An Efficacy, Safety, and Pharmacokinetics Study of Subcutaneously Administered Ustekinumab in the Treatment of Moderate to Severe Chronic Plaque Psoriasis in Pediatric Participants Greater Than or Equal to 6 to Less Than 12 Years of Age (CADMUS Jr)

• ClinicalTrials.gov Identifier: NCT02698475
• Recruitment Status: Completed
• First Posted: March 3, 2016
• Results First Posted: August 28, 2020
• Last Update Posted: November 1, 2021
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Study Description

Brief Summary:

The purpose of this study is to evaluate the efficacy and safety of ustekinumab in pediatric participants aged greater than or equal to (>=) 6 through less than (<) 12 years with moderate to severe chronic plaque psoriasis

Condition or disease	Intervention/treatment	Phase
Psoriasis	Drug: Ustekinumab 0.75 mg/kg; Drug: Ustekinumab 45 mg; Drug: Ustekinumab 90 mg	Phase 3

Detailed Description:

This is an open label (identity of study drug will be known to participant and study staff) and multicenter (when more than one hospital or medical school team work on a medical research study) study. The participant population will be comprised of boys and girls who have had a diagnosis of plaque psoriasis for at least 6 months prior to first study drug administration and who have moderate to severe disease defined by Psoriasis Area and Severity Index score (PASI) >=12, Physician's Global Assessment (PGA) >=3, and Body Surface Area (BSA) >=10 percent (%). The study consists of Screening Phase (up to 10 weeks before administration of the study drug), Treatment Period (Week 0 up to Week 52) and Safety follow up (Week 56). Participants will be primarily evaluated for efficacy, pharmacokinetics (PK) and safety. Following completion of the Week 52 visit, participants who have had a beneficial response from ustekinumab treatment as determined by the investigator, and who have not yet reached the age of 12 years or older in countries where marketing authorization for ustekinumab has been granted for the treatment of psoriasis in adolescent participants (12-17 years), and are willing to continue ustekinumab treatment, may enter the long-term extension period (from Week 56 through Week 264) of the study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Open-label Study to Assess the Efficacy, Safety, and Pharmacokinetics of Subcutaneously Administered Ustekinumab in the Treatment of Moderate to Severe Chronic Plaque Psoriasis in Pediatric Subjects Greater Than or Equal to 6 to Less Than 12 Years of Age
• Actual Study Start Date: May 2016
• Actual Primary Completion Date: December 2017
• Actual Study Completion Date: October 2020

Arms and Interventions

Arm

Intervention/treatment

Experimental: Ustekinumab Group; Participants will receive 1 of the following dose levels depending on their weight: participants weighing less than (<) 60 kg will receive Ustekinumab 0.75 milligram per kilogram (mg/kg); participants weighing greater than or equal to (>=) 60 kg to less than or equal to (<=) 100 kg will receive ustekinumab 45 mg; participants weighing >100 kg will receive ustekinumab 90 mg, at Weeks 0 and 4 followed by every 12 weeks dosing with the last dose at Week 40. Eligible participants who enter the long-term extension (LTE) period will continue receiving ustekinumab every 12 weeks (q12w) beginning at Week 56 up to Week 248.

Drug: Ustekinumab 0.75 mg/kg; Participants weighing less than (<) 60 kilograms will receive ustekinumab 0.75 milligram per kilogram (mg/kg) at Weeks 0 and 4 followed by every 12 weeks dosing with the last dose at Week 40. Eligible participants for LTE period will continue to receive ustekinumab 0.75 mg/kg up to Week 248.; Drug: Ustekinumab 45 mg; Participants weighing greater than or equal to (>=) 60 kg to less than or equal to (<=) 100 kg will receive ustekinumab 45 mg at Weeks 0 and 4 followed by every 12 weeks dosing with the last dose at Week 40. Eligible participants for LTE period will continue to receive ustekinumab 45 mg up to Week 248.; Drug: Ustekinumab 90 mg; Participants weighing >100 kg will receive ustekinumab 90 mg at Weeks 0 and 4 followed by every 12 weeks dosing with the last dose at Week 40. Eligible participants for LTE period will continue to receive ustekinumab 90 mg up to Week 248.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Physician's Global Assessment (PGA) Score of Cleared (0) or Minimal (1) at Week 12 [ Time Frame: Week 12 ]
   The PGA is used to determine the participant's psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The participant's psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), marked (4), or severe (5). Higher scores indicate worse disease. Treatment Failure (TF) criteria- discontinued study agent due to lack of efficacy or adverse event of psoriasis or who started protocol-prohibited medication/therapy.

