Clinical trial NCT01251614: A Double Blind Study in Pediatric Subjects With Chronic Plaque Psoriasis, Studying Adalimumab vs. Methotrexate
Official title: A Multicenter, Randomized, Double-dummy, Double-blind Study Evaluating Two Doses of Adalimumab Versus Methotrexate (MTX) in Pediatric Subjects With Chronic Plaque Psoriasis (Ps)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Plaque Psoriasis
Keywords: Randomized
Double-blind
Chronic plaque psoriasis
Pediatric
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2010-12-02
Enrollment: 114
Sex: ALL
Minimum age (years): 4
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will compare how well adalimumab works versus methotrexate (MTX) in children with moderate to severe psoriasis in the short term. It will also study how safe and how well adalimumab works in the long term and how long disease response can be maintained after stopping therapy.

Detailed description: The study had a 30-day screening period and a multi-period study design, as described below:

Period A - Primary Treatment Phase: Participants were randomized to receive adalimumab 0.8 mg/kg, adalimumab 0.4 mg/kg, or MTX in 1:1:1 ratio for 16 weeks.

Period B - Treatment Withdrawal Phase: Responders were withdrawn from active treatment and monitored for loss of disease control for up to 36 weeks.

Period C - Re-Treatment Phase: Participants who had experienced loss of disease control in Period B were re-treated with adalimumab for 16 weeks.

Period D - Long-Term Follow-Up Phase: Participants received adalimumab or were observed off-treatment (if disease remained under control) for 52 weeks.

Eligibility criteria: Inclusion Criteria:

1. Subject is ≥ 4 years and \< 18 years of age;
2. Subject weighs ≥ 13 kg;
3. Subject must have failed to respond to topical therapy;
4. Subject must need systemic treatment to control his/her disease and meet one of the following:

   * Physician's Global Assessment (PGA) ≥ 4
   * Body surface area (BSA) involved \> 20%
   * Very thick lesions with BSA \> 10%
   * Psoriasis Area and Severity Index (PASI) \> 20
   * PASI \> 10 and at least one of the following:

     * Active psoriatic arthritis unresponsive to non-steroid anti-inflammatory drugs (NSAIDs)
     * Clinically relevant facial involvement
     * Clinically relevant genital involvement
     * Clinically relevant hand and/or foot involvement
     * Children's Dermatology Life Quality Index (CDLQI) \> 10
5. If subject is \< 12 years of age and resides in a geographic region where heliotherapy is practical, subject must have failed to respond, be intolerant, or have a contraindication to heliotherapy, or is not a suitable candidate for heliotherapy;
6. If ≥ 12 years of age, subject must have failed to respond, be intolerant, or have a contraindication to phototherapy, or is not a suitable candidate for phototherapy;
7. Subject must have a clinical diagnosis of psoriasis for at least 6 months as determined by the subject's medical history and confirmation of diagnosis through physical examination by the Investigator;
8. Subject must have stable plaque psoriasis for at least 2 months prior to Baseline

Exclusion Criteria:

1. Prior biologic use other than prior treatment with etanercept;
2. Treatment with etanercept therapy within 4 weeks prior to the Baseline visit; 3. Methotrexate (MTX) use within the past year or prior MTX use at any time where the subject did not respond, or did not tolerate MTX;

4. Contraindication for treatment with MTX during the study; 5. Erythrodermic psoriasis, generalized or localized pustular psoriasis, medication-induced or medication exacerbated psoriasis or new onset guttate psoriasis; 6. Infection(s) requiring treatment with intravenous (IV) anti-infectives within 30 days prior to the Baseline Visit or oral anti-infectives within 14 days prior to the Baseline Visit; 7. Treatment of psoriasis with topical therapies such as corticosteroids, vitamin D analogs, or retinoids within 7 days prior to the Baseline visit; 8. Treatment of psoriasis with ultraviolet (UV)B phototherapy, excessive sun exposure, or the use of tanning beds within 7 days prior to the Baseline visit; 9. Treatment of psoriasis with ultraviolet A with psoralen (PUVA) phototherapy, non-biologic systemic therapies for the treatment of psoriasis, or systemic therapies known to improve psoriasis within 14 days prior to the Baseline visit.

Primary outcomes:
measure: Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI) 75 Response at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants Achieving a Physician's Global Assessment of Disease Activity (PGA) of "Cleared" (0) or "Minimal" (1) at Week 16
timeFrame: Week 16
Secondary outcomes:
measure: Percentage of Participants Who Achieved a PASI 90 Response at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants Who Achieved a PASI 100 Response at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) Score at Week 16
timeFrame: Baseline and Week 16
measure: Change From Baseline in the Pediatric Quality of Life Inventory (PedsQL) Score at Week 16
timeFrame: Baseline and Week 16
measure: Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Upon Re-Treatment in Period C
timeFrame: Period C, Week 16
measure: Time to Loss of Disease Control for Participants Who Entered Period B
timeFrame: Period B (36 weeks) and Period D (52 weeks)
measure: Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Over Time
timeFrame: Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
measure: Percentage of Participants Achieving a PGA of "Cleared" (0) Over Time
timeFrame: Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
measure: Percentage of Participants Who Achieved a PASI 50 Response Over Time
timeFrame: Baseline, Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
measure: Percentage of Participants Who Achieved a PASI 75 Response Over Time
timeFrame: Baseline, Period A, Weeks 4, 8, and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
measure: Percentage of Participants Who Achieved a PASI 90 Response Over Time
timeFrame: Baseline, Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
measure: Percentage of Participants Who Achieved a PASI 100 Response Over Time
timeFrame: Baseline, Period A, Weeks 4, 8, and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
measure: Percent Change From Baseline in PASI Score Over Time
timeFrame: Baseline, Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
measure: Change From Baseline in CDLQI Over Time
timeFrame: Baseline, Period A, Weeks 4, and 8, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52
measure: Percentage of Participants With CDLQI = 0 Over Time
timeFrame: Period A, Weeks 4, 8 and 16, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52
measure: Time to PASI 50/75/90/100 Response in Period A
timeFrame: Period A, 16 weeks
measure: Change From Baseline in PedsQL Over Time
timeFrame: Baseline, Period A, Weeks 4 and 8, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52
measure: Change From Baseline in the Children's Depression Inventory: Short (CDI:S)
timeFrame: Baseline, Period A, Weeks 4, 8, and 16
Other outcomes:
Locations:
Study officials:
affiliation: AbbVie
name: David A Williams, MD
role: STUDY_DIRECTOR
References:
citation: Papp K, Thaci D, Marcoux D, Weibel L, Philipp S, Ghislain PD, Landells I, Hoeger P, Kotkin C, Unnebrink K, Seyger M, Williams D. Efficacy and safety of adalimumab every other week versus methotrexate once weekly in children and adolescents with severe chronic plaque psoriasis: a randomised, double-blind, phase 3 trial. Lancet. 2017 Jul 1;390(10089):40-49. doi: 10.1016/S0140-6736(17)31189-3. Epub 2017 May 4.
citation: Horneff G, Seyger MMB, Arikan D, Kalabic J, Anderson JK, Lazar A, Williams DA, Wang C, Tarzynski-Potempa R, Hyams JS. Safety of Adalimumab in Pediatric Patients with Polyarticular Juvenile Idiopathic Arthritis, Enthesitis-Related Arthritis, Psoriasis, and Crohn's Disease. J Pediatr. 2018 Oct;201:166-175.e3. doi: 10.1016/j.jpeds.2018.05.042. Epub 2018 Jul 25.