| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
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| E.1.1.1 | Medical condition in easily understood language |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 18.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10071117 |
| E.1.2 | Term | Plaque psoriasis |
| E.1.2 | System Organ Class | 100000004858 |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The objective of Part 1 of the study is to compare the efficacy and safety of CHS-0214 and European sourced Enbrel (Enbrel EU) 50 mg given twice weekly for 12 weeks.
The objective of Part 2 of the study is to compare the safety and durability of response of CHS-0214 and Enbrel (EU), 50 mg given once a week from 13 weeks up to 47 weeks of treatment. Subjects who discontinue study drug prior to week 47 will be seen for a follow-up visit 28 days after the last dose of study drug. Subjects who complete 47 weeks of study drug will be seen at week 48 and again for a follow-up visit 28 days after the last dose of study drug is applicable. |
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| E.2.2 | Secondary objectives of the trial |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1.Male or female adult ≥ 18 years of age
2.Chronic PsO diagnosed at least 6 months prior to Screening
3.Moderate to severe chronic PsO as defined at Screening by:
•PASI score ≥12
•Physician’s Static Global Assessment (PSGA) score of ≥3 (based on a scale of 0-5)
•BSA affected by chronic PsO of ≥10%, and
•Dermatology Life Quality Index (DLQI) ≥10
4.Must be considered a candidate for starting biological DMARDs by the investigator. This includes patients who: a) have previously received at least one non-biologic systemic PsO therapy or one treatment/course of phototherapy. b) have a contraindication to non-biologic systemic psoriasis treatments or phototherapy. c) or for whom immediate biologic therapy is considered appropriate regardless of their prior treatment.
5.Must be naïve to all approved or unapproved systemic biologic therapies (other than insulin or hormones)
6.Able and willing to give written informed consent prior to performance of any study-related procedures
7.Women who meet one of the following:
a) Women of childbearing potential with a negative urine pregnancy test at Screening who agree to use 1 or more approved methods of birth control during the study. Approved methods of birth control are: hormonal contraception, intrauterine device; diaphragm plus spermicide; Abstinence from heterosexual intercourse will be acceptable only if it´s the preferred and usual lifestyle of the subject regardless of study participation, abstinence should be practiced for the duration of the study and until 3 weeks after taking the last dose of study drug.
b)Women who have been postmenopausal for at least 2 years (with amenorrhea for at least one year) or have had a hysterectomy, bilateral salpingo-oophorectomy, or tubal ligation prior to signing the informed consent form. |
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| E.4 | Principal exclusion criteria |
1. Forms of psoriasis other than chronic PsO (eg, pustular erythrodermic, guttate psoriasis);
2. Initiation of a drug that is known to cause or exacerbate psoriasis (including, but not limited to: beta-blockers, lithium, and anti-malarials), within the 6 months prior to Randomization (Week 0/Day 0). Subjects who have been on a stable dose for at least 6 months prior to Randomization without exacerbation of psoriasis may be enrolled and do not need to discontinue these medications;
3. Ongoing use of prohibited psoriasis treatments (eg, systemic corticosteroids, ultraviolet (UV) therapy, systemic therapy for PsO) these treatments should have been discontinued at least 4 weeks prior to Randomization;
4. Use of class 1-5 topical corticosteroids within 2 weeks prior to randomisation. Note: Use of mild (class 6-7) topical corticosteroids only on face, scalp, axillae, genitalia or groin and mild/bland moisturizers/lubricants may be used at any time during the study except within 24 hours prior to a screening PASI assessment or study visit;
5.Use of phosphodiesterase type 4 (PDE4) inhibitors (e.g., apremilast [Otezla]) within the 4 weeks prior to Randomization;
6. Subjects taking non-psoriatic concomitant medications should be on stable doses for at least 30 days prior to Randomization;
7. Administration of a live vaccine within 4 weks prior to screening
8. Participation in an Investigational drug or device study within the 30 days prior to Randomization or a period equal to 5 times the half-life of the investigational agent, whichever is longer;
9. History of alcohol or drug abuse within 2 years prior to Screening;
10. Diagnosis of rheumatic disease, autoimmune disease, connective tissue disease, or immune deficiency disease (e.g., primary Sjögren’s syndrome, systemic lupus erythematosus, and demyelinating diseases such as multiple sclerosis);
11. White blood cell count <3500 cells/mm3, lymphocyte count <1000 cells/mm3, platelet count ≤125,000 cells/mm3, serum creatinine ≥2 mg/dL (177 µmol/L), alanine transaminase or aspartate transaminase ≥2 × the upper limit of normal, or hemoglobin ≤8.5 g/dL at Screening;
12. Presence or history of malignancy, except for successfully treated non metastatic basal or squamous cell carcinoma of the skin and carcinoma in situ of the cervix;
13. Presence of tuberculosis (TB) based on positive blood test (QuantiFERON® TB Gold test) during Screening or subjects with known exposure to a patient with active TB; Note: QuantiFERON-TB Gold test can be repeated one time using a fresh sample in subjects with an indeterminate result or low positively defined as Quantiferon TB Antigens minus Nil value = 0.35 - IU/mL, if the repeat test result is negative the subject may participate in the study. If the repeat test result is indeterminate or positive the subject does not qualify for the study.
