Efficacy and Safety of Namilumab (MT203) for Plaque Psoriasis

Plaque Psoriasis Clinical Trial

Official title:

A Multi-Centre, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding and Proof of Concept Study, to Assess the Efficacy, Safety and Tolerability, Pharmacokinetics and Pharmacodynamics of Namilumab/MT203 At 4 Different Subcutaneous Doses in Subjects With Moderate to Severe Chronic Plaque Psoriasis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02129777
• Other study ID #: M1-1188_203
• Secondary ID: U1111-1146-12192
• Status: Completed
• Phase: Phase 2
• First received: April 14, 2014
• Last updated: August 26, 2016
• Start date: June 2014
• Est. completion date: February 2016

Study information

• Verified date: August 2016
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Canada: Biologics and Genetic Therapies Directorate, Health CanadaDenmark: Danish Medicines AgencyGermany: Federal Institute for Vaccines and BiomedicinesLatvia: State Agency of MedicinesPoland: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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

Description:

The drug being tested in this study is called namilumab. Namilumab is being tested to prove its effectiveness in treating moderate to severe chronic plaque psoriasis. This study will look at improvement of plaque psoriasis in people who take namilumab.

The study will enroll approximately 120 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the five treatment groups—which will remain undisclosed to the patient and study doctor during the study (unless there is 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 will consist of two parts. Eligible participants will receive 10 weeks of treatment with double-blinded study medication in a dose-finding and proof-of-concept investigation, followed by an extended treatment period (intended to be 52 weeks) with open-label study medication. At Week 12 participants will be assessed for primary endpoint response, which will determine the course of their progression through the open-label treatment period. Participants who show ≥ 75% reduction of Baseline (Day 1) Psoriasis Area and Symptoms Index (PASI) at Week 12, "Responders", will begin a washout interval (for a maximum of 24 weeks) with no use of study medication: this interval will continue until a partial loss of response is recorded (defined as ≥ 25% increase in PASI score over that recorded at Week 12) in assessments conducted on a 2-weekly basis - thereby prompting the start of dosing with open-label (OL) study medication (Week 0 OL through Week 52 OL). In contrast, participants who do not show ≥ 75% reduction of Baseline PASI at Week 12, "Partial/Non-Responders", will begin the open-label extension period 4 weeks after the final dose of blinded study medication.

Participants will then be followed-up through an 18-week post-treatment assessment period. During the open-label extension period participants will begin dosing with 80 mg namilumab; however, if an inadequate treatment response is recorded, then dose escalation to 150 mg namilumab will be implemented. Open-label study medication will be administered subcutaneously at 4 week intervals.

This multi-centre trial will be conducted in North America and Europe. The overall time to participate in the double-blind period of this study is up to 34 weeks The overall time to participate in the open-label period is 70 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: February 2016
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Is male or female aged 18 to 70 years, inclusive.

2. Is suffering from active but clinically stable plaque psoriasis (for at least 12 months) involving =10% of their body surface area andPsoriasis Area and Severity Index (PASI) score =12.

3. Must have been a candidate for, or have received, =1 phototherapy or systemic psoriasis therapy.

4. 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 and for 12 weeks after last dose of study medication.

5. 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 and for 12 weeks after last dose of study medication.

6. In the opinion of the investigator, is capable of understanding and complying with protocol requirements.

7. 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:

1. Has received any investigational agent during an interval equivalent to 5 half- lives for that agent prior to the study Baseline clinic visit, or is participating / plans to participate in any other clinical trial during this study.

2. 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.

3. Is required to take excluded medications.

4. Has a history of hypersensitivity or allergies to namilumab or any of the contents of the formulation.

5. Has other forms of psoriasis (eg drug-induced psoriasis, pustular, erythrodermic, exfoliative, inverse and/or guttate psoriasis).

6. 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.

7. 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.

8. 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 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.

9. 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).

10. 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.

11. 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 weeks prior to the Baseline clinic visit.

12. 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.

13. History of methotrexate treatment-associated lung toxicity.

14. 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.

15. 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.

16. Has an underlying condition that predisposes to infections (eg immunodeficiency, history of poorly controlled diabetes, splenectomy).

17. 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.

18. 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.

19. Has, in the judgment of the investigator, clinically significant abnormal clinical laboratory parameters at Screening.

20. 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.

