E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Generalized Pustular Psoriasis (GPP) |
|
E.1.1.1 | Medical condition in easily understood language |
Psoriasis is a rare, severe, potentially life-threatening systemic inflammatory disease causing wide spread sterile pustules on the skin |
|
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 | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10037159 |
E.1.2 | Term | Psoriasis pustular |
E.1.2 | System Organ Class | 100000004858 |
|
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 |
To evaluate the efficacy of ANB019 in subjects with active GPP as measured by the Clinical Global Impression (CGI) scale according to the modified Japanese Dermatology Association (JDA) severity index total score.
To assess the safety and tolerability of ANB019 in subjects with GPP. |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the effect of ANB019 on the total and individual skin lesion symptoms as measured by the modified JDA severity index score. • To evaluate the effect of ANB019 on total and individual components of systemic manifestations and laboratory findings as measured by modified JDA severity index score. • To evaluate the effect of ANB019 on GPP using the GPPPGA • To assess the effect of ANB019 on the subject’s quality of life. • To determine any treatment effect of ANB019 in plaque psoriasis (if present) as measured by Psoriasis Area Severity Index (PASI). • To describe the pharmacokinetics (PK) of ANB019 in GPP subjects. • To test for immunogenicity to ANB019 |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male and female subjects must be 18 to 75 years of age inclusive, at the time of signing the informed consent. 2. Have clinically confirmed diagnosis of active GPP. 3. Have a Japanese Dermatology Association severity index total score of >6 and must be present with active pustules and erythema accounting for at least 10% of BSA or have a GPPPGA score of at least moderate severity. 4. Must be candidates for systemic therapy or phototherapy as assessed by the Investigator. 5. Meet the following laboratory screening criteria: a) Hemoglobin ≥90 g/L (≥9 g/dL) b) White blood cell count ≥3.0 × 109/L (≥3.0 × 103/μL) c) Platelets ≥100 × 109/L (≥100 × 103/μL) d) Serum creatinine <132.6 μmol/L (<1.5 mg/dL) e) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels ≤1.5 × upper limit of normal (ULN), f) Total bilirubin ≤1.5 × ULN. Subjects with known Gilbert’s disease who have a serum bilirubin less than <3 × ULN may be enrolled 6. Body mass index (BMI) of 18 to 36 kg/m2, inclusive, {BMI = weight (kg)/[height (m)]2}, and total body weight > 50 kg (110 lb). 7. Subjects must be otherwise in a good health as judged by the Investigator based on medical history, physical examination, ECG, hematology, and chemistry laboratory parameters, and urinalysis. 8. Contraception and pregnancy: a) A male subject must agree to use contraception during the treatment period and for at least 220 days (which includes the duration of relevant exposure plus the duration of sperm cycle) after the study treatment and refrain from donating sperm during this period. b) Female subjects: A female subject is eligible to participate if she has a negative serum pregnancy test (beta-human chorionic gonadotropin) at screening and a negative urine pregnancy test at Baseline, is not breastfeeding, and at least 1 of the following conditions apply: i) Not a woman of childbearing potential (WOCBP). OR ii) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 6 months after receiving the study treatment and refrain from donating oocytes for assisted reproduction during this period. The female subject’s selected form of contraception must be effective by the time the female subject enters into the study (eg, hormonal contraception should be initiated at least 28 days before Day 1). 9. Capable of giving signed informed consent as described, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. |
|
E.4 | Principal exclusion criteria |
1. Have other forms of psoriasis (eg, guttate) except plaque psoriasis. 2. Have concomitant dermatological (eg, subcorneal pustular dermatosis, impetigo herpetiformis, acute generalized exanthematous pustulosis) or medical conditions which may interfere with the Investigator’s ability to evaluate the subject’s response to therapy. 3. Have a history of clinically significant (as determined by the Investigator) cardiac, pulmonary, neurologic, gastrointestinal, endocrine, hematological, renal, hepatic, cerebral or psychiatric disease, or other major uncontrolled disease (a poorly controlled medical condition, such as but not limited to, poorly controlled diabetes, unstable ischemic heart disease, uncontrolled hypertension (systolic ≥160 mmHg and/or diastolic ≥95 mmHg based on the average of 2 blood tension measurements), and moderate to severe heart failure [New York Heart Association class III/IV]). 4. History of chronic or recurrent infectious disease, including but not limited to chest infection (eg, sinusitis, bronchitis, and bronchiectasis), urinary tract infection (eg, recurrent pyelonephritis), and skin infection (eg, abscesses, infected skin wounds, or ulcers) within 24 months prior to Screening. 5. History of a serious infection (eg, hepatitis, pneumonia) that led to hospitalization or treatment with IV antibiotics or antiviral treatment for an infection within 3 months prior to Screening or any recent infection requiring systemic antibiotic or systemic antiviral treatment within 4 weeks of Baseline. 