Secondary Outcome Measures :

1. Percentage of Participants Who Achieved Psoriasis Area and Severity Index (PASI) 75 Response at Week 12 [ Time Frame: Week 12 ]
   PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90%-100% involvement), and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4 that is none to maximum severity. The PASI produces a numeric score that can range from 0 (no psoriasis) to 72. A higher score indicates more severe disease. Participants with >=75% improvement in PASI from baseline were considered PASI 75 responders. TF criteria- discontinued study agent due to lack of efficacy or adverse event of psoriasis or who started protocol-prohibited medication/therapy.
2. Change From Baseline in Children Dermatology Life Quality Index (CDLQI) Score at Week 12 [ Time Frame: Baseline and Week 12 ]
   CDLQI was used to assess the impact of psoriasis on subject health-related quality of life. The CDLQI has 10 items assessing health-related quality of life (HRQOL) in patients with skin disease each measured on a scale from 0 (Not at all) to 3 (Very much). The total score ranges from 0 to 30, with lower scores indicating better quality of life. The higher the score, the greater the impairment in quality of life (QoL). TF criteria- discontinued study agent due to lack of efficacy or adverse event of psoriasis or who started protocol-prohibited medication/therapy.
3. Percentage of Participants Who Achieved PASI 90 Response at Week 12 [ Time Frame: Week 12 ]
   PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90%-100% involvement), and for erythema, induration, and scaling, which are each rated on a scale of 0 to 4 that is none to maximum severity. The PASI produces a numeric score that can range from 0 (no psoriasis) to 72 (disease severity). A higher score indicates more severe disease. Participants with >=90% improvement in PASI from baseline were considered PASI 90 responders. TF criteria- discontinued study agent due to lack of efficacy or adverse event of psoriasis or who started protocol-prohibited medication/therapy.
4. Percentage of Participants With a PGA Score of Cleared (0), Cleared (0) or Minimal (1), Mild (2) at Weeks 4, 8, 12, 16, 28, 40, and 52 [ Time Frame: Weeks 4, 8, 12, 16, 28, 40, and 52 ]
   The PGA is used to determine the participant's psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The participant's psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), marked (4), or severe (5). Higher scores indicate worse disease. TF criteria- discontinued study agent due to lack of efficacy or adverse event of psoriasis or who started protocol-prohibited medication/therapy.
5. Percentage of Participants Who Achieved a PASI 50, PASI 75, PASI 90 and PASI 100 Response at Weeks 4, 8, 12, 16, 28, 40, and 52 [ Time Frame: Weeks 4, 8, 12, 16, 28, 40, and 52 ]
   The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4 that is none to maximum severity. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72 (disease severity). PASI 50, 75, 90, and 100 responders were defined as >=50%, >=75%, >=90%, and 100% improvement in PASI from Baseline respectively. TF criteria- discontinued study agent due to lack of efficacy or adverse event of psoriasis or who started protocol-prohibited medication/therapy.
6. Percent Change From Baseline in PASI Score at Weeks 4, 8, 12, 16, 28, 40, and 52 [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 28, 40, 52 ]
   The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4 that is none to maximum severity. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72 (disease severity). PASI 100 responders were defined as 100% improvement in PASI from Baseline respectively. TF criteria- discontinued study agent due to lack of efficacy or adverse event of psoriasis or who started protocol-prohibited medication/therapy.
7. Percentage of Participants Who Achieved PASI 100, PASI 90, PASI 75 or PASI 50 Response in PASI Components (Induration, Erythema, and Scaling) and Region Components (Head, Trunk, Upper Extremities, and Lower Extremities) at Week 12 [ Time Frame: Week 12 ]