14. History of positive test results for fungal or other infections (e.g., histoplasmosis, coccidiomycosis) required by regional guidelines within 3 months prior to Randomization (Week 0/Day 0);
15. Abnormal chest X-ray within 6M prior randomization demonstrating active lung disease processes ( eg evidence of TB or another active disease process) if a chest X-ray has not been obtained withing the past 6M one should be obtained during the screening process;
16. Major systemic infections, including human immunodeficiency virus (HIV);
17. Unresolved Hepatitis B or Hepatitis C infection (defined as positive hepatitis B surface antigen [HBsAg], hepatitis B core antibody [HBcAb], or hepatitis C virus [HCV]);
18. Class III or IC congestive heart failure (as defined by the New York Heart Association) (NY Heart Association) (New York Heart Association, 1994)
19. Presence of any significant comorbid medical condition(s), including, but not limited to:
a) Uncontrolled diabetes mellitus (Hemoglobin A1C [HgbA1c] 8% within the 3 months prior to Screening or history of diabetic ketoacidosis or hypoglycemic reactions requiring hospitalization within the 12 months prior to Screening),
b) Uncontrolled hypertension (systolic blood pressure >160 mmHg and diastolic blood pressure >100 mmHg) (Mancia, 2013) within the 3 months prior to Screening,
c) Severe kidney disease requiring hemodialysis or peritoneal dialysis,
d) Advanced liver disease, such as liver cirrhosis,
e) Severe congestive heart failure or history of ejection fraction 30%,
f) Severe lung disease requiring home oxygen,
g) Active unstable angina requiring daily treatment with nitrates or other medications;
20. Presence of any other major medical or psychiatric illness that in the opinion of the Investigator would put the subject at increased risk or affect the ability to participate in the study;
21. Known or suspected sensitivity or allergic reactions to latex or latex containing products; or
22. Women who are pregnant or nursing.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
Efficacy endpoints:
In order to meet the regulatory requirements of different regions the study will have 2 different primary efficacy endpoints:
1. Mean percent change in PASI from baseline (first dose of study drug) at week 12. This will be the primary endpoint supporting a marketing authorisation application (MAA) in the European Union (EU)
2. Proportion of subjects achieving a PASI-75 from Baseline at Week 12. This Endpoint is intended to support a biologics licensing application (BLA) in the US. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
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| E.5.2 | Secondary end point(s) |
The secondary efficacy endpoints include:
•Mean percent change in PASI from Baseline at Weeks 4, 8, 24, 36, and 48;
•The proportion of subjects who achieve PASI-75 from Baseline at Weeks 4, 8, 24, 36, and 48;
•The proportion number of subjects who achieve a 50% improvement in Psoriasis Area and Severity Index (PASI-50) and a 90% improvement in Psoriasis Area and Severity Index (PASI-90) response rates from Baseline at Weeks 4, 8, 12, 24, 36, and 48;
•Change in PSGA of disease activity at Baseline to Weeks 4, 8, 12, 24, 36, and 48, and at the Follow-up Visit;
•The proportion of subjects with a change in PSGA = 0-1, demonstrating clear or almost clear skin at Weeks 4, 8, 12, 24, 36, and 48
•Change in Subject’s Global Assessment (SGA) of Psoriasis from Baseline to Weeks 4, 8, 12, 24, 36, and 48;
•Number of subjects with PSGA indicative of clear or almost clear (score 0-1) at Weeks, 4, 8, 12, 24, 36, and 48;
•Change in DLQI from Baseline to Weeks 12, 24, and 48;
•Change in EuroQol 5-Dimension Health Status Questionnaire from Baseline to Weeks 12, 24, and 48;
•Change in Health Assessment Questionnaire-Disability Index (HAQ-DI) from Baseline to Weeks 12, 24, and 48 for subjects with concurrent PsA only; and
•Change in highly sensitive C-reactive protein (hs CRP mg/L) from Baseline to Weeks 12, 24, and 48 for subjects with PsA only.
Safety endpoints: Safety will be assessed by evaluating the incidence of and reasons for subject discontinuations, treatment emergent adverse events, ISRs, changes in safety laboratory parameters, vital signs, physical examinations, and electrocardiogram findings. In addition, subjects will be monitored for TB with regular QuantiFERON-TB Gold test (every 6 months or more frequently for regions with a high incidence of TB, or to evaluate signs and symptoms that might be due to TB). |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. week 4-8-24-36-48
2. week 4-8-24-36-48
3. week 4-8-12-24-36-48
4. week 4-8-12-24-36-48
5. week 4-8-12-24-36-48
6. week 4-8-12-24-36-48
7. week 4-8-12-24-36-48
8. Weeks 12, 24, and 48
9. Weeks 12, 24, and 48
10. Weeks 12, 24, and 48
11. Weeks 12, 24, and 48
12. Continuous |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Australia |
| Canada |
| Chile |
| Germany |
| Israel |
| Poland |
| Russian Federation |
| South Africa |
| United Kingdom |
| United States |
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| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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