Efficacy and Safety of Namilumab (MT203) for Plaque Psoriasis

Phase 2

Completed

Conditions: Plaque Psoriasis

Interventions: Drug: Namilumab
Drug: Placebo

Registration Number: NCT02129777

Lead Sponsor: Takeda

Brief Summary: The purpose of this study is to establish proof of efficacy for namilumab in moderate to severe plaque psoriasis, measured as Psoriasis Area and Severity Index (PASI)75 response rate at Week 12.

Detailed Description: The drug tested in this study is called namilumab. Namilumab was tested to prove its effectiveness in treating moderate to severe chronic plaque psoriasis. This study looked at improvement of plaque psoriasis in participants who take namilumab.

The study enrolled 122 participants. Participants were randomly assigned (by chance, like flipping a coin) to one of five treatment groups that were undisclosed to the patient and study doctor during the study (unless there was an urgent medical need):

* Namilumab subcutaneous injection 300 mg Day 1, 150 mg Days 15, 43 and 71

* Namilumab subcutaneous injection 160 mg Day 1, 80 mg Days 15, 43 and 71

* Namilumab subcutaneous injection 100 mg Day 1, 50 mg Days 15, 43 and 71

* Namilumab subcutaneous injection 40 mg Day 1, 20 mg Days 15, 43 and 71

* Placebo (dummy inactive subcutaneous injection) - this is a liquid solution that looks like the study drug but has no active ingredient Days 1, 15, 43 and 71.

This study consisted of two parts. Eligible participants received 10 weeks of treatment with double-blinded study medication, followed by an extended treatment period (active extension period, intended to be 52 weeks) with open-label study medication. At Week 12, participants were assessed for primary endpoint response, which determined the course of their progression through the open-label treatment period. Participants who showed \>=75% reduction of Baseline (Day 1) PASI at Week 12, "Responders", began a washout interval (for a maximum of 24 weeks) with no use of study medication: this interval continued until a partial (25%) loss of Week 12 treatment response is recorded in assessments conducted on a 2-weekly basis - thereby prompting the start of dosing with open-label (OL) study medication (Day 0 OL through Week 52 OL). In contrast, participants who did not show \>=75% reduction of Baseline PASI score at Week 12, "Partial/Non-Responders", began the open-label extension period 4 weeks after the final dose of blinded study medication.

Participants were then followed-up through an 18-week post-treatment assessment period during which no medication was given. During the open-label extension period participants began dosing with 80 mg namilumab; however, if an inadequate treatment response was recorded, then dose escalation to 150 mg namilumab was implemented.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 122

Inclusion Criteria

Is male or female aged 18 to 70 years, inclusive.
Is suffering from active but clinically stable plaque psoriasis (for at least 6 months) involving >=10% of their body surface area and Psoriasis Area and Severity Index (PASI) score >=12.
Must have been a candidate for, or have received, >= phototherapy or systemic psoriasis therapy.
A male participant who is non-sterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of the informed consent throughout the duration of the study (including the treatment period and 18 weeks after last dose of study medication).
A female participant of childbearing potential who is sexually active with a non-sterilized male partner agrees to routinely use adequate contraception from signing of the informed consent throughout the duration of the study (including the treatment period and 18 weeks after last dose of study medication).
In the opinion of the investigator, is capable of understanding and complying with protocol requirements.
The participant or, when applicable, the participant's legally acceptable representative signs and dates a written informed consent form and any required privacy authorization prior to the initiation of any study procedures.

