The WILLOW study with enpatoran in SLE and CLE (SCLE and/or DLE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Merck Healthcare KGaA

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

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

Trial duration

9 May 2022 → 28 Jan 2025

Decision date (initial)

2024-06-19

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Merck Healthcare KGaA

External identifiers

EU CT number

2024-510872-18-00

EudraCT number

2021-004648-27

ClinicalTrials.gov

NCT05162586

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Therapy, Efficacy, Pharmacodynamic, Pharmacogenetic, Others

To evaluate the dose-response relationship of enpatoran in reducing disease activity based on CLASI-A

Secondary objectives 1

1. To evaluate the dose-response relationship of enpatoran in reducing disease activity based on BICLA response rate

Conditions and MedDRA coding

Systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE)

Study design 1 period

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Active CLE (SCLE and/or DLE) with a CLE disease area and activity index (CLASI-A) >= 8
2. Active SLE with presence of: CLASI-A >= 8 and BILAG 2004 1B, C, D (that is [i.e.], No BILAG 2004 A and No BILAG 2004 >= 2B) or BILAG 2004 >= 1A or 2B and 1 or 2 of the following: Hybrid Safety of Estrogens in Systemic Lupus Erythematosus National Assessment (SELENA)-SLEDAI >= 6 at Screening Visit and confirmed clinical hybrid SELENA-SLEDAI >= 4 (excluding laboratory parameters) at Day 1 Visit and/or CLASI-A >= 8
3. Receiving a stable dose of at least one of the following standards of care therapies for lupus: Immunomodulator/immunosuppressant, oral corticosteroids, and/or topical corticosteroids
4. Other protocol defined inclusion criteria could apply

Exclusion criteria 8

1. Autoimmune or rheumatic disease other than SLE or CLE
2. Dermatological diseases other than cutaneous manifestations of SLE or CLE
3. Uncontrolled medical conditions including significant cardiovascular events, active lupus nephritis, and active neurological disorder
4. Ongoing or active clinically significant viral, bacterial, or fungal infection
5. History of uncontrolled seizures or other neurological disorder
6. History of or positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B virus
7. History of malignancy
8. Other protocol defined exclusion criteria could apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Cohort A: Percent Change from Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-A) at Week 16
2. Cohort B: British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response at Week 24

Secondary endpoints 17

1. Cohort A and Cohort B: Safety Profile as Assessed by Incidence of Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), AEs of Special Interest, Clinically Significant Abnormalities in Laboratory Parameters and QT Interval Corrected
2. Cohort A and Cohort B: Change from Baseline in Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) at Week 16 and Week 24
3. Cohort A and Cohort B: Change from Baseline in Physician's Global Assessment of Cutaneous Lupus Disease Activity at Week 16 and 24
4. Cohort B: Participants with British Isles Lupus Assessment Group (BILAG)-Based Composite Lupus Assessment (BICLA) Response and with Clinically Meaningful Corticosteroids (CS) Reduction
5. Cohort A: Clinically Meaningful Corticosteroids (CS) Reduction
6. Cohort A: Ocurrence of Cutaneous Lupus Activity Investigator's Global Assessment (CLA-IGA) Score 0 or 1 at Week 16 and Week 24
7. Cohort B: Systemic lupus Erythematosus Responder Index-4 (SRI-4) Response at Week 24
8. Cohort B: Lupus Low Disease Activity State (LLDAS) Attainment at Week 24
9. Cohort B: Remission Attainment at Week 24
10. Cohort B: Change From Baseline in Tender Joint Count and Swollen Joint Count at Week 24
11. Cohort B: Change from Baseline in Physician's Global Assessment at Week 24
12. Cohort B: Time to First Moderate/Severe British Isles Lupus Assessment Group (BILAG) Flare
13. Cohort B: Time to First Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI) Severe Flare
14. Cohort A and B: Change from Baseline in Skindex 29+3 Symptom Domain Score at Week 24
15. Cohort A and B: Change from Baseline in the Skindex 29+3 Functioning and Emotion Domain Scores at Week 24
16. Change from Baseline in the Skindex 29+3 Lupus-Specific Domain Score at Week 24
17. Cohort A and B: Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scores at Week 24

Investigational products

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

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Merck Healthcare KGaA

Sponsor organisation

Merck Healthcare KGaA

Address

Frankfurter Strasse 250

City

Darmstadt

Postcode

64293

Country

Germany

Scientific contact point

Organisation

Merck Healthcare KGaA

Contact name

Global Regulatory Affairs

Public contact point

Organisation

Merck Healthcare KGaA

Contact name

Global Regulatory Affairs

Third parties 6

Locations

5 EU/EEA countries · 31 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 121 files

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

Application history

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