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

Generalized Myasthenia Gravis Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04833894
• Other study ID #: ARGX-113-2006
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: October 26, 2021
• Est. completion date: August 2024

Study information

• Verified date: April 2024
• Source: argenx
• Contact: Sabine Coppieters, MD
• Phone: 857-350-4834
• Email: ClinicalTrials[@]argenx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this trial is to investigate the PK, PD, safety, and activity of efgartigimod IV in children and adolescents aged from 2 to less than 18 years of age with gMG.

Trial details include:

• The maximum trial duration for each individual participant will be approximately 28 weeks

• The treatment duration will be 8 weeks for the dose-confirmatory part (Part A) and 18 weeks for the treatment response-confirmatory part (Part B)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: August 2024
• Est. primary completion date: August 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 18 Years

Eligibility

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 Generalized Myasthenia Gravis (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 acetylcholinesterase (AChE) inhibitors and should be on stable concomitant gMG therapy of adequate duration before screening.

6. Positive serologic test for acetylcholine receptor (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.

1. Male participants: Male participants must agree to not donate sperm from of providing informed consent/assent until they have completed the trial.

2. 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 investigational medicinal product (IMP) can be administered.

Exclusion Criteria:

1. Participants with MGFA class I, IVb, and V.

2. Female adolescents of childbearing potential: 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:

1. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening.

2. 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.

3. History of malignancy unless deemed cured by adequate treatment with no evidence of recurrence for =3 years before the first administration of 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

4. 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; Hepatitis C virus (HCV) based on HCV antibody assay; Positive HIV serology at screening; Positive nasopharyngeal swab polymerase chain reaction (PCR) test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening.

9. Using the following prior or concomitant therapies: Use of an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of IMP, Use of any monoclonal antibody within the 6 months before the first dose of IMP, Use of intravenous immunoglobulin (IVIg), administered subcutaneously or intramuscularly, or PLEX within 4 weeks before screening.

10. Total immunoglobulin (IgG) levels <6 g/L 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.

12. Current participation in another interventional clinical trial or previous participation in an efgartigimod trial with at least 1 dose of IMP received.

13. History (within 12 months of screening) of current alcohol, drug, or medication abuse as assessed by the investigator.

Related Conditions & MeSH terms

• Generalized Myasthenia Gravis
• Muscle Weakness
• Myasthenia Gravis

Intervention

Biological:
• Efgartigimod IV
Intravenous infusion of Efgartigimod

Locations

Country	Name	City	State
Austria	Medizinische Universitat Wien	Wien
Belgium	UZ Antwerpen	Antwerpen
Canada	British Columbia Children's Hospital	Vancouver
France	Hopitaux de La Timone	Marseille
France	Groupe Hospitalier Necker Enfants Malades	Paris
Georgia	JSC Evex Hospitals	Tbilisi
Georgia	LEPL ''Tblisi State Medical University Givi Zhvani	Tbilisi
Germany	Charité - Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Essen	Essen
Italy	Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari	Bari
Italy	Azienda Ospedaliero Universitaria A. Meyer	Florence
Italy	Istituto G Gaslini Ospedale Pediatrico IRCCS	Genova
Netherlands	Leiden University Medical Center	Leiden
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Woj. Pomorskie
Poland	Wielospecjalistyczna Poradnia Lekarska Synapsis	Katowice	Woj. Slaskie
Poland	Uniwersyteckie Centrum Kliniczne WUM, Centralny Szpital Kliniczny	Warszawa
Spain	Hospital Sant Joan de Deu	Barcelona	Cataluña
Spain	Hospital Universitari i Politecnic La Fe de Valencia	Valencia
United Kingdom	Great Ormond Street Hospital for Children	London
United Kingdom	Royal Manchester Children's Hospital	Manchester
United Kingdom	Oxford University hospitals NHS Foundation Trust-Oxford Children's Hospital	Oxford
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Ann and Robert H Lurie Childrens Hospital of Chicago	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
argenx

