Adjusted brodalumab dose compared with standard brodalumab dose in subjects with moderate-to-severe plaque psoriasis and ≥120 kg body weight; ADJUST

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Leo Pharma A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17], Diseases [C] - Immune System Diseases [C20]

Trial duration

15 Jun 2022 → 6 Jan 2026

Decision date (initial)

2024-06-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

LEO Pharma A/S

External identifiers

EU CT number

2023-509668-11-00

EudraCT number

2017-004998-13

ClinicalTrials.gov

NCT04306315

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To compare the effect on psoriasis symptoms of an adjustable brodalumab dosage regimen to standard brodalumab treatment in subjects with moderate-to severe psoriasis and a body weight ≥120 kg

Secondary objectives 4

1. To evaluate the safety of an adjustable brodalumab dosage regimen in subjects with moderate-to-severe psoriasis and a body weight ≥120 kg.
2. To evaluate pharmacokinetics (PK) of brodalumab in subjects with moderateto- severe psoriasis and a body weight ≥120 kg.
3. To explore the effect of brodalumab on systemic inflammation in subjects with moderate-to-severe psoriasis and a body weight ≥120 kg.
4. To explore the effect of brodalumab on skin and subcutaneous adipose tissue inflammation in subjects with moderate-to-severe psoriasis and a body weight ≥120 kg.

Conditions and MedDRA coding

Moderate-to-severe plaque psoriasis and a body weight ≥120 kg.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Signed and dated informed consent has been obtained prior to any protocol-related procedures.
2. Age ≥18 to <75 years at the time of screening.
3. Diagnosed with chronic plaque psoriasis at least 6 months before randomisation as determined by the investigator.
4. Body weight ≥120 kg at the time of screening.
5. Moderate-to-severe plaque psoriasis as defined by: BSA ≥10% and PASI ≥12 at screening and baseline.
6. No evidence of active or latent tuberculosis according to local standard of care for patients requiring initiation of a biologic treatment.

Exclusion criteria 10

1. Diagnosed with erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication-induced psoriasis, or other skin conditions (e.g., eczema) that would interfere with evaluations of the effect of the investigational medicinal product (IMP) on subjects with plaque psoriasis.
2. Clinically important active infections or infestations, chronic, recurrent or latent infections or infestations, or is immunocompromised (e.g., human immunodeficiency virus, hepatitis B, and hepatitis C).
3. Any systemic disease considered by the investigator to be uncontrolled and either immunocompromising the subject and/or placing the subject at undue risk of intercurrent diseases (including, but not limited to, renal failure, heart failure, liver disease, diabetes, and anaemia).
4. Known history of Crohn’s disease.
5. Myocardial infarction or stroke, or unstable angina pectoris within the past 12 months.
6. Any active malignancy.
7. History of malignancy within 5 years, except for treated and considered cured cutaneous squamous or basal cell carcinoma, in situ cervical cancer, or in situ breast ductal carcinoma.
8. History of suicidal behaviour (i.e., ‘actual suicide attempt’, ‘interrupted attempt’, ‘aborted attempt’, or ‘preparatory acts or behaviour’) based on the Columbia-Suicide Severity Rating Scale (C-SSRS) questionnaire at screening or at baseline.
9. Any suicidal ideation of category 4 or 5 (‘active suicidal ideation with some intent to act, without specific plan’ or ‘ active suicidal ideation with specific plan and intent’) based on the C-SSRS questionnaire at screening or at baseline.
10. A Patient Health Questionnaire (PHQ)-8 score of ≥10 corresponding to moderate-to-severe depression at screening or at baseline.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Having at least 90% lower Psoriasis Area and Severity Index (PASI) score relative to baseline (PASI 90 response) at Week 40.

Secondary endpoints 13

1. Having static Physician’s Global Assessment (sPGA) score of 0 or 1 at Week 40.
2. Having PASI 90 response at Week 52.
3. Having sPGA score of 0 or 1 at Week 52.
4. Having sPGA of genitalia (sPGA-G) of 0 or 1 at both Weeks 40 and 52.
5. Having sPGA-G score of 0 or 1 at Week 40.
6. Having sPGA-G score of 0 or 1 at Week 52.
7. Having PASI 100 response at Week 40.
8. Having PASI 100 response at Week 52.
9. Change from baseline at Weeks 40 and 52 in PASI score.
10. Change from baseline at Weeks 40 and 52 in affected body surface area (BSA).
11. Having Dermatology Life Quality Index (DLQI) total score of 0 or 1 at Week 40.
12. Having DLQI total score of 0 or 1 at Week 52.
13. Change from baseline at Weeks 40 and 52 in DLQI total score.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Leo Pharma A/S

Sponsor organisation

Leo Pharma A/S

Address

Industriparken 55

City

Ballerup

Postcode

2750

Country

Denmark

Scientific contact point

Organisation

Leo Pharma A/S

Contact name

LEO Pharma Clinical Trials mailbox

Public contact point

Organisation

Leo Pharma A/S

Contact name

LEO Pharma Clinical Trials mailbox

Third parties 9

Locations

9 EU/EEA countries · 64 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 52 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications