Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04833894
Recruitment Status : Recruiting
First Posted : April 6, 2021
Last Update Posted : April 20, 2022
Sponsor:
Information provided by (Responsible Party):
argenx

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)

Condition or disease Intervention/treatment Phase
Generalized Myasthenia Gravis Biological: Efgartigimod IV Phase 2 Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : October 26, 2021
Estimated Primary Completion Date : December 31, 2022
Estimated Study Completion Date : March 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Efgartigimod
Patients receiving efgartigimod intravenous (IV) treatment
Biological: Efgartigimod IV
Intravenous infusion of Efgartigimod




Primary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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


Secondary Outcome Measures :
  1. Incidence and severity of adverse events (AEs), serious adverse events (SAEs) and adverse events of special interest (AESIs) [ Time Frame: up to 28 weeks ]
  2. Efgartigimod serum concentrations from blood samples [ Time Frame: up to 26 weeks ]
  3. Absolute values of levels of total Immunoglobulin G (IgG) from blood samples [ Time Frame: up to 26 weeks ]
  4. Change from baseline of levels of total Immunoglobulin G (IgG) from blood samples [ Time Frame: up to 26 weeks ]
  5. Percentage change from baseline of total Immunoglobulin G (IgG) from blood samples [ Time Frame: up to 26 weeks ]
  6. Absolute values of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples [ Time Frame: up to 26 weeks ]
  7. Change from baseline of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples [ Time Frame: up to 26 weeks ]
  8. Percentage change from baseline of anti-acetylcholine receptor antibodies (AChR-Ab) from blood samples [ Time Frame: up to 26 weeks ]
  9. Incidence of anti-drug antibodies (ADAs) against efgartigimod in serum samples [ Time Frame: up to 28 weeks ]
  10. Prevalence of anti-drug antibodies (ADAs) against efgartigimod in serum samples [ Time Frame: up to 28 weeks ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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 ]
  15. 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.

  16. 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.

  17. Values of Neurological Quality of Life (Neuro-QoL) pediatric fatigue questionnaire [ Time Frame: up to 26 weeks ]
  18. Change from baseline of Neurological Quality of Life (Neuro-QoL) pediatric fatigue questionnaire [ Time Frame: up to 26 weeks ]
  19. Change in protective antibody titers to vaccines received before or during the trial from blood samples [ Time Frame: up to 28 weeks ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   2 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04833894


Contacts
Layout table for location contacts
Contact: Antonio Guglietta, MD 857-350-4834 ClinicalTrials@argenx.com

Locations
Layout table for location information
Belgium
Investigator Site 5 - BE0320021 Recruiting
Antwerpen, Belgium, 2650
Contact: Antonio Guglietta, MD    8573504834    clinicaltrials@argenx.com   
France
Investigator Site 4 - FR0330032 Recruiting
Marseille, France, 13004
Contact: Antonio Guglietta, MD    8573504834    clinicaltrials@argenx.com   
Georgia
Investigator Site 1 - GEO9950017 Recruiting
Tbilisi, Georgia, 0177
Contact: Antonio Guglietta, MD    857-350-4834    clinicaltrials@argenx.com   
Investigator Site 2 - GEO9950018 Recruiting
Tbilisi, Georgia, 0186
Contact: Antonio Guglietta, MD    857-350-4834    clinicaltrials@argenx.com   
Poland
Investigator Site 9 - PL0480035 Not yet recruiting
Gdańsk, Woj. Pomorskie, Poland, 80-952
Contact: Antonio Guglietta    8573504834    clinicaltrials@argenx.com   
Investigator Site 8 - PL0480038 Not yet recruiting
Katowice, Woj. Slaskie, Poland, 40-123
Contact: Antonio Guglietta, MD    8573504834    clinicaltrials@argenx.com   
Investigator Site 6 - PL0480034 Recruiting
Warszawa, Poland, 02-097
Contact: Antonio Guglietta, MD    8573504834    clinicaltrials@argenx.com   
Spain
Investigator Site 7 - ES0340040 Not yet recruiting
Barcelona, Cataluña, Spain, 08950
Contact: Antonio Guglietta, MD    8573504834    clinicaltrials@argenx.com   
Investigator Site 3 - ES0340041 Recruiting
Valencia, Spain, 46026
Contact: Antonio Guglietta, MD    857-350-4834    clinicaltrials@argenx.com   
Sponsors and Collaborators
argenx
Layout table for additonal information
Responsible Party: argenx
ClinicalTrials.gov Identifier: NCT04833894    
Other Study ID Numbers: ARGX-113-2006
First Posted: April 6, 2021    Key Record Dates
Last Update Posted: April 20, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Myasthenia Gravis
Muscle Weakness
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Pathologic Processes
Paraneoplastic Syndromes, Nervous System
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Paraneoplastic Syndromes
Autoimmune Diseases of the Nervous System
Neurodegenerative Diseases
Neuromuscular Junction Diseases
Neuromuscular Diseases
Autoimmune Diseases
Immune System Diseases