Plaque PsoriasisPhase 3NCT01251614
A Double Blind Study in Pediatric Subjects With Chronic Plaque Psoriasis, Studying Adalimumab vs. Methotrexate
A Phase 3 study testing Adalimumab and Methotrexate in people with Plaque Psoriasis, run by AbbVie (prior sponsor, Abbott).
Trial 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. Read more about this study
- Who is it for?
- Ages 4 to 17 years
- Conditions the study is for
- Plaque Psoriasis
- What is being tested?
- Adalimumab and Methotrexate
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 114 participants
- Where
- No sites listed yet
- Study dates
- Dec 2010to Feb 2015
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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%
Show all 18Show fewer
- 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;
- 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;
- 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;
- Subject must have stable plaque psoriasis for at least 2 months prior to Baseline
Who cannot join
- 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;
- 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.
About this study
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)
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.
Read the 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.
- Conditions
- Plaque Psoriasis
- Being tested
- Adalimumab, Methotrexate, Placebo to Adalimumab, Placebo to Methotrexate
- Keywords
- Randomized, Double-blind, Chronic plaque psoriasis, Pediatric
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AdalimumabBiological
Also called ABT-D2E7, Humira
Adalimumab by subcutaneous injection every other week (eow)
MethotrexateDrug
Methotrexate 0.1 mg/kg at Week 0 and up to 0.4 mg/kg per week (maximum dose of 25 mg/week) orally.
Placebo to AdalimumabBiological
A single subcutaneous loading dose at Week 0 followed by eow dosing beginning at Week 1.
Placebo to MethotrexateDrug
Orally once a week
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Methotrexate; Biological: Placebo to Adalimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Week 16
Secondary outcomes (18)
Percentage of Participants Who Achieved a PASI 90 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 90 response is at least a 90% reduction (improvement) from Baseline in PASI score at Week 16.
Measured: Baseline and Week 16
Percentage of Participants Who Achieved a PASI 100 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 100 response is a 100% reduction (improvement) from Baseline in PASI score at Week 16.
Measured: Baseline and Week 16
Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) Score at Week 16
The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.
Measured: Baseline and Week 16
Change From Baseline in the Pediatric Quality of Life Inventory (PedsQL) Score at Week 16
The PedsQL Measurement Model measures health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL Generic Core Scale includes Physical, Emotional, Social, School Functioning dimensions. Each item is scored from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better HRQOL; the total score therefore ranges from 0 (worst) to 100 (best).
Measured: Baseline and Week 16
Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Upon Re-Treatment in Period C
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.
Measured: Period C, Week 16
Time to Loss of Disease Control for Participants Who Entered Period B
Loss of disease control was defined as a worsening of PGA scores in comparison to Week 16 of Period A by at least 2 grades after treatment withdrawal. The PGA is a 6-point scale used to measure the severity of disease at the time of the evaluation. Scores range from 0 (no evidence of scaling, erythema, or plaque elevation) to 5 (very thick tenacious scale predominates, dusky to deep red coloration, severe plaque elevation).
Participants who did not lose disease control in period B continued off drug into period D and were observed off-drug until they finally lost disease control or until the end of the 52 weeks of period D.
Measured: Period B (36 weeks) and Period D (52 weeks)
Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Over Time
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.
Measured: Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Percentage of Participants Achieving a PGA of "Cleared" (0) Over Time
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) is reported.
Measured: Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Percentage of Participants Who Achieved a PASI 50 Response Over Time
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 50 response is at least a 50% reduction (improvement) from Baseline in PASI score.
Measured: Baseline, Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Percentage of Participants Who Achieved a PASI 75 Response Over Time
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 at least a 75% reduction (improvement) from Baseline in PASI score.
Measured: Baseline, Period A, Weeks 4, 8, and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Percentage of Participants Who Achieved a PASI 90 Response Over Time
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 90 response is at least a 90% reduction (improvement) from Baseline in PASI score.
Measured: Baseline, Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Percentage of Participants Who Achieved a PASI 100 Response Over Time
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 100 response is a 100% reduction (improvement) from Baseline in PASI score.
Measured: Baseline, Period A, Weeks 4, 8, and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Percent Change From Baseline in PASI Score Over Time
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).
Measured: Baseline, Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Change From Baseline in CDLQI Over Time
The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.
Measured: Baseline, Period A, Weeks 4, and 8, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52
Percentage of Participants With CDLQI = 0 Over Time
The Children's Dermatology Life Quality Index (CDLQI) is a 10-item questionnaire to measure the quality of life in children aged from 4 to 16 years. Each question is scored from 0 (not at all) to 3 (very much). The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired and a score of 0 indicates no impairment in quality of life.
Measured: Period A, Weeks 4, 8 and 16, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52
Time to PASI 50/75/90/100 Response in Period A
Participants who did not have a response during Period A were censored.
Measured: Period A, 16 weeks
Change From Baseline in PedsQL Over Time
The PedsQL Measurement Model measures health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL Generic Core Scale includes Physical, Emotional, Social, School Functioning dimensions. Each item is scored from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better HRQOL; the total score therefore ranges from 0 (worst) to 100 (best).
Measured: Baseline, Period A, Weeks 4 and 8, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52
Change From Baseline in the Children's Depression Inventory: Short (CDI:S)
The CDI:S is a short 10-item self-rated symptom-oriented scale used to screen for depressive symptoms. CDI:S scores range from 0 to 100, with a lower score indicating fewer depressive symptoms.