21. Any other condition that, in the judgment of the investigator, might cause this study to be detrimental to the participant's health.

22. If female, is (a) pregnant / lactating / intending to become pregnant before or within the period of 12 weeks immediately after receiving the last dose of study medication; (b) intending to donate ova during this time period.

23. Intends to donate sperm during the course of this study or within a period of 12 weeks after receiving the last dose of study medication.

24. 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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Plaque Psoriasis
• Psoriasis

Intervention

Drug:
• Namilumab
Namilumab subcutaneous injection
• Placebo
Placebo subcutaneous injection

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants achieving an improvement in Psoriasis Area and Severity Index (PASI) score (reduction by = 75%) from Baseline to week 12	PASI is an index used to express the severity of psoriasis: it combines estimates on the severity of three features (erythema, induration and desquamation) and affected area of skin in each of four regions of the body (head/neck, arms/hands, chest/abdomen/back and buttocks/legs). Within each body region the area of skin involved is attributed a score from 0 - 6 (increasing involvement), and severity of the three clinical features rated on a scale from 0 to 4 (none to maximum) respectively. The total score ranges from 0 to 74 with higher scores indicating higher levels of disease. PASI75 denotes a 75% reduction of the PASI score from Baseline.	Baseline and Week 12	No
Secondary	Percentage of participants achieving an improvement in Psoriasis Area and Severity Index (PASI) scores = 75%, assessed at each post-Baseline visit	PASI is an index used to express the severity of psoriasis: it combines estimates on the severity of three features (erythema, induration and desquamation) and affected area of skin in each of four regions of the body (head/neck, arms/hands, chest/abdomen/back and buttocks/legs). Within each body region the area of skin involved is attributed a score from 0 - 6 (increasing involvement), and severity of the three clinical features rated on a scale from 0 to 4 (none to maximum) respectively. The total score ranges from 0 to 74, with higher scores indicating higher disease levels. PASI75 denotes a 75% reduction of the PASI score from Baseline.	Baseline and up to Week 10	No
Secondary	Change from Baseline in PASI score, assessed at all post-baseline visits	PASI is an index used to express the severity of psoriasis: it combines estimates on the severity of three features (erythema, induration and desquamation) and affected area of skin in each of four regions of the body (head/neck, arms/hands, chest/abdomen/back and buttocks/legs). Within each body region the area of skin involved is attributed a score from 0 - 6 (increasing involvement), and severity of the three clinical features rated on a scale from 0 to 4 (none to maximum) respectively. The total score ranges from 0 to 74, with higher scores indicating higher disease levels.	Baseline and up to Week 12	No
Secondary	Percentage of participants achieving an improvement in Psoriasis Area and Severity Index (PASI) scores = 50% assessed at each post-Baseline visit	PASI is an index used to express the severity of psoriasis: it combines estimates on the severity of three features (erythema, induration and desquamation) and affected area of skin in each of four regions of the body (head/neck, arms/hands, chest/abdomen/back and buttocks/legs). Within each body region the area of skin involved is attributed a score from 0 - 6 (increasing involvement), and severity of the three clinical features rated on a scale from 0 to 4 (none to maximum) respectively. The total score ranges from 0 to 74 with higher scores indicating higher disease activity. PASI50 denotes a 50% reduction of the PASI score from Baseline.	Baseline and up to Week 12	No
Secondary	Percentage of participants achieving an improvement in Psoriasis Area and Severity Index (PASI) scores = 90% at each post-Bseline visit assessed	PASI is an index used to express the severity of psoriasis: it combines estimates on the severity of three features (erythema, induration and desquamation) and affected area of skin in each of four regions of the body (head/neck, arms/hands, chest/abdomen/back and buttocks/legs). Within each body region the area of skin involved is attributed a score from 0 - 6 (increasing involvement), and severity of the three clinical features rated on a scale from 0 to 4 (none to maximum) respectively. The total score ranges form 0 to 74 with higher scores indicating higher levels of disease. PASI90 denotes a 90% reduction of the PASI score from Baseline.	Baseline and up to Week 12	No