Exclusion Criteria

Has received any investigational agent during an interval equivalent to 5 half- lives for that agent agent - or an interval of 30 days if longer - prior to the study Baseline clinic visit, or is participating / plans to participate in any other clinical trial during this study.
Has received namilumab, any other Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) / GM-CSF receptor or granulocyte stimulating factor (G-GSF) signaling inhibitor either in a previous clinical study or as a therapeutic agent.
Is required to take excluded medications.
Has a history of hypersensitivity or allergies to namilumab or any of the contents of the formulation.
Has other forms of psoriasis (eg drug-induced psoriasis, pustular, erythrodermic, exfoliative, inverse and/or guttate psoriasis).
Evidence of skin conditions other than psoriasis (eg, eczema) at the time of the Screening clinic visit, or between the Screening visit and study drug initiation, that would interfere with evaluations of the effect of investigational product on psoriasis.
Has a history or evidence of a clinically significant disorder (including but not limited to cardiopulmonary, oncologic, renal, metabolic, hematologic or psychiatric), condition or disease that, in the opinion of the investigator and Takeda physician would pose a risk to participant safety or interfere with the study evaluation, procedures or completion.
Evidence of clinically uncontrolled respiratory disease (including sarcoidosis) on the basis of data from the subjects' respiratory assessments - including chest X-ray, lung function tests (forced expiratory volume in one second [FEV1], forced vital capacity [FVC], peak expiratory flow rate [PEFR]) and pulse oximetry performed at Screening. The subjects must have saturation of peripheral oxygen (SpO2) ≥ 94%, FEV1 and/or FVC ≥ 60 % of predicted values at Screening and Baseline and no uncontrolled lung disease. Subject treatment initiated or modified to control lung disease within 24 weeks prior to Screening must be considered exclusionary.
History of clinically significant interstitial lung disease - e.g. chronic or recurrent pulmonary infection where macrophages are important for the clearance of the infection (such as Pneumocystis (carinii) jiroveci pneumonia, allergic bronchopulmonary aspergillosis, Nocardia infections, Actinomyces infection).
Presence or history of active tuberculosis (TB) or latent TB infection, where no anti-TB treatment has been given or where successful completion of an appropriate course of anti-TB therapy cannot be documented.
A positive QuantiFERON-TB Gold test and / or evidence of active or latent TB by chest X- ray, not accompanied by initiation of an approved regimen of anti-TB therapy at least 12 months prior to the Baseline clinic visit.
Has a history of severe chronic obstructive pulmonary disease (COPD) and / or history of severe COPD exacerbation(s), or a history of asthma with exacerbations requiring hospitalization, within the last 12 months prior to the Screening visit.
History of methotrexate treatment-associated lung toxicity.
Has a history of cancer within the last 10 years except for adequately managed basal cell or squamous cell carcinoma of the skin or in situ carcinoma of the cervix treated and considered cured.
Has a history of treatment with anti-cancer chemotherapy (e.g. alkylating agents, anti-metabolites, purine analogues) and/or monoclonal antibodies, or has received GM-CSF / G-CSF treatment associated with chemotherapy within the last 5 years.
Has an underlying condition that predisposes to infections (eg immunodeficiency, history of poorly controlled diabetes, splenectomy).
Has any clinically significant illness within 4 weeks prior to the first dose of study medication or during the study - including acute or chronic infectious disease, which may influence the outcome of the study.
Has a known history of infection with hepatitis B virus, hepatitis C virus, or human immunodeficiency virus (HIV), or has serological findings at the Screening visit which indicate active or latent hepatitis B, hepatitis C or HIV infection.
Has, in the judgment of the investigator, clinically significant abnormal clinical laboratory parameters at Screening including, but not limited to: Hemoglobin <8.5 g/dL, Neutrophils <1500/mm^3, Platelet count <75 000 cells/mm^3 and AST or ALT >2 x ULN.
Has a history of drug abuse (defined as any illicit drug use), or a history of alcohol abuse within 2 years prior to the Screening visit.
