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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Argenx

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

27 Oct 2021 → ongoing

Decision date (initial)

2024-06-25

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Argenx BV

External identifiers

EU CT number

2024-513854-31-00

EudraCT number

2020-005841-18

ClinicalTrials.gov

NCT04833894

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Therapy, Pharmacokinetic, Pharmacodynamic, Safety, Dose response, Efficacy

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

Secondary objectives 5

1. To evaluate the safety and tolerability of efgartigimod IV
2. To evaluate the PK and PD of efgartigimod IV
3. To evaluate the immunogenicity of efgartigimod IV
4. To evaluate the activity and impact on quality of life of efgartigimod IV
5. To evaluate the effect of efgartigimod treatment on antibody response to vaccines

Conditions and MedDRA coding

Generalized Myasthenia Gravis

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-002597-PIP01-19

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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, willingness and ability to comply with the trial protocol procedures.
2. Male or female participants between 2 to < 18 years of age 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).

Exclusion criteria 7

1. Participants with MGFA class I, IVb, and V.
2. Worsening muscle weakness secondary to concurrent infections or medications (aminoglycosides, fluoro-quinolones, beta-blockers, etc).
3. A documented lack of clinical response to plasma exchange (PLEX).
4. 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.)
5. Received a thymectomy <3 months before screening or 1 is planned to be performed during the trial period.
6. A known hypersensitivity reaction to efgartigimod or any of its excipients.
7. Current participation in another interventional clinical trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

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

Secondary endpoints 9

1. Incidence and severity of AEs, incidence of serious AEs (SAEs), incidence of AEs of special interest (AESIs), and changes in laboratory test results, physical examination results, vital sign measurements, and electrocardiogram (ECG) (part B only for ECGs)
2. Efgartigimod serum concentrations
3. Levels of total IgG and AChR-Ab: absolute values, change from baseline and percent (%) change from baseline
4. Incidence and prevalence of antidrug antibodies (ADAs) against efgartigimod
5. MG-ADL total score: absolute value and change from baseline total MG-ADL score
6. Total QMG score: absolute value and change from baseline
7. Total score EQ-5D-Y: absolute value and change from baseline
8. Quality of Life in Neurological Disorders (Neuro-QoL) Pediatric Fatigue Score: values and change from baseline
9. Change in protective antibody titers to vaccines received before or received during the trial

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Argenx

Sponsor organisation

Argenx

Address

Industriepark-Zwijnaarde 7

City

Gent

Postcode

9052

Country

Belgium

Scientific contact point

Organisation

Argenx

Contact name

Chief Scientific Officer

Public contact point

Organisation

Argenx

Contact name

Vice President Clinical Development

Third parties 12

Locations

7 EU/EEA countries · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 88 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

11 submissions — initial application plus substantial / non-substantial modifications