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  France,  Georgia,  Germany,  Italy,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efgartigimod concentrations as input for compartmental, model-driven analysis to determine (age and size dependency of) Clearance (CL)	Blood samples will be collected from each participant for measurement of serum concentrations of efgartigimod	up to 26 weeks
Primary	Efgartigimod concentrations as input for compartmental, model-driven analysis to determine (age and size dependency of) Volume of Distribution (Vd)	Blood samples will be collected from each participant for measurement of serum concentrations of efgartigimod	up to 26 weeks
Primary	Total Immunoglobulin G (IgG) levels as input for pharmacokinetics (PK) and pharmacodynamics (PD) modeling analysis	Total Immunoglobulin G levels will be measured from blood samples	up to 26 weeks
Primary	Anti-acetylcholine receptors antibodies (AChR-Ab) as input for pharmacokinetics (PK) and pharmacodynamics (PD) modeling analysis	Total Immunoglobulin G (IgG) levels will be measured from blood samples	up to 26 weeks
Secondary	Incidence and severity of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs)		up to 28 weeks
Secondary	Efgartigimod serum concentrations from blood samples		up to 26 weeks
Secondary	Absolute values of levels of total Immunoglobulin G (IgG) from blood samples		up to 26 weeks
Secondary	Change from baseline of levels of total Immunoglobulin G (IgG) from blood samples		up to 26 weeks
Secondary	Percentage change from baseline of total Immunoglobulin G (IgG) from blood samples		up to 26 weeks
Secondary	Absolute values of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples		up to 26 weeks
Secondary	Change from baseline of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples		up to 26 weeks
Secondary	Percentage change from baseline of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples		up to 26 weeks
Secondary	Incidence of anti-drug antibodies (ADAs) against efgartigimod in serum samples		up to 28 weeks
Secondary	Prevalence of anti-drug antibodies (ADAs) against efgartigimod in serum samples		up to 28 weeks
Secondary	Absolute values of total Myasthenia Gravis Activity of Daily Living (MG-ADL) score. Total score can range from 0 to 24, with higher total scores indicating more impairment.		up to 26 weeks
Secondary	Change from baseline of total Myasthenia Gravis Activity of Daily Living (MG-ADL) score. Total score can range from 0 to 24, with higher total scores indicating more impairment.		up to 26 weeks
Secondary	Absolute values of total Quantitative Myasthenia Gravis Score (QMG score). The total possible score is 39, where higher total scores indicate more severe impairments.		up to 26 weeks
Secondary	Change from baseline of total Myasthenia Gravis Score (QMG score). The total possible score is 39, where higher total scores indicate more severe impairments.		up to 26 weeks
Secondary	Absolute values of total score EuroQoL 5 Dimensions Youth (EQ-5D-Y)	Description of the participant's health state is done by digits for 5 dimensions combined in a 5-digit number. A unique health state is defined by combining 1 level from each of the 5 dimensions. Each state is referred to in terms of a 5-digit code, whereas code 11111 would indicate no problems in any of the 5 dimensions and 33333 would indicate worst problems in any of the 5 dimensions.	up to 26 weeks
Secondary	Change from baseline of total score EuroQoL 5 Dimensions Youth (EQ-5D-Y)	Description of the participant's health state is done by digits for 5 dimensions combined in a 5-digit number. A unique health state is defined by combining 1 level from each of the 5 dimensions. Each state is referred to in terms of a 5-digit code, whereas code 11111 would indicate no problems and 33333 would indicate worst problems in any of the 5 dimensions.	up to 26 weeks
Secondary	Values of Neurological Quality of Life (Neuro-QoL) pediatric fatigue questionnaire		up to 26 weeks
Secondary	Change from baseline of Neurological Quality of Life (Neuro-QoL) pediatric fatigue questionnaire		up to 26 weeks
Secondary	Change in protective antibody titers to vaccines received before or during the trial from blood samples		up to 28 weeks