Any other condition that, in the judgment of the investigator, might cause this study to be detrimental to the participant's health.
If female, is (a) pregnant / lactating / intending to become pregnant before or within the period of 18 weeks immediately after receiving the last dose of study medication; (b) intending to donate ova during this time period.
Intends to donate sperm during the course of this study or within a period of 18 weeks after receiving the last dose of study medication.
Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee involved in conduct of this study (eg, spouse, parent, child, sibling), or may consent under duress.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Blinded period: Namilumab 160 mg + namilumab 80 mg	Namilumab	Namilumab 160 mg (2 separate injections of 80 mg), subcutaneous injection, on Day 1, followed by namilumab 80 mg subcutaneous injection, on Days 15, 43 and 71.
Blinded period: Placebo	Placebo	Placebo (2 separate injections), subcutaneous injection, on Day 1, followed by placebo, subcutaneous injection, on Days 15, 43 and 71.
Blinded period: Namilumab 100 mg + namilumab 50 mg	Namilumab	Namilumab 100 mg (2 separate injections of 50 mg), subcutaneous injection, on Day 1, followed by namilumab 50 mg subcutaneous injection, on Days 15, 43 and 71.
Open label: Namilumab 150 mg	Namilumab	Namilumab 150 mg, subcutaneous injection, from Week 8 and then every 4 weeks thereafter up to 52 weeks (active extension period) - if appropriate on the basis of treatment response.
Blinded period: Namilumab 40 mg + namilumab 20 mg	Namilumab	Namilumab 40 mg (2 separate injections of 20 mg), subcutaneous injection, on Day 1, followed by namilumab 20 mg subcutaneous injection, on Days 15, 43 and 71.
Open label: Namilumab 80 mg	Namilumab	Namilumab 80 mg subcutaneous injection, at Week 0 and every 4 weeks thereafter up to 52 weeks (active extension period) - if appropriate on the basis of treatment response.
Blinded period: Namilumab 300 mg + namilumab 150 mg	Namilumab	Namilumab 300 mg (2 separate injections of 150 mg), subcutaneous injection, on Day 1, followed by namilumab 150 mg subcutaneous injection, on Days 15, 43 and 71.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving 75 Percent Reduction From Baseline Psoriasis Area and Severity Index (PASI) Score (PASI75 Response) at Week 12	Week 12	PASI is an assessment of psoriasis lesion severity and affected body area combined into single score. The body was divided into 4 sections: head (h), trunk (t), upper (u) and lower (l) extremities. For each section, percent body surface area (A) involved was estimated: 0= No involvement to 6= 90-100 percent (%). Severity was estimated by clinical signs: erythema (E), induration (I), and desquamation (D); scale: 0= no symptoms to 4= very marked. Final PASI = 0.1(Eh + Ih + Dh)Ah + 0.3(Et + It + Dt)At + 0.2(Eu + Iu + Du)Au + 0.4(El + Il + Dl)Al where head: 0.1, upper extremities (arms): 0.2, trunk: 0.3, lower extremities (legs): 0.4 (corresponding to approximately 10%, 20%, 30%, and 40% of body surface area, respectively); total possible score range: 0= no disease to 72= maximal disease. Participants showing at least 75% reduction in PASI score relative to baseline PASI Score are reported.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in PASI Score at Weeks 2, 4, 6, 10, and 12	Baseline, Weeks 2, 4, 6, 10, and 12	PASI is an assessment of psoriasis lesion severity and affected body area combined into single score. The body was divided into 4 sections: head (h), trunk (t), upper (u) and lower (l) extremities. For each section, percent body surface area (A) involved was estimated: 0= No involvement to 6= 90-100 percent (%). Severity was estimated by clinical signs: erythema (E), induration (I), and desquamation (D); scale: 0= no symptoms to 4= very marked. Final PASI = 0.1(Eh + Ih + Dh)Ah + 0.3(Et + It + Dt)At + 0.2(Eu + Iu + Du)Au + 0.4(El + Il + Dl)Al where head: 0.1, upper extremities (arms): 0.2, trunk: 0.3, lower extremities (legs): 0.4 (corresponding to approximately 10%, 20%, 30%, and 40% of body surface area, respectively); total possible score range: 0= no disease to 72= maximal disease.
Change From Baseline in Affected Body Surface Area (BSA) at Weeks 2, 4, 6, 10, and 12	Baseline, Weeks 2, 4, 6, 10, and 12	Assessment of BSA with psoriasis was performed by means of the palm method, where the palm of the participant's hand represented 1% of BSA. The affected areas were then calculated by their size compared to the participant's palm.