   The PASI is a system used for assessing and grading the severity of psoriatic lesions and their response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed separately for the percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates no involvement) to 6 (90 percentage (%)-100% involvement), and for erythema, induration and scaling, which are each rated on a scale of 0 to 4 that is none to maximum severity. The PASI produces a numeric score that could range from 0 (no psoriasis) to 72 (disease severity). PASI 50, 75, 90, and 100 responders were defined as >=50%, >=75%, >=90%, and 100% improvement in PASI component from Baseline respectively. TF criteria- discontinued study agent due to lack of efficacy or adverse event of psoriasis or who started protocol-prohibited medication/therapy.
8. Change From Baseline in Children Dermatology Life Quality Index (CDLQI) Score at Weeks 4, 12, 28, and 52 [ Time Frame: Baseline and Weeks 4, 12, 28, 52 ]
   CDLQI was used to assess the impact of psoriasis on subject health-related quality of life. The CDLQI has 10 items assessing health-related quality of life (HRQOL) in patients with skin disease each measured on a scale from 0 (Not at all) to 3 (Very much). The total score ranges from 0 to 30. The higher the score, the greater the impairment in quality of life (QoL). TF criteria- discontinued study agent due to lack of efficacy or adverse event of psoriasis or who started protocol-prohibited medication/therapy.
9. Percentage of Participants With a CDLQI Score of 0 or 1 at Week 12 in Participants With a Baseline CDLQI Score Greater Than (>) 1 [ Time Frame: Week 12 ]
   CDLQI was used to assess the impact of psoriasis on subject health-related quality of life. The CDLQI has 10 items assessing health-related quality of life (HRQOL) in patients with skin disease each measured on a scale from 0 (Not at all) to 3 (Very much). The total score ranges from 0 to 30. The higher the score, the greater impairment in quality of life. TF criteria- discontinued study agent due to lack of efficacy or adverse event of psoriasis or who started protocol-prohibited medication/therapy.
10. Percentage of Participants With a CDLQI Score of 0 or 1 at Weeks 4, 12, 28 and 52 in Participants With a Baseline CDLQI Score > 1 [ Time Frame: Weeks 4, 12, 28, and 52 ]
    CDLQI was used to assess the impact of psoriasis on subject health-related quality of life. The CDLQI has 10 items assessing health-related quality of life (HRQOL) in patients with skin disease each measured on a scale from 0 (Not at all) to 3 (Very much). The total score ranges from 0 to 30. The total score ranges from 0 to 30. The higher the score, the greater impairment in quality of life. TF criteria- discontinued study agent due to lack of efficacy or adverse event of psoriasis or who started protocol-prohibited medication/therapy.
11. Change From Baseline in CDLQI Component Scores at Week 12 [ Time Frame: Baseline and Week 12 ]
    CDLQI was used to assess the impact of psoriasis on subject health-related quality of life. The CDLQI has 10 items assessing health-related quality of life (HRQOL) in patients with skin disease each measured on a scale from 0 (Not at all) to 3 (Very much). The total score ranges from 0 to 30. The total score ranges from 0 to 30. The higher the score, the greater impairment in quality of life. TF criteria- discontinued study agent due to lack of efficacy or adverse event of psoriasis or who started protocol-prohibited medication/therapy.
12. Percentage of Participants With PGA Score of Cleared (0), Cleared (0) or Minimal (1), Cleared (0) or Minimal (1) or Mild (2) at Weeks 80, 104, 128, 152, and 176 [ Time Frame: Weeks 80, 104, 128, 152, 176 ]
    The PGA is used to determine the participant's psoriasis at a given time point. Overall lesions are graded for induration, erythema, and scaling. The participant's psoriasis was assessed as cleared (0), minimal (1), mild (2), moderate (3), marked (4), or severe (5). Higher scores indicated worse disease.

