Clinical Trials Register

Summary
EudraCT Number:	2017-004021-33
Sponsor's Protocol Code Number:	ANB019-002
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2017-12-20
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

UK - MHRA

A.2

EudraCT number

2017-004021-33

A.3

Full title of the trial

A Single Arm Multiple Dose Study to Assess the Efficacy and Safety of ANB019 in Subjects with Generalized Pustular Psoriasis

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

To Assess the Efficacy and Safety of ANB019 in Subjects with Generalized Pustular Psoriasis

A.3.2

Name or abbreviated title of the trial where available

ANB019-002 - Generalized Pustular Psoriasis

A.4.1

Sponsor's protocol code number

ANB019-002

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03619902

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	AnaptysBio Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AnaptysBio Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	AnaptysBio Inc
B.5.2	Functional name of contact point	AnaptysBio Clinical Trials Info
B.5.3	Address:
B.5.3.1	Street Address	Suite 200, 10421 Pacific Center Court
B.5.3.2	Town/ city	San Diego, California
B.5.3.3	Post code	CA 92121
B.5.3.4	Country	United States
B.5.4	Telephone number	001 858 3626387
B.5.6	E-mail	clinicaltrialinfo@anaptysbio.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.2	Product code	ANB019
D.3.4	Pharmaceutical form	Solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	anti-IL-36R monoclonal antibody
D.3.9.2	Current sponsor code	ANB019
D.3.9.3	Other descriptive name	Alvarez 2
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	750
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

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

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

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

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

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

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

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1