Change From Baseline in Short Form 36 Health Survey (SF-36) at Week 12	Baseline, Week 12	SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects are summarized as physical and mental health summary scores. The score range for the physical and mental health scores is 0-100 (100=highest level of functioning).
Percentage of Participants Achieving 90 Percent Reduction From Baseline PASI Score (PASI90 Response) at Weeks 2, 4, 6, 10 and 12	Weeks 2, 4, 6, 10 and 12	PASI is an assessment of psoriasis lesion severity and affected body area combined into single score. The body was divided into 4 sections: head (h), trunk (t), upper (u) and lower (l) extremities. For each section, percent body surface area (A) involved was estimated: 0= No involvement to 6= 90-100 percent (%). Severity was estimated by clinical signs: erythema (E), induration (I), and desquamation (D); scale: 0= no symptoms to 4= very marked. Final PASI = 0.1(Eh + Ih + Dh)Ah + 0.3(Et + It + Dt)At + 0.2(Eu + Iu + Du)Au + 0.4(El + Il + Dl)Al where head: 0.1, upper extremities (arms): 0.2, trunk: 0.3, lower extremities (legs): 0.4 (corresponding to approximately 10%, 20%, 30%, and 40% of body surface area, respectively); total possible score range: 0= no disease to 72= maximal disease. Participants showing at least 90% reduction in PASI score relative to baseline PASI Score are reported.
Percentage of Participants Achieving Greater Than or Equal to (>=) 2 Point Improvement From Baseline in Static Physicians Global Assessment (sPGA) Score at Weeks 2, 4, 6, 10 and 12	Weeks 2, 4, 6, 10 and 12	sPGA for psoriasis is scored on a 6-point scale, reflecting a global consideration of the erythema, plaque elevation and skin scaling across all psoriatic lesions. sPGA of psoriasis scale ranges from 0 (clear) to 5 (very severe). Participants who had \>=2 point improvement are reported.
Percentage of Participants Achieving 75 Percent Reduction From Baseline PASI Score (PASI75 Response) at Weeks 2, 4, 6, and 10	Weeks 2, 4, 6 and 10	PASI is an assessment of psoriasis lesion severity and affected body area combined into single score. The body was divided into 4 sections: head (h), trunk (t), upper (u) and lower (l) extremities. For each section, percent body surface area (A) involved was estimated: 0= No involvement to 6= 90-100 percent (%). Severity was estimated by clinical signs: erythema (E), induration (I), and desquamation (D); scale: 0= no symptoms to 4= very marked. Final PASI = 0.1(Eh + Ih + Dh)Ah + 0.3(Et + It + Dt)At + 0.2(Eu + Iu + Du)Au + 0.4(El + Il + Dl)Al where head: 0.1, upper extremities (arms): 0.2, trunk: 0.3, lower extremities (legs): 0.4 (corresponding to approximately 10%, 20%, 30%, and 40% of body surface area, respectively); total possible score range: 0= no disease to 72= maximal disease. Participants showing at least 75% reduction in PASI score relative to baseline PASI Score are reported.
Change From Baseline in sPGA Score at Weeks 2, 4, 6, 10, and 12	Baseline, Weeks 2, 4, 6, 10, and 12	sPGA for psoriasis is scored on a 6-point scale, reflecting a global consideration of the erythema, plaque elevation and skin scaling across all psoriatic lesions. sPGA of psoriasis scale ranges from 0 (clear) to 5 (very severe).
Percentage of Participants Achieving 50 Percent Reduction From Baseline PASI Score (PASI50 Response) at Weeks 2, 4, 6, 10 and 12	Weeks 2, 4, 6, 10 and 12	PASI is an assessment of psoriasis lesion severity and affected body area combined into single score. The body was divided into 4 sections: head (h), trunk (t), upper (u) and lower (l) extremities. For each section, percent body surface area (A) involved was estimated: 0= No involvement to 6= 90-100 percent (%). Severity was estimated by clinical signs: erythema (E), induration (I), and desquamation (D); scale: 0= no symptoms to 4= very marked. Final PASI = 0.1(Eh + Ih + Dh)Ah + 0.3(Et + It + Dt)At + 0.2(Eu + Iu + Du)Au + 0.4(El + Il + Dl)Al where head: 0.1, upper extremities (arms): 0.2, trunk: 0.3, lower extremities (legs): 0.4 (corresponding to approximately 10%, 20%, 30%, and 40% of body surface area, respectively); total possible score range: 0= no disease to 72= maximal disease. Participants showing at least 50% reduction in PASI score relative to baseline PASI Score are reported.
