A Double Blind Study in Pediatric Subjects With Chronic Plaque Psoriasis, Studying Adalimumab vs. Methotrexate

NCT01251614 | Completed Phase 3 Results DMC

• 2 other identifiers: M04-7172009-013072-52
• Study Type: interventional
• Target: 114
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Plaque Psoriasis

Keywords

Randomized; Double-blind; Chronic plaque psoriasis; Pediatric

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI) 75 Response at Week 16

  PASI is a composite score based on the degree of effect on body surface area of psoriasis and the extension of erythema (reddening), induration (plaque thickness), desquamation (scaling) of the lesions and area affected as observed on the day of examination. The score ranges from 0 (no psoriasis) to 72 (very severe psoriasis). A PASI 75 response is defined as at least a 75% reduction (improvement) from Baseline in PASI score at Week 16.

  Baseline and Week 16

• Percentage of Participants Achieving a Physician's Global Assessment of Disease Activity (PGA) of "Cleared" (0) or "Minimal" (1) at Week 16

  The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. The degree of overall lesion severity was evaluated using the following categories: * 0 (Cleared): No evidence of scaling, erythema, or plaque elevation; * 1 (Minimal): Occasional fine scale over \<5% of lesions, faint erythema, minimal plaque elevation; * 2 (Mild): Fine scale dominates, light red coloration, mild plaque elevation; * 3 (Moderate): Course scale dominates, moderate red coloration, moderate plaque elevation; * 4 (Marked): Thick non-tenacious scale dominates, bright red coloration, marked plaque elevation; * 5 (Severe): Very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation. The percentage of participants achieving a score of clear (0) or minimal (1) is reported.

  Week 16

Secondary Outcomes (18)

• Percentage of Participants Who Achieved a PASI 90 Response at Week 16

  Baseline and Week 16

• Percentage of Participants Who Achieved a PASI 100 Response at Week 16

  Baseline and Week 16

• Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) Score at Week 16

  Baseline and Week 16

• Change From Baseline in the Pediatric Quality of Life Inventory (PedsQL) Score at Week 16

  Baseline and Week 16

• Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Upon Re-Treatment in Period C

  Period C, Week 16

Study Arms (3)

Adalimumab 0.4 mg/kg

EXPERIMENTAL

In Period A participants received a single subcutaneous loading dose of adalimumab 0.4 mg/kg (up to a maximum of 20 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets. Participants who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Participants who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Participants who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.4 mg/kg eow for 16 weeks. Participants who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Participants who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.4 mg/kg eow.

Biological: Adalimumab; Drug: Placebo to Methotrexate

Adalimumab 0.8 mg/kg

EXPERIMENTAL

In Period A participants received a single subcutaneous loading dose of adalimumab 0.8 mg/kg (up to a maximum of 40 mg) at Week 0 followed by every other week dosing beginning at Week 1. To maintain the blind, participants also received weekly dosing of methotrexate placebo tablets. Participants who were non-responders in Period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Participants who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Participants who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Participants who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Participants who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.

Biological: Adalimumab; Drug: Placebo to Methotrexate

Methotrexate

ACTIVE COMPARATOR

Participants received 0.1 mg/kg methotrexate at Baseline (Week 0), and up to 0.4 mg/kg weekly (maximum dose of 25 mg/week) in Period A. Participants also received adalimumab placebo as a single subcutaneous loading dose at Week 0, followed by every other week (eow) dosing from Week 1. Participants who were non-responders in period A entered Period D directly and received open-label adalimumab at 0.8 mg/kg eow for up to 52 weeks. Participants who responded in Period A entered the Treatment Withdrawal Phase (Period B) for up to 36 weeks. Participants who experienced a loss of disease control in Period B entered the Re-treatment Phase (Period C) and received blinded adalimumab 0.8 mg/kg eow for 16 weeks. Participants who completed Period B with no loss of disease control entered Period D and were observed off study medication for up to 52 weeks. Participants who completed Period C entered Period D for an additional 52 weeks of treatment with blinded adalimumab 0.8 mg/kg eow.

Drug: Methotrexate; Biological: Placebo to Adalimumab

Interventions

Adalimumab BIOLOGICAL

Adalimumab by subcutaneous injection every other week (eow)

Also known as: ABT-D2E7, Humira

Adalimumab 0.4 mg/kg; Adalimumab 0.8 mg/kg

Methotrexate DRUG

Methotrexate 0.1 mg/kg at Week 0 and up to 0.4 mg/kg per week (maximum dose of 25 mg/week) orally.

Methotrexate

Placebo to Adalimumab BIOLOGICAL

A single subcutaneous loading dose at Week 0 followed by eow dosing beginning at Week 1.

Methotrexate

Placebo to Methotrexate DRUG

Orally once a week

Adalimumab 0.4 mg/kg; Adalimumab 0.8 mg/kg

Eligibility Criteria

• Age: 4 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subject is ≥ 4 years and \< 18 years of age;
• Subject weighs ≥ 13 kg;
• Subject must have failed to respond to topical therapy;
• 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
• 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;

You may not qualify if:

• Prior biologic use other than prior treatment with etanercept;
• 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;
• \. 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.

Sponsors & Collaborators

• AbbVie (prior sponsor, Abbott): lead

Related Publications (2)

• 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.

  PMID: 28478975 RESULT

• 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.

  PMID: 30054164 DERIVED

Related Links

• Related Info

MeSH Terms

Interventions

Adalimumab; Methotrexate

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie (prior sponsor Abbott)

800-633-9110

Study Officials

• David A Williams, MD

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2010
• First Posted: December 2, 2010
• Study Start: December 1, 2010
• Primary Completion: December 1, 2013
• Study Completion: February 1, 2015
• Last Updated: September 25, 2017
• Results First Posted: April 4, 2017

Record last verified: 2017-08