Secondary	Proportion of participants achieving = 2 point improvement in static Physicians Global Assessment (sPGA) score, assessed (using a 6-point rating scale with range 0 = Clear to 5 = very severe) at all applicable post-Baseline visits	sPGA scoring determines psoriasis severity at a single point in time (based on erythema, plaque elevation and skin scaling for all lesions), assessed using a 6-point rating scale ranging from 0 = clear to 5 = very severe. A score of 0 or 1 indicates clear or almost clear/minimal.	Baseline and up to Week 12Baseline and up to Week 12	No
Secondary	Proportion of participants achieving Physicians Global Assessment (sPGA) clear or almost clear/minimal (sPGA = 0 or 1 using the 6-point rating scale with range 0 = Clear to 5 = Very severe), assessed at all applicable post-Baseline visits	sPGA scoring determines psoriasis severity at a single point in time (based on erythema, plaque elevation and skin scaling for all lesions), assessed using a 6-point rating scale ranging from 0 = clear to 5 = very severe. A score of 0 or 1 indicates clear or almost clear/minimal.	Baseline and up to Week 12	No
Secondary	Mean change from Baseline in sPGA score, assessed (using a 6-point rating scale with range 0 = Clear to 5 = Very Severe) at all applicable post-baseline visits	sPGA scoring determines psoriasis severity at a single point in time (based on erythema, plaque elevation and skin scaling for all lesions), assessed using a 6-point rating scale ranging from 0 = clear to 5 = very severe. A score of 0 or 1 indicates clear or almost clear/minimal.	Baseline and up to Week 12	No
Secondary	Change from Baseline in affected body surface area (BSA), assessed at all applicable post-Baseline visits		Baseline and up to Week 12	No
Secondary	Change from Baseline in Visual Analogue Scale (VAS) Itching, assessed at all applicable post-Baseline visits	The change between itch intensity measured at Baseline and at each week assessed. Participants will be asked to indicate their level of itching by making a mark on a line from 0 mm on the left (indicating no itching) to 100 mm on the right (indicating unbearable itching).	Baseline and up to Week 12	No
Secondary	Change from Baseline in VAS joint pain, assessed at all applicable post-Baseline visits	The change between joint pain intensity measured at each week assessed and joint pain intensity at baseline. Participants will be asked to indicate their level of joint pain by making a mark on a line from 0 mm on the left (indicating no joint pain) to 100 mm on the right (indicating unbearable joint pain).	Baseline and up to Week 12	No
Secondary	Mean change from Baseline in VAS morning stiffness, assessed at all applicable post-Baseline visits	The change between morning stiffness measured at each week assessed and morning stiffness intensity at baseline. Participants will be asked to indicate their level of morning stiffness by making a mark on a line from 0 mm on the left (indicating no morning stiffness) to 100 mm on the right (indicating unbearable morning stiffness).	Baseline and up to Week 12	No
Secondary	Mean change from Baseline in VAS duration of morning stiffness, assessed at all applicable post-Baseline visits	The change between duration of morning stiffness measured at each week assessed and duration of morning stiffness at baseline. Participants will be asked to indicate duration morning stiffness in response to a standard question included in a portable electronic devise kept by the participant for the duration of the study.	Baseline and up to Week 12	No
Secondary	Change from Baseline in Dermatology Life Quality Index (DLQI) score	The DQLI is a 10 item questionnaire to assess quality of life in patients with skin diseases. The scoring of each question is as follows: 3=Very much; 2=A lot; 1=A little; 0=Not at all. The DLQI 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	Baseline and at Weeks 12 and week 22	No
Secondary	Change in score from Baseline in Short Form 36 Health Survey (SF-36)	The SF-36 measures the impact of disease on overall quality of life and consists of 36 questions in eight domains (physical function, pain, general and mental health, vitality, social function, physical and emotional health). The individual domain scores are calculated and transformed to range from 0 to 100, with higher scores indicating a better level of functioning. A positive change from baseline score indicates an improvement.	Baseline and at Week 12 and Week 22	No
Secondary	• Change in score from Baseline in EuroQoL Health Questionnaire (EQ-5D)	The EuroQoL Questionnaire-5 Dimension (EQ-5D) 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 mood. The score ranges 0-100. The higher score indicates a better health state perceived by the participant.	Baseline and at Weeks 12 and Week 22	No
Secondary	Change from Baseline for Nail Psoriasis Severity Index (NAPSI)	The nails are graded for nail matrix psoriasis and nail bed psoriasis. The sum of these two scores is the total score for that nail. Per nail, the NAPSI score ranges from 0 (no nail psoriasis) to 4 (most severe nail psoriasis).	Baseline and up to Week 12	No