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

• ClinicalTrials.gov Identifier: NCT04833894
• Recruitment Status: Recruiting
• First Posted: April 6, 2021
• Last Update Posted: May 3, 2023
• Sponsor: argenx
• Information provided by (Responsible Party): argenx

Tracking Information

• First Submitted Date: March 16, 2021
• First Posted Date: April 6, 2021
• Last Update Posted Date: May 3, 2023
• Actual Study Start Date: October 26, 2021
• Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 2, 2021)

• Efgartigimod concentrations as input for compartmental, model-driven analysis to determine (age and size dependency of) Clearance (CL) [ Time Frame: up to 26 weeks ]
  Blood samples will be collected from each participant for measurement of serum concentrations of efgartigimod
• Efgartigimod concentrations as input for compartmental, model-driven analysis to determine (age and size dependency of) Volume of Distribution (Vd) [ Time Frame: up to 26 weeks ]
  Blood samples will be collected from each participant for measurement of serum concentrations of efgartigimod
• Total Immunoglobulin G (IgG) levels as input for pharmacokinetics (PK) and pharmacodynamics (PD) modeling analysis [ Time Frame: up to 26 weeks ]
  Total Immunoglobulin G levels will be measured from blood samples
• Anti-acetylcholine receptors antibodies (AChR-Ab) as input for pharmacokinetics (PK) and pharmacodynamics (PD) modeling analysis [ Time Frame: up to 26 weeks ]
  Total Immunoglobulin G (IgG) levels will be measured from blood samples

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: June 4, 2021)

• Incidence and severity of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) [ Time Frame: up to 28 weeks ]
• Efgartigimod serum concentrations from blood samples [ Time Frame: up to 26 weeks ]
• Absolute values of levels of total Immunoglobulin G (IgG) from blood samples [ Time Frame: up to 26 weeks ]
• Change from baseline of levels of total Immunoglobulin G (IgG) from blood samples [ Time Frame: up to 26 weeks ]
• Percentage change from baseline of total Immunoglobulin G (IgG) from blood samples [ Time Frame: up to 26 weeks ]
• Absolute values of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples [ Time Frame: up to 26 weeks ]
• Change from baseline of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples [ Time Frame: up to 26 weeks ]
• Percentage change from baseline of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples [ Time Frame: up to 26 weeks ]
• Incidence of anti-drug antibodies (ADAs) against efgartigimod in serum samples [ Time Frame: up to 28 weeks ]
• Prevalence of anti-drug antibodies (ADAs) against efgartigimod in serum samples [ Time Frame: up to 28 weeks ]
• 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. [ Time Frame: up to 26 weeks ]
• 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. [ Time Frame: up to 26 weeks ]
• Absolute values of total Quantitative Myasthenia Gravis Score (QMG score). The total possible score is 39, where higher total scores indicate more severe impairments. [ Time Frame: up to 26 weeks ]
• Change from baseline of total Myasthenia Gravis Score (QMG score). The total possible score is 39, where higher total scores indicate more severe impairments. [ Time Frame: up to 26 weeks ]
• Absolute values of total score EuroQoL 5 Dimensions Youth (EQ-5D-Y) [ Time Frame: up to 26 weeks ]
  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.
• Change from baseline of total score EuroQoL 5 Dimensions Youth (EQ-5D-Y) [ Time Frame: up to 26 weeks ]
  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.
• Values of Neurological Quality of Life (Neuro-QoL) pediatric fatigue questionnaire [ Time Frame: up to 26 weeks ]
• Change from baseline of Neurological Quality of Life (Neuro-QoL) pediatric fatigue questionnaire [ Time Frame: up to 26 weeks ]
• Change in protective antibody titers to vaccines received before or during the trial from blood samples [ Time Frame: up to 28 weeks ]

Original Secondary Outcome Measures (submitted: April 2, 2021)

• Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: up to 28 weeks ]
• Efgartigimod serum concentrations from blood samples [ Time Frame: up to 26 weeks ]
• Absolute values of levels of total Immunoglobulin G (IgG) from blood samples [ Time Frame: up to 26 weeks ]
• Change from baseline of levels of total Immunoglobulin G (IgG) from blood samples [ Time Frame: up to 26 weeks ]
• Percentage change from baseline of total Immunoglobulin G (IgG) from blood samples [ Time Frame: up to 26 weeks ]
• Absolute values of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples [ Time Frame: up to 26 weeks ]
• Change from baseline of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples [ Time Frame: up to 26 weeks ]
• Percentage change from baseline of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples [ Time Frame: up to 26 weeks ]
• Incidence of anti-drug antibodies (ADAs) against efgartigimod in serum samples [ Time Frame: up to 28 weeks ]
• Prevalence of anti-drug antibodies (ADAs) against efgartigimod in serum samples [ Time Frame: up to 28 weeks ]
• 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. [ Time Frame: up to 26 weeks ]
• 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. [ Time Frame: up to 26 weeks ]
• Value of total Quantitative Myasthenia Gravis Score (QMG score). The total possible score is 39, where higher total scores indicate more severe impairments. [ Time Frame: up to 26 weeks ]
• Change from baseline of total Myasthenia Gravis Score (QMG score). The total possible score is 39, where higher total scores indicate more severe impairments. [ Time Frame: up to 26 weeks ]
• Values of total score EuroQoL 5 Dimensions Youth (EQ-5D-Y) [ Time Frame: up to 26 weeks ]
  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.
• Change from baseline of total score EuroQoL 5 Dimensions Youth (EQ-5D-Y) [ Time Frame: up to 26 weeks ]
  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.
• Values of Neurological Quality of Life (Neuro-QoL) pediatric fatigue questionnaire [ Time Frame: up to 26 weeks ]
• Change from baseline of Neurological Quality of Life (Neuro-QoL) pediatric fatigue questionnaire [ Time Frame: up to 26 weeks ]
• Change in protective antibody titers to vaccines received before or during the trial from blood samples [ Time Frame: up to 28 weeks ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief 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)

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2; Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Generalized Myasthenia Gravis

Intervention

Biological: Efgartigimod IV

Intravenous infusion of Efgartigimod

Study Arms

Experimental: Efgartigimod

Patients receiving efgartigimod intravenous (IV) treatment

Intervention: Biological: Efgartigimod IV

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: April 2, 2021): 12
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: March 2024
• Estimated Primary Completion Date: March 2024 (Final data collection date for primary outcome measure)

Eligibility 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 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 Generalized Myasthenia Gravis (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 the time the informed consent form was signed until the end of 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 Myasthenia Gravis Foundation of America (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 investigational medicinal product (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 the investigational medicinal product (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)
   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:

   1. 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
      • 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
   2. 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:

   1. Use of an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of the investigational medicinal product (IMP).
   2. Use of any monoclonal antibody within the 6 months before the first dose of the investigational medicinal product (IMP).
   3. Use of intravenous immunoglobulin (IVIg), administered subcutaneously or intramuscularly, or Plasma exchange (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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Sabine Coppieters, MD; 857-350-4834; ClinicalTrials@argenx.com

• Listed Location Countries: Austria, Belgium, France, Georgia, Germany, Italy, Netherlands, Poland, Spain, United States

Administrative Information

• NCT Number: NCT04833894
• Other Study ID Numbers: ARGX-113-2006
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: argenx
• Original Responsible Party: Same as current
• Current Study Sponsor: argenx
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: argenx
• Verification Date: May 2023