A phase 2/3 study of efgartigimod PH20 SC in adult participants with bullous pemphigoid

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Argenx

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

10 May 2022 → 14 Sep 2024

Decision date (initial)

2024-02-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

argenx BV

External identifiers

EU CT number

2023-508645-40-00

EudraCT number

2021-003087-27

ClinicalTrials.gov

NCT05267600

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Others, Pharmacodynamic

To evaluate the efficacy of efgartigimod PH20 SC on achieving sustained remission in the treatment of participants with bullous pemphigoid (BP)

Secondary objectives 11

1. To evaluate the corticosteroid-sparing effects of efgartigimod PH20 SC in participants with BP
2. To characterize the overall efficacy of efgartigimod PH20 SC in the treatment of participants with BP
3. To evaluate the efficacy of efgartigimod PH20 SC in preventing relapse of BP
4. To evaluate the effect of efgartigimod PH20 SC on pruritus in participants with BP
5. To assess the safety and tolerability of efgartigimod PH20 SC administered to participants with BP
6. To assess glucocorticoid-associated morbidity and evaluate the impact of efgartigimod PH20 SC on reducing of glucocorticoid toxicity
7. To evaluate the effects of efgartigimod PH20 SC on the quality of life (QoL) of participants with BP
8. To evaluate the pharmacokinetics of efgartigimod PH20 SC in participants with BP
9. To evaluate the pharmacodynamics of efgartigimod PH20 SC in participants with BP
10. To evaluate the immunogenicity of efgartigimod PH20 SC in participants with BP
11. To evaluate the competency of participants or caregivers to (self-) administer efgartigimod PH20 SC

Conditions and MedDRA coding

Bullous Pemphigoid (BP)

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. The participant is willing and able to do the following: a. understand the requirements of the study b. provide written informed consent c. comply with the study protocol procedures.
2. The participant is male or female and has reached the local legal age of consent at the time of signing the informed consent form (ICF)
3. Participants have clinical signs of BP.
4. The participant agrees to use contraceptive measures consistent with local regulations. WOCBP must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before receiving IMP.

Exclusion criteria 15

1. Other forms of pemphigoid or other autoimmune bullous diseaes (AIBDs)
2. Received unstable dose of treatments known to cause or exacerbate BP for at least 4 weeks prior the baseline visit
3. Use of BP treatments other than oral corticosteroids (OCS) , topical corticosteroids (TCS), conventional immunosuppressants or dapsone
4. Known contraindication to OCS therapy
5. Active, chronic, or latent infection at screening
6. Positive COVID-19 test result at screening (testing performed if required per local regulations)
7. History of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥3 years before the first administration of the IMP. Participants with the following cancers can be included at any time, provided they are adequately treated before their participation in the study: a. Basal cell or squamous cell skin cancer b. Carcinoma in situ of the cervix c. Carcinoma in situ of the breast d. Incidental histological finding of prostate cancer
8. Clinical evidence of other significant serious diseases, have had a recent surgery, or who have any other condition that, in the opinion of the investigator, could confound the results of the study or put the patient at undue risk or prevent participants from complying with protocol requirements
9. Use of an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of IMP
10. Previously participated in a clinical study with efgartigimod or currently participating in another interventional clinical study
11. Known hypersensitivity to any of the components of the administered treatments
12. Positive serum test at screening for an active infection with any of the following conditions: a. HBV b. HCV c. HIV
13. Current or history (ie, within 12 months of screening) of alcohol, drug, or medication abuse as assessed by the investigator
14. Pregnant or lactating females and those who intend to become pregnant during the study
15. Live or live-attenuated vaccine received <4 weeks before baseline visit

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Proportion of participants who are in complete remission (CR) while receiving efgartigimod PH20 SC or placebo and have been off oral corticosteroid (OCS) therapy for ≥8 weeks at week 36

Secondary endpoints 26

1. Cumulative dose of OCS from baseline to week 36
2. Proportion of participants who achieve an Investigator Global Assessment of Bullous Pemphigoid (IGA-BP) score of 0 while receiving efgartigimod PH20 SC or placebo and have been off OCS therapy for ≥8 weeks at week 36
3. Proportion of participants who achieve an Investigator Global Assessment of Bullous Pemphigoid (IGA-BP) score of 0 or 1 while receiving efgartigimod PH20 SC or placebo and have been off OCS therapy for ≥8 weeks at week 36
4. Proportion of participants who achieve an IGA-BP score of 0 or 1 while receiving efgartigimod PH20 SC or placebo at any time through week 36
5. Proportion of participants who receive rescue therapy before week 36
6. Proportion of participants who achieve control of disease activity (CDA) while receiving efgartigimod PH20 SC or placebo and remain free of relapse through week 36
7. Proportion of participants who are in CR while receiving efgartigimod PH20 SC or placebo and have been receiving minimal OCS therapy for ≥8 weeks at week 36. (Minimal OCS therapy is defined as ≤0.1 mg/kg/day of prednisone [or an equivalent dose of another OCS].)
8. Changes from baseline in the BPDAI activity score
9. Changes from baseline in the 24-hour average itch score from the Itch Numerical Rating Scale (NRS)
10. Changes from baseline in the 24-hour worst itch score from the Itch Numerical Rating Scale (NRS)
11. Time to achieve the following: - CDA - CR - CR while on minimal OCS therapy for ≥8 weeks - CR/PR while off OCS therapy for ≥8 weeks - CR while off OCS therapy for ≥8 weeks - Relapse
12. Cumulative OCS dose for the participant at the time points when they exhibit the following: - CDA - CR - CR while on minimal OCS therapy for ≥8 weeks - CR/PR while off OCS therapy for ≥8 weeks - CR while off OCS therapy for ≥8 weeks - Relapse
13. Incidence and severity of TEAEs, AESIs, and SAEs
14. The Aggregate Improvement Score (AIS) from the GTI
15. The Cumulative Worsening Score (CWS) from the GTI
16. The GTI Specific List (GTI-SL)
17. EQ-5D-5L scores over time
18. DLQI scores over time
19. ABQoL scores over time
20. EFG serum concentrations
21. Percentage change of total IgG serum levels from baseline over time
22. Percentage change of anti-BP180 and anti-BP230 antibodies from baseline over time
23. Incidence and prevalence of antidrug antibodies (ADA) against efgartigimod (in serum) and antibodies against rHuPH20 (in plasma)
24. Number and percentage of participants (or their caregivers) who complete the (self-)administration training at study sites
25. Number and percentage of participants (or their caregivers) who are determined by site staff to be sufficiently competent in (self-)administering efgartigimod PH20 SC
26. Number and percentage of participants (or their caregivers) who successfully (self-)administer efgartigimod PH20 SC under site staff supervision

Investigational products

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

Test 1

Placebo 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Argenx

Sponsor organisation

Argenx

Address

Industriepark-Zwijnaarde 7

City

Gent

Postcode

9052

Country

Belgium

Scientific contact point

Organisation

Argenx

Contact name

Peter Ulrichts (Chief Scientific Officer)

Public contact point

Organisation

Argenx

Contact name

Peter Ulrichts (Chief Scientific Officer)

Third parties 21

Locations

14 EU/EEA countries · 48 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 2 files

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

Application history

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