A Study to Evaluate the Efficacy and Safety of Dupilumab in Adult Patients with Bullous Pemphigoid

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Regeneron Pharmaceuticals Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

11 Nov 2020 → 5 Jan 2025

Decision date (initial)

2024-08-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Regeneron Pharmaceuticals Inc.

External identifiers

EU CT number

2024-510745-34-00

EudraCT number

2019-003520-20

ClinicalTrials.gov

NCT04206553

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The primary objective of the study is to demonstrate that dupilumab is superior to placebo in achieving sustained remission off OCS in patients with Bullous Pemphigoid (BP).

Secondary objectives 7

1. To evaluate the OCS-sparing effects of dupilumab in patients with BP.
2. To evaluate the effect of dupilumab on itch in patients with BP.
3. To evaluate the effects of dupilumab on health-related quality of life measures in patients with BP.
4. To evaluate the effect of dupilumab in circulating BP180 and BP230 autoantibody titers.
5. To assess the safety and tolerability of dupilumab administered to patients with BP.
6. To characterize the trough concentrations of functional dupilumab over time following administration of dupilumab in patients with BP.
7. To assess the immunogenicity of dupilumab in patients with BP over time.

Conditions and MedDRA coding

Bullous Pemphigoid

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male or female, age 18 to 90 at the screening visit.
2. Patients must have characteristic clinical features of bullous pemphigoid (BP) (eg, urticarial or eczematous or erythematous plaques, bullae, pruritus) at the screening and baseline visits.
3. Study participants are required to have a confirmed diagnosis of BP based on histopathology, immunopathology, and serology at the baseline visit, as defined in the protocol.
4. Bullous Pemphigoid Disease Area Index (BPDAI) activity score ≥24 at baseline and screening visits.
5. Baseline peak pruritus NRS score for maximum itch intensity ≥4.
6. Karnofsky performance status score ≥50% at the screening visit.
7. Note: Other Protocol Defined Inclusion Criteria Apply

Exclusion criteria 8

1. Forms of pemphigoid other than classic BP (eg, Brunsting-Perry cicatricial pemphigoid, anti-p200 pemphigoid, epidermolysis bullosa acquisita, or BP with concomitant pemphigus vulgaris).
2. Patients who are receiving treatments known to cause or exacerbate BP (eg, angiotensin converting enzyme inhibitors, penicillamine, furosemide, phenacetin, dipeptidyl peptidase 4 inhibitor) who have not been on a stable dose of these medications for at least 4 weeks prior to the screening visit.
3. Have ever received treatment with an IL-4 or IL-13 antagonist such as dupilumab, tralokinumab, or lebrikizumab.
4. Treatment with systemic corticosteroids within 7 days before the baseline visit.
5. Treatment with topical corticosteroids of medium potency or higher, topical calcineurin inhibitor, or topical crisaborole within 7 days before the baseline visit.
6. Treatment with non-steroidal immunosuppressive/immunomodulating drug(s) (eg, mycophenolate mofetil, azathioprine, or methotrexate) within 4 weeks before the baseline visit.
7. Treatment with BP-directed biologics as follows: (a) Any cell-depleting agents including but not limited to rituximab: within 12 months before the baseline visit, or until lymphocyte and CD 19+ lymphocyte count returns to normal, whichever is longer, (b) Other biologics (such as IL-5 inhibitors benralizumab or mepolizumab): within 5 half-lives (if known) or 16 weeks prior to the baseline visit, whichever is longer, and (c) Intravenous immunoglobulin within 16 weeks prior to the baseline visit.
8. Note: Other Protocol Defined Exclusion Criteria Apply

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of patients achieving sustained remission.

Secondary endpoints 25

1. Total cumulative dose of oral corticosteroids (OCS).
2. Percent change in weekly average of daily peak pruritus numerical rating score (NRS).
3. Proportion of patients with improvement (reduction) of weekly average of daily peak pruritus NRS ≥4.
4. Percent change in Bullous Pemphigoid Disease Area Index Activity Score (BPDAI) activity score.
5. Time to first use of rescue medication.
6. Duration of complete remission while not requiring OCS.
7. Proportion of patients who do not achieve control of disease activity, who relapse after achieving control of disease activity, or do not achieve complete remission.
8. Proportion of patients who achieve a reduction in BPDAI activity score of at least 50%, 75%, and 90%.
9. Change in autoimmune bullous disease quality of life (ABQOL).
10. Change in percent body surface area (BSA) of BP involvement.
11. Change in BP180 autoantibody (IgG) titers.
12. Change in BP230 autoantibody (IgG) titers.
13. Proportion of patients with sustained remission.
14. Total cumulative dose of OCS.
15. Duration of complete remission while not requiring OCS.
16. Percent change in weekly average of daily peak pruritus NRS.
17. Percent change in BPDAI activity score.
18. Change in ABQOL.
19. Change in percent BSA of BP involvement.
20. Proportion of patients in complete remission and off OCS.
21. Incidence of treatment-emergent adverse events (TEAEs).
22. Incidence of treatment-emergent serious adverse events (SAEs).
23. Incidence of adverse events of special interest (AESIs).
24. Concentrations of functional dupilumab in serum.
25. Incidence of treatment-emergent anti-drug antibody (ADA) responses and titer.

Investigational products

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

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Regeneron Pharmaceuticals Inc.

Sponsor organisation

Regeneron Pharmaceuticals Inc.

Address

777 Old Saw Mill River Road

City

Tarrytown

Postcode

10591-6717

Country

United States

Scientific contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Public contact point

Organisation

Regeneron Pharmaceuticals Inc.

Contact name

Medical Affairs

Third parties 10

Locations

4 EU/EEA countries · 23 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 27 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