6. History or any evidence of active infection within 4 weeks of Baseline (eg, bronchopulmonary, urinary, or gastrointestinal). 7. Presence of any factors that would predispose the subject to develop infection, eg, rectal fissures, poor dentition. 8. History of an opportunistic infection (eg, Pneumocystis carinii, aspergillosis, or mycobacteria other than tuberculosis [TB]), parasitic infections such as, but not exclusively, helminths, protozoa, Trypanosoma cruzi within 6 months of screening. 9. History of a herpes zoster infection within 2 months prior to screening. 10. Known or suspected autoimmune disorder, including but not limited to rheumatoid arthritis, fibromyalgia, systemic lupus erythematosus, polymyalgia rheumatica, giant cell arteritis, Behcet’s disease, dermatomyositis, multiple sclerosis, moderate to severe asthma, or other severe forms of atopy, any autoimmune vasculitis, autoimmune hepatitis, or any other active autoimmune disease for which a subject requires medical follow-up or medical treatment. 11. Any history of known or suspected congenital or acquired immunodeficiency state or condition that would compromise the subject’s immune status (eg, history of splenectomy). 12. Any major surgery within 4 weeks of study drug administration. 13. Malignancy or history of malignancy within 5 years, except for treated basal cell or squamous cell in situ carcinomas of the skin or squamous cell carcinomas deemed by the Principle Investigator to be fully treated. 14. History of any significant drug allergy or reaction (such as anaphylaxis or hepatotoxicity) and reactivity to polysorbate 20, a component of ANB019 formulation, or the inactive ingredients (excipients). Have taken the following drugs within the specified period prior to Screening or: a) Baseline: Topical medication (including corticosteroid, retinoids or vitamin A or D analog preparations, tacrolimus, calcineurin inhibitor, topical H1 and H2 antihistamines, tar preparations, topical antimicrobials, other medicated topical agents) or herbal preparation within 2 weeks prior to Baseline. b) Systemic therapy including but not limited to cyclosporine, methotrexate, acitretin, alitretinoin, fumaric acid esters, corticosteroids or any other immunosuppressant or immunomodulation drugs within 4 weeks prior to Baseline.A tapering washout of systemic therapies (e.g. cyclosporine, methotrexate, retinoids) can be used and the study drug can be introduced before the end of the washout period. c) Phototherapy ie, ultraviolet light B and photochemotherapy (eg, psoralen and ultraviolet A [PUVA]) within 4 weeks prior to Baseline. d) Previous treatment with anti-tumor necrosis factor/interleukin (IL-12/IL-23) and IL-17 or any other monoclonal antibodies is not allowed within 3 months or 5 half-lives or twice the duration of the biological effect of the product prior to Baseline. e) Live attenuated vaccine within 12 weeks of screening and during the study. f) Any investigational drug within 4 weeks or 5 half-lives, whichever is longer, of screening. g) Antibiotic or antiviral medication within 4 weeks of Baseline. 15. Topical bland emollients (without pharmacological active ingredients) for pustular psoriasis are allowed during the study, except within 24 hours prior to the study visits. Rescue medication will be directed by the Investigator as needed.
Due to space restriction please refer to protocol for other exclusion criteria |
|
E.5 End points |
E.5.1 | Primary end point(s) |
• Proportion of subjects achieving clinical response at Week 4 and Week 16. Clinical response is defined as “Very much improved”, “Much improved”, and “Minimally improved” on CGI scale according to modified JDA severity index total score. • Assessment of AEs. • Potentially significant and clinically important AEs, AESI, SAEs and AEs leading to withdrawal. • Physical examinations • Vital signs • 12-lead ECG • Clinical safety laboratory tests (hematology, biochemistry, and urinalysis). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Primary endpoint is assessed at week 4 and 16 |
|
E.5.2 | Secondary end point(s) |
• Change in modified JDA severity index total skin lesions score (sum of erythema, erythema with pustules, edema) at all study visits. • Change in affected BSA of erythema with pustules, erythema, and edema as measured by modified JDA severity index at all study visits. • Change in total and individual scores in systemic manifestations and laboratory findings as measured by modified JDA severity index at all study visits • GPPPGA score at each postbaseline visit will be analyzed for the proportion of subjects achieving a score of 0 or 1 at all study visits • GPPPGA change from Baseline scores at all study visits. • Change in Dermatology Life Quality Index (DLQI) total score at all study visits • Change in PASI score to evaluate a subject’s overall PP disease state if present at all study visits • Serum concentration following ANB019 administration. Following first dose administration of ANB019 these parameters will be determined: • AUC and other parameters as appropriate. • Presence of anti-drug antibodies (ADA).
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary endpoints are assessed at all visits |
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | No |
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 |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
|
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 | 1 |
E.8.9.1 | In the Member State concerned days | 2 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 2 |