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 11 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Participants who have a diagnosis of plaque-type psoriasis with or without psoriatic arthritis (PsA) for at least 6 months prior to first administration of study drug, with widespread lesions defined by Psoriasis Area and Severity Index score (PASI) greater than or equal to (>=) 12, Physician's Global Assessment (PGA) >=3, and involved body surface area (BSA) >=10 percent (%)
• Participants who are candidates for phototherapy or systemic treatment of psoriasis (either naive or history of previous treatment) or have psoriasis considered by the investigator as poorly controlled with topical therapy after an adequate dose and duration of therapy
• Participants who are considered eligible according to the protocol defined tuberculosis (TB) screening criteria
• Participants must have positive protective antibody titers to varicella and measles prior to the first administration of study drug. In the absence of positive protective antibody titers, the participant must have documentation of age-appropriate vaccination for varicella and/or measles (that includes both doses of each vaccine) or verification of past varicella and/or measles infection documented by a health care provider
• Participants must agree not to receive a live virus or live bacterial vaccination at least 2 weeks (or longer as indicated in the package insert of the relevant vaccine) prior to the first administration of study drug, during the study, or within 15 weeks after the last administration of study drug
• Participants must agree not to receive a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening, during the study, or within 12 months after the last administration of study drug

Exclusion Criteria:

• Participants who currently have nonplaque forms of psoriasis (example, erythrodermic, guttate, or pustular)
• Have received any systemic immunosuppressants (example methotrexate [MTX], azathioprine, cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil, hydroxyurea, and tacrolimus) within 4 weeks of the first administration of study drug
• Have received any biologic agent (example ENBREL, HUMIRA) within the previous 3 months or 5 times the t1/2 of the agent, whichever is longer
• Have a history of chronic or recurrent infectious disease
• Have a history of latent or active granulomatous infection
• Have any known malignancy or have a history of malignancy
• Have a known history of lymphoproliferative disease, including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease

Contacts and Locations

Locations

United States, California

San Diego, California, United States

United States, Illinois

Chicago, Illinois, United States

United States, Indiana

Indianapolis, Indiana, United States

United States, Missouri

Saint Louis, Missouri, United States

United States, Texas

Arlington, Texas, United States

Dallas, Texas, United States

United States, Virginia

Norfolk, Virginia, United States

Belgium

Brussels, Belgium

Gent, Belgium

Liege, Belgium

Canada, Alberta

Calgary, Alberta, Canada

Canada, Newfoundland and Labrador

St. John's, Newfoundland and Labrador, Canada

Germany

Berlin, Germany

Bonn, Germany

Dresden, Germany

Frankfurt, Germany

Hungary

Budapest, Hungary

Debrecen, Hungary

Kaposvar, Hungary

Kecskemet, Hungary

Szeged, Hungary

Korea, Republic of

Bundang, Korea, Republic of

Incheon, Korea, Republic of

Seoul, Korea, Republic of

Netherlands

Nijmegen, Netherlands

Poland

Lodz, Poland

Warszawa, Poland

Wroclaw, Poland

Taiwan

Kaohsiung, Taiwan

Taipei, Taiwan

Taoyuan, Taiwan

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

  Study Documents (Full-Text)

Documents provided by Janssen Research & Development, LLC:

Study Protocol  [PDF] May 18, 2017

Statistical Analysis Plan  [PDF] February 8, 2018

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Leu JH, Shiff NJ, Clark M, Bensley K, Lomax KG, Berezny K, Nelson RM, Zhou H, Xu Z. Intravenous Golimumab in Patients with Polyarticular Juvenile Idiopathic Arthritis and Juvenile Psoriatic Arthritis and Subcutaneous Ustekinumab in Patients with Juvenile Psoriatic Arthritis: Extrapolation of Data from Studies in Adults and Adjacent Pediatric Populations. Paediatr Drugs. 2022 Nov;24(6):699-714. doi: 10.1007/s40272-022-00533-y. Epub 2022 Sep 28.

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT02698475
• Other Study ID Numbers: CR108129; CNTO1275PSO3013 ( Other Identifier: Janssen Research & Development, LLC ); 2016-000121-40 ( EudraCT Number )
• First Posted: March 3, 2016
• Results First Posted: August 28, 2020
• Last Update Posted: November 1, 2021
• Last Verified: September 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:

Psoriasis; Ustekinumab; STELARA

Additional relevant MeSH terms:

Psoriasis; Skin Diseases, Papulosquamous; Skin Diseases; Ustekinumab; Dermatologic Agents