Change From Baseline in VAS Morning Stiffness Score at Weeks 2, 4, 6, 10, and 12	Baseline, Weeks 2, 4, 6, 10, and 12	Assessments were performed using a portable electronic device, which was kept and used by the participant throughout the duration of the study. Participants were asked to indicate their level of morning stiffness by marking a horizontal line with "No stiffness" at the left extreme and "Very severe stiffness" at the right extreme (scale ranging from 0 - 10, but not shown on the line). Each assessment was intended to capture the severity of stiffness experienced by the participant since waking on that particular day.
Change From Baseline in Duration of Morning Stiffness at Weeks 2, 4, 6, 10, and 12	Baseline, Weeks 2, 4, 6, 10, and 12	Assessments were performed using a portable electronic device, which was kept and used by the participant throughout the duration of the study. Duration of stiffness was elicited in response to a standard question included in the portable device.
Change From Baseline in Visual Analogue Scale (VAS) Itching Score at Weeks 2, 4, 6, 10, and 12	Baseline, Weeks 2, 4, 6, 10, and 12	Assessments were performed using a portable electronic device, which was kept and used by the participant throughout the duration of the study. Participants were asked to indicate their level of itching by marking a horizontal line with "No itch" at the left extreme and "Worst itch imaginable" at the right extreme (scale ranging from 0 - 10, but not shown on the line). Each assessment was intended to capture the severity of itching experienced during the previous 24 hours.
Change From Baseline in EQ-5D-VAS Score at Week 12	Baseline, Week 12	EQ-5D-VAS is a participant rated questionnaire to assess health-related quality of life in terms of a single index value. The VAS component rates current health state on a scale from 0 mm ("Worst imaginable health state") to 100 mm ("Best imaginable health state"); higher scores indicate a better health state.
Mean Change From Baseline in Nail Psoriasis Severity Index (NAPSI) Score at Weeks 2, 4, 6, 10, and 12	Baseline, Weeks 2, 4, 6, 10, and 12	The NAPSI quantifies severity of nail psoriasis by evaluating the presence or absence of psoriatic manifestations on the nail matrix (pitting, leukonychia, red spots on lunula, crumbling) and nail bed (onycholysis, splinter hemorrhages, subungual hyperkeratosis, oil drop \[salmon patch dyschromia\]). Each finger nail divided with imaginary lines into quadrants and scored for both nail matrix and nail bed psoriasis (range from 0 \[absence of psoriasis\] to 4 \[presence of psoriasis in all 4 quadrants\]). The total NAPSI score equals the sum of scores for all of the finger nails evaluated and ranges from 0 to 80. Higher scores = more severe psoriasis.
Percentage of Participants Achieving a sPGA Response of Clear (0) or Almost Clear (1) at Weeks 2, 4, 6, 10 and 12	Weeks 2, 4, 6, 10 and 12	sPGA for psoriasis is scored on a 6-point scale, reflecting a global consideration of the erythema, plaque elevation and skin scaling across all psoriatic lesions. sPGA of psoriasis scale ranges from 0 (clear) to 5 (very severe). 'Clear' and 'Almost clear' included all participants who had scored a 0 or 1.
Change From Baseline in VAS Joint Pain Score at Weeks 2, 4, 6, 10, and 12	Baseline, Weeks 2, 4, 6, 10, and 12	Assessments were performed using a portable electronic device, which was kept and used by the participant throughout the duration of the study. Participants were asked to indicate their severity of joint pain by marking a horizontal line with "No pain" at the left extreme and "Worst pain imaginable" at the right extreme (scale ranging from 0 - 10, but not shown on the line). Each assessment was intended to capture the severity of pain experienced during the previous 24 hours.
Change From Baseline in EuroQoL Health Questionnaire (EQ-5D)- Index Score at Week 12	Baseline, Week 12	EQ-5D-Index score is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. The score ranges from -0.594 to 1.000. The higher score indicates a better health state perceived by the participant.
Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 12	Baseline, Week 12	The DLQI is a 10-point rating scale for determining the impact of dermatological conditions on the participant's quality of life (daily activities, personal relationships, symptoms and feelings, leisure, work and school, and treatment). Maximum total score is 30, where 0-1 represents "No effect at all on participant's life" and 21-30 "Extremely large effect on participant's life" - higher scores indicating poorer quality of life.