Measured: Baseline, Period A, Weeks 4, 8, and 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2010 (estimated)
- Study startDec 2010
- Primary completionDec 2013
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Plaque PsoriasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie (prior sponsor, Abbott)
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David A Williams, MD, Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01251614
- Sponsor's protocol ID
- M04-717
- Other IDs
- 2009-013072-52, 2009
- Status last verified
- Aug 2017
- First submitted
- 1 Dec 2010
- Last updated
- 25 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 28478975Horneff 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.
PubMed 30054164
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01251614
- Acronym / sponsor ID
- M04-717
- Conditions
- Plaque Psoriasis
- Keywords
- Randomized, Double-blind, Chronic plaque psoriasis, Pediatric
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- AbbVie (prior sponsor, Abbott)Industry (pharma, biotech, devices)
- Study start
- Dec 2010
- Primary completion
- Dec 2013 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 2 Dec 2010 (estimated)
- Results
- Posted 4 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Adalimumab 0.4 mg/kg | Experimental | Biological: Adalimumab, Drug: Placebo to MethotrexateIn 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. |
| Adalimumab 0.8 mg/kg | Experimental | Biological: Adalimumab, Drug: Placebo to MethotrexateIn 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. |
| Methotrexate | Active comparator | Drug: Methotrexate, Biological: Placebo to AdalimumabParticipants 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. |
Who may qualify
- Ages
- 4 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (18 listed)
- 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:
- 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;
Key exclusion criteria (3 listed)
- 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;
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AdalimumabAlso: ABT-D2E7, HumiraAdalimumab by subcutaneous injection every other week (eow) | Biological | Adalimumab 0.4 mg/kg, Adalimumab 0.8 mg/kg |
| MethotrexateMethotrexate 0.1 mg/kg at Week 0 and up to 0.4 mg/kg per week (maximum dose of 25 mg/week) orally. | Drug | Methotrexate |
| Placebo to AdalimumabA single subcutaneous loading dose at Week 0 followed by eow dosing beginning at Week 1. | Biological | Methotrexate |
| Placebo to MethotrexateOrally once a week | Drug | Adalimumab 0.4 mg/kg, Adalimumab 0.8 mg/kg |
Primary outcome
Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI) 75 Response at Week 16
Time frame: Baseline and 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.
Percentage of Participants Achieving a Physician's Global Assessment of Disease Activity (PGA) of "Cleared" (0) or "Minimal" (1) at Week 16
Time frame: 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.
18 secondary outcomes
Percentage of Participants Who Achieved a PASI 90 Response at Week 16
Time frame: Baseline and Week 16
Percentage of Participants Who Achieved a PASI 100 Response at Week 16
Time frame: Baseline and Week 16
Change From Baseline in the Children's Dermatology Life Quality Index (CDLQI) Score at Week 16
Time frame: Baseline and Week 16
Change From Baseline in the Pediatric Quality of Life Inventory (PedsQL) Score at Week 16
Time frame: Baseline and Week 16
Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Upon Re-Treatment in Period C
Time frame: Period C, Week 16
Time to Loss of Disease Control for Participants Who Entered Period B
Time frame: Period B (36 weeks) and Period D (52 weeks)
Percentage of Participants Achieving a PGA of "Cleared" (0) or "Minimal" (1) Over Time
Time frame: Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Percentage of Participants Achieving a PGA of "Cleared" (0) Over Time
Time frame: Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Percentage of Participants Who Achieved a PASI 50 Response Over Time
Time frame: Baseline, Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Percentage of Participants Who Achieved a PASI 75 Response Over Time
Time frame: Baseline, Period A, Weeks 4, 8, and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Percentage of Participants Who Achieved a PASI 90 Response Over Time
Time frame: Baseline, Period A, Weeks 4, 8 and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Percentage of Participants Who Achieved a PASI 100 Response Over Time
Time frame: Baseline, Period A, Weeks 4, 8, and 11, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Percent Change From Baseline in PASI Score Over Time
Time frame: Baseline, Period A, Weeks 4, 8, 11 and 16, Period C, Weeks 0 and 16, Period D, Weeks 0, 16, 28, 40 and 52
Change From Baseline in CDLQI Over Time
Time frame: Baseline, Period A, Weeks 4, and 8, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52
Percentage of Participants With CDLQI = 0 Over Time
Time frame: Period A, Weeks 4, 8 and 16, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52
Time to PASI 50/75/90/100 Response in Period A
Time frame: Period A, 16 weeks
Change From Baseline in PedsQL Over Time
Time frame: Baseline, Period A, Weeks 4 and 8, Period C, Weeks 0 and 4, Period D, Weeks 0, 11, 28, and 52
Change From Baseline in the Children's Depression Inventory: Short (CDI:S)
Time frame: Baseline, Period A, Weeks 4, 8, and 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28478975Papp 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.
- Derived from this study: PubMed 30054164Horneff 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.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
David A Williams, MD study director
AbbVie
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Adalimumab and Methotrexate in people with Plaque Psoriasis, run by AbbVie (prior sponsor, Abbott).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Who Achieved a Psoriasis Area and Severity Index (PASI) 75 Response at Week 16 (time frame: Baseline and Week 16). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01251614, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2017.