Clinical Trials Register

Summary
EudraCT Number:	2020-003143-28
Sponsor's Protocol Code Number:	BB-2293-101b
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:	2020-08-06
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

2020-003143-28

A.3

Full title of the trial

A First-in-Human, Double-Blind, Randomised, Vehicle Controlled Phase I/II Proof of Concept Study to Investigate the Safety, Tolerability, Pharmacokinetics and Efficacy of BEN2293 in Patients with Mild to Moderate Atopic Dermatitis (AD).

A.3.1

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

A First-in-Human trial to investigate how safe, tolerable, effective and how the body handles BEN2293 in patients who have mild to moderate eczema.

A.4.1

Sponsor's protocol code number

BB-2293-101b

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	BenevolentAI Bio Limited
B.1.3.4	Country	United Kingdom
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	BenevolentAI Bio Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	BenevolentAI Bio Limited
B.5.2	Functional name of contact point	Chief Medical Officer
B.5.3	Address:
B.5.3.1	Street Address	4-8 Maple Street
B.5.3.2	Town/ city	London
B.5.3.3	Post code	W1T 5HD
B.5.3.4	Country	United Kingdom
B.5.6	E-mail	leo.james@benevolent.ai

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	BEN2293
D.3.4	Pharmaceutical form	Ointment
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Topical use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BEN2293
D.3.9.2	Current sponsor code	BEN2293
D.3.9.3	Other descriptive name	BEN-00002293
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/W) percent weight/weight
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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)	No
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.IMP: 2
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	BEN2293
D.3.4	Pharmaceutical form	Ointment
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Topical use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	BEN2293
D.3.9.2	Current sponsor code	BEN2293
D.3.9.3	Other descriptive name	BEN-00002293
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/W) percent weight/weight
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.0
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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)	No
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Ointment
D.8.4	Route of administration of the placebo	Topical use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Mild-Moderate Atopic Dermatitis

E.1.1.1

Medical condition in easily understood language

Eczema

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10003639
E.1.2	Term	Atopic dermatitis
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

The primary objective of this study is to assess the safety and tolerability of BEN2293, administered as multiple topical doses to increasing body surface areas, in patients with mild to moderate AD.

E.2.2

Secondary objectives of the trial

• To investigate the plasma PK of BEN2293 and metabolite BEN6403 following multiple topical doses to mild to moderate AD patients.
• To investigate the effect of BEN2293 on pruritus in patients with mild to moderate AD.
• To investigate the effect of BEN2293 on AD in patients with mild to moderate AD.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Males and females with mild to moderate atopic dermatitis (based on vIGA) free from other clinically significant illness or disease that may adversely affect the safety of the patient or the integrity of the study as determined by medical history, physical examination, safety laboratory and other assessments.
3. Patient is aged between18 to 65 years, inclusive.
4. Patient has a body mass index (BMI) of 18.0 to 30.0 kg/m2, inclusive.
5. Body weight of ≥50 kg.
6. History of atopic dermatitis for at least 6 months diagnosed by a dermatologist or GP.
8. A Validated Investigator’s Global Assessment (vIGA) score of 2 (mild) to 3 (moderate) at both Screening and Day -1.
9. Atopic dermatitis affecting between ≥5% to ≤15% Body Surface Area (BSA) of treatable skin (not including face, scalp, hands or soles of feet) at Screening and Day -1 for Cohorts 1 and 2, and between ≥5% to ≤30% BSA of treatable skin (not including face, scalp, hands or soles of feet) at Screening and Day -1 for subsequent cohorts.
10. History of AD associated pruritus with an itch score (NRS) of ≥4. The mean of the pruritus NRS scores (worst itch over the last 24 hours) obtained on Day -3, Day -2 and Day -1 during the emollient only washout phase will be used to assess inclusion.
11. Patients must be willing to stop applying their daily emollients and instead use the study emollient from at least 7 days prior to Day 1 and throughout their participation in the study.
12. Males must use a condom during the trial and for 3 months after their final dose study medication, In addition, their female partner of childbearing potential must be established on an additional method of highly effective contraception prior to dosing until 3 months following final dosing.
13. Female patients of childbearing potential must be established on a highly effective method of contraception prior to dosing until 3 months after last dose in combination with male partner’s use of a condom during the trial and for 3 months after the last dose. Patients must have a negative pregnancy test at Screening and Day 1.
14. Participant has a minimum of one atopic dermatitis area in a site suitable for biopsy.

