Fountain Valley	California
United States	J Woodson Dermatology and Associates Ltd	Henderson	Nevada
United States	Mosaic Dermatology	Houston	Texas
United States	Dawes Fretzin Dermatology Group Inc	Indianapolis	Indiana
United States	Solutions Through Advanced Research Inc	Jacksonville	Florida
United States	Avance Clinical Trials	Laguna Niguel	California
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Skin Care Physicians of Georgia	Macon	Georgia
United States	University of Wisconsin Hospital and Clinics	Madison	Wisconsin
United States	SUNY Downstate Medical Center	Manhasset	New York
United States	Glick Skin Institute Clinical Research	Margate	Florida
United States	Treasure Valley Medical Research	Meridian	Idaho
United States	Ciocca Dermatology	Miami	Florida
United States	University of Miami Hospital	Miami	Florida
United States	Childrens Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Epiphany Dermatology of Kansas, LLC	Overland Park	Kansas
United States	Stanford University	Palo Alto	California
United States	Phoenix Childrens Hospital	Phoenix	Arizona
United States	Mayo Clinic	Rochester	Minnesota
United States	Texas Dermatology and Laser Specialists	San Antonio	Texas
United States	Coastal Family Dermatology	San Luis Obispo	California
United States	University of California Los Angeles	Santa Monica	California
United States	University of South Florida Health Morsani Center for Advanced Healthcare	Tampa	Florida
United States	California Dermatology Institute	Thousand Oaks	California
United States	Essential Medical Research, LLC	Tulsa	Oklahoma
United States	Jordan Valley Dermatology Center	West Jordan	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  Czechia,  France,  Israel,  Italy,  Netherlands,  Russian Federation,  Spain, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With a Static Physician Global Assessment (sPGA) Response at Week 16	The sPGA is the assessment by the Investigator of the overall disease severity of plaque psoriasis at the time of evaluation. The sPGA is a 5-point scale ranging from 0 (clear) to 4 (severe), incorporating an assessment of the severity of the three primary signs of the disease: erythema, scaling and plaque elevation. The results presented are for the percentage of participants with a sPGA response. An sPGA response was defined as a score of clear (0) or almost clear (1) with at least a 2-point reduction from baseline at Week 16.	Baseline to Week 16
Secondary	Percentage of Participants Who Achieved At Least 75% Reduction in Psoriasis Area Severity Index (PASI-75) From Baseline at Week 16	The Psoriasis Area Severity Index (PASI) is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. The results presented are for the percentage of participants with PASI-75. PASI-75 was defined as at least a 75% reduction in PASI score from baseline.	Baseline and Week 16
Secondary	Percentage of Participants Who Achieved At Least 50% Reduction in Psoriasis Area Severity Index (PASI-50) From Baseline at Week 16	The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. The results presented are for the percentage of participants with PASI-50. PASI-50 was defined as at least a 50% reduction in PASI score from baseline.	Baseline and Week 16
Secondary	Percentage Change From Baseline in Total PASI Score at Week 16	The PASI is a measure of psoriatic disease severity taking into account qualitative lesion characteristics (erythema, thickness, and scaling) and degree of skin surface area involvement on defined anatomical regions. The PASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Positive percentage change from baseline scores indicate a worsening of disease severity, and negative percentage change from baseline scores indicate an improvement in disease severity.	Baseline and Week 16
Secondary	Percentage Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis at Week 16	BSA is a measurement of involved skin of the whole body affected by psoriasis, which ranges from 0% to 100%. Positive percentage change from baseline indicates that a greater BSA was affected by psoriasis. A negative percentage change from baseline indicates that a lesser BSA was affected by psoriasis.	Baseline and Week 16
