Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of Efgartigimod Administered Intravenously in Children With Generalized Myasthenia Gravis

• Register: EUCTR
• Last refreshed on: 17 August 2021
• Main ID: EUCTR2020-005841-18-Outside-EU/EEA
• Date of registration: 12/08/2021
• Prospective Registration: Yes
• Primary sponsor: argenx BV
• Public title: Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of Efgartigimod Administered Intravenously in Children With Generalized Myasthenia Gravis
• Scientific title: Open-label Uncontrolled Trial to Evaluate Pharmacokinetics, Pharmacodynamics, Safety, and Activity of Efgartigimod in Children From 2 to Less Than 18 Years of Age With Generalized Myasthenia Gravis. - ADAPT JR
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-005841-18
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no; Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Canada, Georgia, United Kingdom, United States

Contacts

• Name: Regulatory
• Affiliation: argenx BV

• Name: Regulatory
• Affiliation: argenx BV

Key inclusion & exclusion criteria

Inclusion criteria:
1. Ability of the participant and/or his/her legally authorized representative to understand the requirements of the trial and provide written informed consent/assent, if applicable (including consent/assent for the use and disclosure of research-related health information), willingness and ability to comply with the trial protocol procedures (including attending the required trial visits).
2. Male or female participants between 2 to less than 18 years of age at the time of providing informed consent/assent. Age groups are enrolled in a staggered fashion respectively: 6 participants in the 12 to less than 18 years of age group followed by 6 participants in the 2 to less than 12 years of age group at the time of providing informed consent/assent.
3. Diagnosed with gMG with confirmed documentation
4. Meeting the clinical criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, and IVa.
5. Eligible participants should have an unsatisfactory response (efficacy and/or safety) to immunosuppressants, steroids or AChE inhibitors and should be on stable concomitant gMG therapy of adequate duration before screening.
6. Positive serologic test for anti-AChR antibodies at screening (for younger participants (<15kg) historical values can be used).
7. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical trials. A subject is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active.
a. Male participants: Male participants must agree to not donate sperm from the time the ICF was signed until the end of the trial.
b. Female participants:
Female adolescents of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before IMP can be administered.
Are the trial subjects under 18? yes
Number of subjects for this age range: 12
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Participants with MGFA class I, IVb, and V.
2. Female adolescents of childbearing potential (FAOCBP): Pregnancy or lactation, or the participant intends to become pregnant during the trial or within 90 days after the last dose of IMP.
3. Has any of the following medical conditions:
a) Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening.
b) Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of clinical symptoms of myasthenia gravis or put the participant at undue risk.
c) 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:
-Adequately treated 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 (TNM Classification of Malignant Tumors stage T1a or T1b)
d) Clinical evidence of other significant serious diseases, or have had a recent major surgery, or who have any other condition that, in the opinion of the investigator, could confound the results of the trial or put the participant at undue risk.
4. Worsening muscle weakness secondary to concurrent infections or medications (aminoglycosides, fluoro-quinolones, beta-blockers, etc).
5. A documented lack of clinical response to plasma exchange (PLEX).
6. Received a live or live-attenuated vaccine fewer than 28 days before screening. Receiving an inactivated, subunit, polysaccharide, or conjugate vaccine any time before screening is not exclusionary.
7. Received a thymectomy <3 months before screening or 1 is planned to be performed during the trial period.
8. The following results from these diagnostic assessments will be considered exclusionary:
a. Positive serum test at screening for an active viral infection with any of the following conditions:
-Hepatitis B virus (HBV) that is indicative of an acute or chronic infection(https://www.cdc.gov/hepatitis/HBV/PDFs/SerologicChartv8.pdf)
-Hepatitis C virus (HCV) based on HCV antibody assay
-Human immunodeficiency virus (HIV) associated with a CD4 count <200 cells/mm3 with an acquired immunodeficiency syndrome (AIDS)-defining condition, such as: Cytomegalovirus retinitis with loss of vision, Pneumocystis jiroveci pneumonia, chronic intestinal cryptosporidiosis, HIV-related encephalopathy, Mycobacterium tuberculosis (pulmonary or
extrapulmonary), or invasive cervical cancer
b. Positive nasopharyngeal swab PCR test for SARS-CoV-2 at screening.
9. Using the following prior or concomitant therapies:
a. Use of an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of the IMP.
b. Use of any monoclonal antibody within the 6 months before the first dose of the IMP.
c. Use of IVIg, immunoglobulins administered SC or intramuscularly, or PLEX within 4 weeks before screening.
10. Total IgG levels below the lower limit of normal (LLN) according to the reference ranges of the central laboratory for participant by sex and age at screening.
11. A known hypersensitivity reaction to efgartigimod or any of its excipients.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Generalized Myasthenia Gravis
MedDRA version: 21.1 Level: PT Classification code 10028417 Term: Myasthenia gravis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Immune System Diseases [C20]

Intervention(s)

Product Name: efgartigimod
Product Code: ARGX-113
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: EFGARTIGIMOD ALFA
CAS Number: 1821402-21-4
Current Sponsor code: ARGX-113
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Secondary Objective: • To evaluate the safety and tolerability of efgartigimod IV
• To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of efgartigimod IV
• To evaluate the immunogenicity of efgartigimod IV
• To evaluate the activity and impact on quality of life of efgartigimod IV
• To evaluate the effect of efgartigimod treatment on antibody response to vaccines

Primary end point(s): - Efgartigimod concentrations as input for compartmental, model-driven analysis to determine (age and size dependency of) clearance (CL) and volume of distribution (Vd)
- PD parameters: total IgG levels and anti-acetylcholine receptors antibodies (AChR-Ab) as input for PK/PD modeling analysis.

Timepoint(s) of evaluation of this end point: 26 weeks

Main Objective: To confirm an age-adjusted optimum dose of efgartigimod IV and provide (model-predicted) evidence for a treatment response.

Secondary Outcome(s)

Secondary end point(s): -Incidence and severity of adverse events (AEs), incidence of serious adverse events (SAEs)
-Efgartigimod serum concentrations
-Levels of total IgG and anti-acetylcholine receptor antibodies (AChRAb):
absolute values, change from baseline and percent (%) change from baseline
-Incidence and prevalence of anti-drug antibodies (ADAs) against efgartigimod
-MG-ADL: absolute value and change from baseline of total MG-ADL score
-Total QMG score: absolute value and change from baseline of total QMG score
-Total score EQ-5D-Y: absolute value and change from baseline
-Neurological Quality of Life (Neuro-QoL) Pediatric Fatigue Score: values and change from baseline
-Change in protective antibody titers to vaccines received before or
received during the trial

Timepoint(s) of evaluation of this end point: 2nd endpoint 1,4,8 = 28 weeks
2nd endpoint 2,3,5,6,7 = 26 weeks

Secondary ID(s)

2020-005841-18-NL

NCT04833894

ARGX-113-2006

Source(s) of Monetary Support

argenx BV