E.4

Principal exclusion criteria

1. Atopic dermatitis of such severity that the patient could not comply with the demands of the study and/or the patient is not a suitable candidate for a placebo controlled study, as per investigator’s discretion.
2. Any skin tattoo, scar, cuts, bruises, or other skin damage, including excessive UV exposure, at the possible IMP application sites.
3. Patients who have AD lesions affecting >3% untreatable areas (face, scalp, genitals, palms of hands or soles of feet).
4. Patients who have a source of itch solely or significantly from untreatable areas (face, scalp, genitals, palms of hands or soles of feet ).
5. Have concomitant skin disease or infection (e.g. acne, impetigo) or presence of skin comorbidities in the study area to be dosed that may interfere with study assessments.
6. Patients who are excessively hirsute in areas of skin to be dosed with study ointment.
7. Patients who are unwilling to stop hair removal by any means (including shaving, waxing or depilatory creams) to skin areas to be dosed with study ointment for 2 weeks prior to Day -1 and throughout the duration of the study.
12. Positive test for hepatitis B surface antigen (HBsAg), anti-hepatitis C antibody (anti HCV), human immunodeficiency virus I and II (anti-HIV I/II) or SARS-CoV-2 at Screening or Day -1.
17. Supine SBP <90 mmHg >140 mmHg , or DBP <50 mmHg or >90 mmHg after 5 minutes supine and after 3 minutes standing. One repeat is allowed if values are out of range.
22. Patients who have received phototherapy (e.g. UVA, UVB or PUVA therapy), or systemic therapy (e.g., immunosuppressants [such as cyclosporine, azathioprine, methotrexate], cytostatics) known or suspected to have an effect on AD, within 3 months prior to screening. All biologics must not have been used within 6 months prior to screening.
23. Patients who have received systemic corticosteroids (e.g. oral, intravenous, intraarticular, rectal) within 8 weeks prior to screening. Patients on a stable maintenance dose (over the preceding 3 months) of inhaled or intranasal corticosteroids may participate.
24. Patients treated with oral antihistamines within 7 days of screening; intranasal steroid, antihistamine or sodium cromoglycate sprays for the treatment of allergic rhinitis are acceptable.
25. Patients treated with topical calcineurin inhibitors within 1 month of screening.

E.5 End points

E.5.1

Primary end point(s)

- Adverse events
- Local tolerance assessments, vital signs, 12-lead ECG, laboratory safety tests (clinical chemistry, haematology and urinalysis).

E.5.1.1

Timepoint(s) of evaluation of this end point

- Day (-28) to 14 days post last dose
- Maximum evaluated days at Screening, Days 1, 2, 3, 5, 7 and 14. On selected days, these will be measured at pre-dose, 1, 2, 4, 8, 12 and 24 hours post dose

E.5.2

Secondary end point(s)

Secondary PK end points:
• Plasma concentration-time profiles and PK parameters for BEN2293 and BEN6403 including Cmax, tmax, t1/2, area under the plasma concentration vs. time curve (AUC) over a dosing interval (AUCτ).
• Accumulation ratio.
Secondary efficacy endpoints:
• Time to significant itch reduction.
• Time to itch resolution.
• Fraction of patients achieving significant itch reduction.
• Fraction of patients achieving itch resolution.
• Change from baseline in Duration of Itching
• Change from baseline in the Numerical Rating Score (NRS) for Pruritus (Worst Itch over 24 hours).
• Change from baseline in the NRS for Pruritus (Current Itch) .
• Change from baseline in the Eczema Area and Severity Index (EASI) score.
• Number of patients achieving improvement in EASI score.
• Change from baseline in body surface area (BSA) affected by AD in treated area(s).
• Change from baseline in Validated Investigators Global Assessment (vIGA) Score.
• Change from baseline in Patient Oriented Eczema Measure (POEM).
• Change from baseline in Dermatology Life Quality Index (DLQI).
• Change from baseline in EQ-5D.
• Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS).
• Change from baseline in Insomnia Severity Index ([ISI] for Part A, Cohorts 3 and 4 and Part B only).

E.5.2.1

Timepoint(s) of evaluation of this end point

PK assessments:
- Blood samples: on Days 1, 2, 3, 5, 7, 8 and 14 and at follow up visit (14/15 days post last dose). On selected days, these would be measured at predose, 1, 2, 4, 6, 8, 11, 12, 14 and 24 hours postdose.
- Urine samples: on Day 7 at 0-24 hours post dose.

Efficacy assessments:
- Numerical Rating Score (NRS) for Pruritus: predose, Day 1, 2, 3, 5, 7, 8 and 14, and at follow-up after last dose
- Current itch NRS on Day 1 at predose, and 2, 4, and 8 hours postdose
- EASI and vIGA: predose, Days 5, 7, 11, 14 and 21 and at follow-up post last dose
- POEM, PROMIS and DLQI: predose, and at Days 7, 14 and at follow-up post last dose
- EQ-5D: predose and at Day 14
- ISI: predose, Day 14 and at follow-up post last dose

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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)

Yes

E.7.1.1

First administration to humans

Yes

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

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

Yes

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

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

Last Patient Last Visit (LPLV)

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

128

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

130

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-10-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-09-30

P. End of Trial
P.	End of Trial Status	GB - no longer in EU/EEA

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