Secondary	Percentage of Participants Who Achieved a Children's Dermatology Life Quality Index (CDLQI) Score of 0 or 1 at Week 16	The CDLQI is designed to measure the impact of skin disease on children's quality of life. The CDLQI measures how much the participant's psoriasis has affected them over the last week, and includes 10 questions with possible answers ranging from not at all (score of 0) to very much (score of 3). The CDLQI total score ranged from 0 (no effect on the participant's life) to 30 (extremely large effect on the participant's life). The results presented are for the percentage of participants who achieved a total CDLQI score of 0 or 1 at Week 16.	Week 16
Secondary	Change From Baseline in CDLQI Score at Week 16	The CDLQI is designed to measure the impact of skin disease on children's quality of life. The CDLQI measures how much the participant's psoriasis has affected them over the last week, and includes 10 questions with possible answers ranging from not at all (score of 0) to very much (score of 3). The CDLQI total score ranged from 0 (no effect on the participant's life) to 30 (extremely large effect on the participant's life). A positive change from baseline score indicates that a participant's quality of life has worsened. A negative change from baseline score indicates that a participant's quality of life has improved.	Baseline and Week 16
Secondary	Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) During the Placebo-controlled Phase	An adverse event (AE) was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of the study. A TEAE is any AE that occurred after first dose of the investigational product.	16 weeks
Secondary	Number of Participants Who Experienced a TEAE During the Apremilast Exposure Period	An AE was defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of the study. A TEAE is any AE that occurred after first dose of the investigational product.	52 weeks
Secondary	Number of Participants Who Experienced a Treatment-emergent Serious Adverse Event (TESAE) During the Placebo-controlled Phase	A TESAE is any AE occurring at any dose after first dose that results in death, is life-threatening (ie, in the opinion of the Investigator, the participant is at immediate risk of death from the AE), requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay), results in persistent or significant disability/incapacity (a substantial disruption of the participant's ability to conduct normal life functions), is a congenital anomaly/birth defect, or constitutes an important medical event.	16 weeks
Secondary	Number of Participants Who Experienced a TESAE During the Apremilast Exposure Period	A TESAE is any AE occurring at any dose after first dose that results in death, is life-threatening (ie, in the opinion of the Investigator, the participant is at immediate risk of death from the AE), requires inpatient hospitalization or prolongation of existing hospitalization (hospitalization is defined as an inpatient admission, regardless of length of stay), results in persistent or significant disability/incapacity (a substantial disruption of the participant's ability to conduct normal life functions), is a congenital anomaly/birth defect, or constitutes an important medical event.	52 weeks
Secondary	Number of Participants Who Experienced a Treatment-related Adverse Event (TRAE) During the Placebo-controlled Phase	A TREAE is any AE that is determined by the Investigator to have a possibly causal relationship to the investigational product.	16 weeks
Secondary	Number of Participants Who Experienced a TRAE During the Apremilast Exposure Period	A TREAE is any AE that is determined by the Investigator to have a possibly causal relationship to the investigational product.	52 weeks
Secondary	Number of Participants With Diarrhea During the Placebo-controlled Phase	Diarrhea was defined as having 3 or more liquid or watery stools in a day. Participants and their parent/guardian were supplied with diaries (either paper or electronic) that were filled out daily to record and describe any diarrhea and associated symptoms.	Up to approximately 113 days
Secondary	Number of Participants With Diarrhea During the Apremilast Exposure Period	Diarrhea was defined as having 3 or more liquid or watery stools in a day. Participants and their parent/guardian were supplied with diaries (either paper or electronic) that were filled out daily to record and describe any diarrhea and associated symptoms.	Day 1 up to approximately 365 days
Secondary	Number of Participants With Diarrhea Symptoms During the Placebo-controlled Phase	Diarrhea symptoms were nausea, vomiting, abdominal cramps, abdominal pain, fever, bloating, and other symptoms. Participants and their parent/guardian were supplied with diaries (either paper or electronic) that were filled out daily to record and describe any diarrhea and associated symptoms.	Up to approximately 113 days
