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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT04833894

Studienbeginn:
Oktober 2021

Letztes Update:
11.04.2024

Wirkstoff:
efgartigimod IV

Indikation (Clinical Trials):
Myasthenia Gravis, Muscle Weakness

Geschlecht:
Alle

Altersgruppe:
Alle

Phase:
-

Sponsor:
argenx

Collaborator:
-

Kontakt

Studienlocations
(3 von 24)

Charité - Universitätsmedizin Berlin
13353 Berlin
(Berlin)
GermanyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Corinna Stoltenburg, MD
Phone: 857-350-4834
E-Mail: clinicaltrials@argenx.com» Ansprechpartner anzeigen
Kinderonkologisches Zentrum Universitätsklinikum Essen
Hufelandstraße 55
45147 Essen
DeutschlandNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Adela Della Marina, MD
Phone: 8573504834
E-Mail: clinicaltrials@argenx.com» Ansprechpartner anzeigen
Ann and Robert H Lurie Childrens Hospital of Chicago
60611 Chicago
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Nancy Kuntz, MD
Phone: 857-350-4834
E-Mail: clinicaltrials@argenx.com» Ansprechpartner anzeigen
University of North Carolina at Chapel Hill
27599 Chapel Hill
United StatesNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
James Howard, MD
Phone: 857-350-4834
E-Mail: clinicaltrials@argenx.com» Ansprechpartner anzeigen
LEPL ''Tblisi State Medical University Givi Zhvani
0186 Tbilisi
GeorgiaNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Sophia Bakhtadze, MD
Phone: 857-350-4834
E-Mail: clinicaltrials@argenx.com» Ansprechpartner anzeigen
Azienda Ospedaliero Universitaria Consorziale Policlinico di Bari
70120 Bari
ItalyNoch nicht rekrutierend» Google-Maps
Ansprechpartner:
Emilia Matera, MD
Phone: 857-350-4834
E-Mail: clinicaltrials@argenx.com» Ansprechpartner anzeigen
Uniwersyteckie Centrum Kliniczne WUM, Centralny Szpital Kliniczny
02-097 Warszawa
PolandRekrutierend» Google-Maps
Ansprechpartner:
Anna Kostera-Pruszczyk, MD
Phone: 8573504834
E-Mail: clinicaltrials@argenx.com» Ansprechpartner anzeigen
Hospital Universitari i Politecnic La Fe de Valencia
46026 Valencia
SpainRekrutierend» Google-Maps
Ansprechpartner:
Teresa Sevilla Mantecón, MD
Phone: 857-350-4834
E-Mail: clinicaltrials@argenx.com» Ansprechpartner anzeigen
Oxford University hospitals NHS Foundation Trust-Oxford Children's Hospital
OX3 9DU Oxford
United KingdomRekrutierend» Google-Maps
Ansprechpartner:
Sithara Ramdas, MD
Phone: 857-350-4834
E-Mail: Clinicaltrials@argenx.com» Ansprechpartner anzeigen
Alle anzeigen

Studien-Informationen

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)

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

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:

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)

Geprüfte Regime

  • Efgartigimod IV:
    Intravenous infusion of Efgartigimod

Quelle: ClinicalTrials.gov


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