A study to assess the efficacy and safety of efgartigimod PH20 SC in adults with systemic sclerosis (eSScape)

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], Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

27 Jun 2025 → ongoing

Decision date (initial)

2025-04-15

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

argenx BV

External identifiers

EU CT number

2024-514539-67-00

ClinicalTrials.gov

NCT06655155

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

To evaluate the efficacy of efgartigimod for SC administration coformulated with rHuPH20 (efgartigimod PH20 SC) compared with placebo (placebo PH20 SC) on skin sclerosis in participants with SSc

Secondary objectives 9

1. 1. To evaluate the efficacy of efgartigimod PH20 SC compared with placebo on skin sclerosis in participants with SSc
2. 2. To assess the safety and tolerability of efgartigimod PH20 SC compared with placebo in participants with SSc
3. 3. To evaluate the response to efgartigimod PH20 SC versus placebo based on the Revised Composite Response Index in Systemic Sclerosis (CRISS-25)
4. 4. To evaluate the impact of efgartigimod PH20 SC versus placebo on functioning and disability
5. 5. To evaluate the participant’s and the physician’s assessment of the participant’s overall health
6. 6 To evaluate the impact of efgartigimod PH20 SC versus placebo on lung function
7. 7. To evaluate the pharmacokinetics (PK) of efgartigimod PH20 SC
8. 8. To evaluate pharmacodynamics of efgartigimod PH20 SC
9. 9. To evaluate the immunogenicity of efgartigimod and rHuPH20

Conditions and MedDRA coding

Systemic Sclerosis

Study design 1 period

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Is aged ≥18 years and the local legal age of consent for clinical studies
2. 2. Has diffuse or limited SSc diagnosis and fulfills the 2013 ACR/EULAR classification criteria
3. 3. Has a positive antinuclear antibodies (ANA) test result at the central laboratory with titer of at least 1:160
4. 4. Has a Health Assessment Questionnaire–Disability Index (HAQ-DI) score of at least 0.5 OR a Patient Global Assessment (PGA) score of at least 3
5. 5. Has a modified Rodnan Skin Score (mRSS) score between 15 and 35
6. 6. The participant is anti-RNA polymerase III autoantibody negative at central laboratory and had the first non-Raynaud's phenomenon manifestation less than 5 years before screening or the participant is anti-RNA polymerase III autoantibody positive at central laboratory and had the first non-Raynaud's phenomenon manifestation less than 2 years before screening
7. 7. Has uninvolved or mildly thickened skin area in at least 1 injection site

Exclusion criteria 14

1. 1. Isolated anticentromere antibodies (ACA) seropositivity at the central laboratory
2. 2. Significant Pulmonary Arterial Hypertension
3. 3. Severe digital vasculopathy within the past 3 months
4. 4. Skin thickening due to scleroderma mimics or localized scleroderma
5. 5. Scleroderma renal crisis within the past 6 months of participating to the study
6. 6. Another rheumatic autoimmune disease, except for secondary Sjögren’s syndrome or fibromyalgia
7. 7. Another known autoimmune disease or any medical condition that would interfere with an accurate assessment of SSc or puts the participant at undue risk
8. 8. History of malignancy unless considered cured by adequate treatment, with no evidence of recurrence for 3 years or more before first IMP administration. Adequately treated participants with the following cancers can be included at any time: Basal cell or squamous cell skin cancer; Carcinoma in situ of the cervix; Carcinoma in situ of the breast; Incidental histological finding of prostate cancer
9. 9. Serious or severe active infection that is not sufficiently resolved before baseline OR an active infection that could place the participant at undue risk or confound the study results in the investigator’s opinion
10. 10. Positive serum test for active viral infection with any of the following conditions: Hepatitis B virus (HBV); Hepatitis C virus (HCV); HIV
11. 11. Disease or any other medical condition that, in the investigator’s opinion, would confound the study results or put the participants at undue risk. Recent major surgery or intention to have major surgery during the study
12. 12. History of or current alcohol, drug, or medication abuse
13. 13. Pregnant or lactating state or intention to become pregnant during the study
14. 14. Severe renal impairment

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change from baseline in modified Rodnan Skin Score (mRSS) at week 24

Secondary endpoints 12

1. 1. Change from baseline in mRSS at week 48
2. 2. Incidence and severity of treatment-emergent adverse events (AEs), serious AEs (SAEs), and AEs leading to discontinuation of investigational medicinal product (IMP)
3. 3. Clinically meaningful changes in laboratory parameters, electrocardiograms (ECGs), and vital signs
4. 4. Proportion of participants who improve in ≥2 or ≥3 of the 5 core items of CRISS-25 at weeks 24 and 48 and do not have worsening in >1 component and have no significant SSc-related event(s)
5. 5. Change from baseline in Health Assessment Questionnaire—Disability Index (HAQ-DI) at weeks 24 and 48
6. 6. Change from baseline in Patient Global Assessment (PGA) at weeks 24 and 48
7. 7. Change from baseline in Clinician’s Global Assessment (CGA) at weeks 24 and 48
8. 8. Annualized rate of decline in forced vital capacity (FVC; in mL) in participants with interstitial lung disease (ILD)
9. 9. Efgartigimod serum concentrations over time
10. 10. Percent change from baseline in total IgG levels in serum over time
11. 11. Incidence and prevalence of antidrug antibodies (ADA) against efgartigimod in serum over time
12. 12. Incidence and prevalence of antibodies against recombinant human hyaluronidase PH20 (rHuPH20) in plasma over time

Investigational products

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

Test 1

Placebo 1

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

Chief Scientific Officer

Public contact point

Organisation

Argenx

Contact name

Vice President Clinical Development

Third parties 22

Locations

16 EU/EEA countries · 44 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 210 files

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

Application history

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