Secondary	Number of Participants With Diarrhea Symptoms During the Apremilast Exposure Period	Diarrhea symptoms were nausea, vomiting, abdominal cramps, abdominal pain, fever, bloating, and other symptoms. Participants and their parent/guardian were supplied with diaries (either paper or electronic) that were filled out daily to record and describe any diarrhea and associated symptoms.	Day 1 up to approximately 365 days
Secondary	Number of Participants With Suicidal Ideation or Behavior Per the Columbia-Suicide Severity Rating Scale (C-SSRS) During the Placebo-controlled Phase	The C-SSRS is a questionnaire that is used to assess suicidal ideation and behavior. The C-SSRS questionnaire measures suicidal ideation, intensity of ideation, and suicidal behaviors. Results presented are for the number of participants who recorded suicidal ideation or behavior on the C-SSRS.	16 weeks
Secondary	Number of Participants With Suicidal Ideation or Behavior Per the C-SSRS During the Apremilast-extension Phase	The C-SSRS is a questionnaire that is used to assess suicidal ideation and behavior. The C-SSRS questionnaire measures suicidal ideation, intensity of ideation, and suicidal behaviors. Results presented are for the number of participants who recorded suicidal ideation or behavior on the C-SSRS.	Week 16 to Week 52
Secondary	Number of Female Participants at Stage I-V of Sexual Development Per Tanner Staging of Sexual Development	The Tanner Staging of sexual development is a scale of physical development as children transition into adolescence and then adulthood. The scale defines physical measurements of development based on characteristics, such as the size of the breasts, genitals, testicular volume, and growth of pubic hair. The scale ranges from stage I (pre-adolescent) to stage V (adult development). The results presented are for the number of participants at stage I-V of development.	Week 52
Secondary	Number of Male Participants at Stage I-V of Sexual Development Per Tanner Staging of Sexual Development	The Tanner Staging of sexual development is a scale of physical development as children transition into adolescence and then adulthood. The scale defines physical measurements of development based on characteristics, such as the size of the breasts, genitals, testicular volume, and growth of pubic hair. The scale ranges from stage I (pre-adolescent) to stage V (adult development). The results presented are for the number of participants at stage I-V of development.	Week 52
Secondary	Mean Body Weight of Participants During the Placebo-controlled Phase	The participants' body weight in kilograms (kg) was recorded.	Baseline and Week 16
Secondary	Mean Body Weight of Participants During the Apremilast Exposure Period	The participants' body weight in kilograms (kg) was recorded.	Baseline and Week 52
Secondary	Mean Height of Participants During the Placebo-controlled Phase	The participants' height in centimeters (cm) was recorded.	Baseline and Week 16
Secondary	Mean Height of Participants During the Apremilast Exposure Period	The participants' height in centimeters (cm) was recorded.	Baseline and Week 52
Secondary	Mean Body Mass Index (BMI) of Participants During the Placebo-controlled Phase	The participants' BMI was calculated as body weight (kg)/height (m^2).	Baseline and Week 16
Secondary	Mean BMI of Participants During the Apremilast Exposure Period	The participants' BMI was calculated as body weight (kg)/height (m^2).	Baseline and Week 52
Secondary	Number of Participants Who Experienced a Psoriasis Flare During the Placebo-controlled Phase	A psoriasis flare was defined as a sudden intensification of psoriasis (new generalized erythrodermic, inflammatory or pustular psoriasis) requiring medical intervention beyond allowable medications.	16 weeks
Secondary	Number of Participants Who Experienced a Psoriasis Flare During the Apremilast Exposure Period	A psoriasis flare was defined as a sudden intensification of psoriasis (new generalized erythrodermic, inflammatory or pustular psoriasis) requiring medical intervention beyond allowable medications.	52 weeks
Secondary	Number of Participants Who Experienced a Psoriasis Rebound	A psoriasis rebound was defined as an adverse event of psoriasis that started after the last dose date for participants who received treatment in the study.	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)

External Links

•   AmgenTrials clinical trials website