A study of efgartigimod PH20 SC in children between 2 and less than 18 years of age with generalized myasthenia gravis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Argenx

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

6 Sep 2024 → ongoing

Decision date (initial)

2024-07-26

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

argenx BV

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Others, Pharmacokinetic, Efficacy

To confirm an appropriate dose of efgartigimod PH20 SC in pediatric participants with gMG

Secondary objectives 1

1. To evaluate the safety and tolerability of efgartigimod PH20 SC in pediatric participants with gMG • To evaluate the PK and PD of efgartigimod PH20 SC in pediatric participants with gMG • To evaluate the immunogenicity of efgartigimod PH20 SC in pediatric participants with gMG • To evaluate the activity and impact on the QoL of pediatric participants with gMG who received efgartigimod PH20 SC • To evaluate the effects of efgartigimod PH20 SC on antibody response to vaccines in pediatric participants with gMG

Conditions and MedDRA coding

Generalized Myasthenia Gravis

Study design 3 periods

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-002597-PIP05-21

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. The participant (and/or their legally authorized representative) understands the requirements of the study and is capable of providing written informed consent/assent and complying with protocol requirements. • The participant is aged 2 to <18 years at the time of informed consent/assent. • The participant has been diagnosed with generalised Myasthenia Gravis that is supported by a physical examination and confirmed seropositivity for anti-acetylcholine receptor antibodies • The participant has had an unsatisfactory response to immunosuppressants, corticosteroids, or acetylcholinesterase inhibitors but is on stable concomitant MG therapy. If receiving corticosteroids and/or immunosuppressants, must be on a stable dose for ≥1 month before screening. • The participant agrees to use birth control consistent with local regulations and people of child-bearing potential must have a negative blood pregnancy test at screening and a negative urine pregnancy test before receiving the study drug.

Exclusion criteria 1

1. Is a female adolescent of child-bearing potential who is pregnant and/or lactating or intends to become pregnant during their participation in the study. • Has worsening muscle weakness secondary to a concurrent infection or as a result of a medication. • Has a documented lack of clinical response to plasma exchange (PLEX). • Received a live or live-attenuated vaccine within <4 weeks before screening. • Received a thymectomy within 3 months before screening or is planning to get a thymectomy during their participation in the study. • Has a known autoimmune disease or any medical condition that would interfere with an accurate assessment of clinical symptoms of generalised Myasthenia Gravis or puts the participant at undue risk. • History of malignancy, cancer, unless considered cured by adequate treatment with no evidence of recurrence for ≥3 years. 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 findings of prostate cancer • Clinically significant active infection that is not sufficiently resolved in the investigator’s opinion or positive serum test at screening for active infection with any of the following: Hepatitis B virus (HBV), Hepatitis C virus (HCV), HIV • Has a positive PCR test for SARS-CoV-2 at screening. • Has/had a clinically significant disease, had recent major surgery (within 3 months of screening) or intends to have major surgery during the study, or has/had any other medical condition that, in the investigator’s opinion, would confound the results of the study or put the participant at undue risk. • Has received a different study drug in another clinical study within <12 weeks before screening. • Is currently participating in another interventional clinical study. • Has previously participated in an efgartigimod clinical study and received at least one dose of study drug. • Has a known hypersensitivity to study drug or any of its excipients • Has a history of or current episode of alcohol, drug, or medication abuse as assessed by the investigator. • Use of some medications before screening (more information is found in the protocol) The complete list of exclusion criteria can be found in the protocol.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Efgartigimod serum concentrations as input for compartmental, model-driven analysis to determine age and size dependency of CL and Vd 2. PD parameters: total IgG levels and AChR-Ab as input for PK/PD modeling analysis

Secondary endpoints 3

1. Incidence and severity of adverse events (AEs), including serious AEs and AEs of special interest • Changes in vital signs, electrocardiogram (ECGs), and clinical laboratory tests • Efgartigimod serum concentrations • Total IgG and AChR-Ab levels: absolute values, changes from baseline values, and percent (%) reductions from baseline values"
2. Prevalence and incidence of antidrug antibodies (ADA) against efgartigimod and antibodies against rHuPH20 • Myasthenia Gravis Activities of Daily Living (MG-ADL) total score: absolute value and change from baseline appropriate for pediatric use • Quantitative Myasthenia Gravis (QMG): absolute value and change from baseline "
3. EQ-5D-Y: absolute value and change from baseline • Quality of Life in Neurological Disorders Questionnaire (Neuro-QoL) Pediatric Fatigue Score: change from baseline • Clinical Global Impression of Improvement (CGI-I): change from baseline • Changes in protective antibody titers to vaccines

Investigational products

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

Test 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 12

Locations

8 EU/EEA countries · 11 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 149 files

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

Application history

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