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

AbbVie

Status and phase: Completed; Phase 3

Conditions: Plaque Psoriasis

Treatments: Biological: Placebo to Adalimumab; Drug: Placebo to Methotrexate; Biological: Adalimumab; Drug: Methotrexate

Study type: Interventional

Funder types: Industry

Identifiers

NCT01251614

M04-717

2009-013072-52 (EudraCT Number)

Details and patient eligibility

About

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.

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Period B - Treatment Withdrawal Phase: Responders were withdrawn from active treatment and monitored for loss of disease control for up to 36 weeks.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

Enrollment: 114 patients

Sex: All

Ages: 4 to 17 years old

Volunteers: No Healthy Volunteers

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;

3. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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114 participants in 3 patient groups

Adalimumab 0.4 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Placebo to Methotrexate

Biological: Adalimumab

Adalimumab 0.8 mg/kg

Experimental group

Description:

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.

Treatment:

Drug: Placebo to Methotrexate

Biological: Adalimumab

Methotrexate

Active Comparator group

Description:

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.

Treatment:

Biological: Placebo to Adalimumab

Drug: Methotrexate