Clinical Trials Register

Summary
EudraCT Number:	2020-004085-19
Sponsor's Protocol Code Number:	ARGX-113-2001
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-12-29
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2020-004085-19

A.3

Full title of the trial

A Phase 3, Randomized, Open-Label, Parallel-Group Study to Compare the Pharmacodynamics, Pharmacokinetics, Efficacy, Safety, Tolerability, and Immunogenicity of Multiple Subcutaneous Injections of Efgartigimod PH20 SC with Multiple Intravenous Infusions of Efgartigimod in Patients with Generalized Myasthenia Gravis (ADAPT)

III. fázisú, randomizált, nyílt, párhuzamos csoportos vizsgálat a többszörös szubkután efgartigimod PH20 SC injekciók farmakodinámiájának, farmakokinetikájának, hatásosságának, biztonságosságának, tolerálhatóságának és immunogenitásának a többszörös intravénás efgartigimod infúziókkal szembeni összehasonlítására generalizált myasthenia gravisban szenvedő betegek körében

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Evaluating the Pharmacodynamic Noninferiority of Efgartigimod PH20 Administered Subcutaneously as Compared to Efgartigimod Administered Intravenously in Patients With Generalized Myasthenia Gravis

A szubkután alkalmazott efgartigimod PH20 SC farmakodinámiás noninferioritásának értékelése az intravénásan alkalmazott efgartigimoddal szembeni összehasonlítása generalizált myasthenia gravisban szenvedő betegek körében

A.3.2

Name or abbreviated title of the trial where available

ADAPT SC

A.4.1

Sponsor's protocol code number

ARGX-113-2001

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	argenx BV
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	argenx BV
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	argenx BV
B.5.2	Functional name of contact point
B.5.3	Address:
B.5.3.1	Street Address	Industriepark Zwijnaarde 7
B.5.3.2	Town/ city	Zwijnaarde (Ghent)
B.5.3.3	Post code	9052
B.5.3.4	Country	Belgium
B.5.4	Telephone number	329310 3400
B.5.6	E-mail	regulatory@argenx.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EMA/OD/245/17
D.3 Description of the IMP
D.3.1	Product name	Efgartigimod PH20 SC
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EFGARTIGIMOD ALFA
D.3.9.1	CAS number	1821402-21-4
D.3.9.2	Current sponsor code	ARGX-113
D.3.9.4	EV Substance Code	SUB198780
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	180
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Efgartigimod IV
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	EFGARTIGIMOD ALFA
D.3.9.1	CAS number	1821402-21-4
D.3.9.2	Current sponsor code	ARGX-113
D.3.9.4	EV Substance Code	SUB198780
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	20
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Generalized Myasthenia Gravis

E.1.1.1

Medical condition in easily understood language

Myasthenia Gravis in patients who have generalized Muscle Weakness

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10028417
E.1.2	Term	Myasthenia gravis
E.1.2	System Organ Class	10029205 - Nervous system disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate that the PD effect of injections of 1000 mg efgartigimod PH20 SC, administered once per week (q7d) for 4 administrations, is noninferior to that of IV infusions of efgartigimod at a dose of 10 mg/kg administered q7d for 4 administrations.

E.2.2

Secondary objectives of the trial

• To compare the PD effect of efgartigimod PH20 SC and efgartigimod IV over time
• To evaluate the PK of efgartigimod PH20 SC and efgartigimod IV
• To evaluate the safety, tolerability, and immunogenicity of efgartigimod PH20 SC and efgartigimod IV
• To evaluate the clinical efficacy of efgartigimod PH20 SC and efgartigimod IV

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Participants are eligible to be included in the study only if all of the following criteria apply:
1. Must be capable of giving signed informed consent as described in Section 10.1, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
2. At least 18 years of age at the time of signing the ICF.
3. Diagnosed with gMG with confirmed documentation and supported by at least 1 of the following:
a. History of abnormal neuromuscular transmission demonstrated by single fiber electromyography or repetitive nerve stimulation
b. History of positive edrophonium chloride test
c. Demonstrated improvement in MG signs upon treatment with oral acetylcholinesterase (AChE) inhibitors as assessed by the treating physician
4. Meeting the clinical criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, IVa, or IVb
5. Abdominal skin tissue allows for absorption and assessment of local safety of the planned SC injection, as determined by the investigator.
6. An MG-ADL total score of ≥5 points, with more than 50% of the score due to nonocular symptoms at screening and baseline.
7. Receiving a stable dose of other gMG treatment (concomitant gMG treatment) prior to screening. For patients receiving nonsteroidal immunosuppressants (NSIDs), steroids, and/or AChE inhibitors as concomitant medications, the following dose conditions apply:
a. NSIDs (eg, azathioprine, methotrexate, cyclosporine, tacrolimus, mycophenolate mofetil, and cyclophosphamide): treatment initiated at least 6 months prior to screening and no changes to dose in the 3 months before screening.
b. Steroids: treatment initiated at least 3 months prior to screening and no dose changes in the month before screening
c. AChE inhibitors: stable dose with no dose escalation during the 2 weeks before screening. AChE inhibitors must be withheld for at least 12 hours before the QMG assessment, to be consistent with the revised manual for the QMG test, as recommended by the MFGA.
8. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies and:
a. Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last study dose of the IMP:
− Refrain from donating sperm
Plus either
− Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent
Or
− Must agree to use a male condom with a female partner using an additionally highly effective contraceptive method with a failure rate of <1% per year as described in Section 10.5. when having sexual intercourse with a woman of childbearing potential who is not currently pregnant
Or
− Be a sterilized man who has had a documented absence of sperm post-procedure
b. Female participants are eligible to participate if they are not pregnant or breastfeeding, and they are 1 of the following:
− Women of non-childbearing potential (WONCBP), as defined in Section 10.5.1.
Or
− Women of childbearing potential (WOCBP) as defined in Section 10.5.1 and is using a contraceptive method that is highly effective (with a failure rate of <1% per year) during the study intervention and for at least 90 days after the last study dose of the IMP. The investigators should evaluate the potential for contraceptive method failure (eg, noncompliance) in relationship to the first dose of the study intervention
− WOCBP must have a negative highly sensitive serum pregnancy test within the screening period before the first dose of study IMP, see Section 8.2.8.
− Additional requirements for pregnancy testing during and after study intervention are located in Section 8.2.8.
− The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.

E.4

Principal exclusion criteria

Participants are excluded from the study if any of the following criteria apply:
1. Are pregnant or lactating, or intend to become pregnant during the study or within 90 days after the last dose of IMP.
2. Has any of the following medical conditions:
a. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening
b. 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
c. History of malignancy unless deemed cured by adequate treatment with no evidence of reoccurrence for ≥3 years before the first administration of the 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).
d. Clinical evidence of other significant serious diseases, or the participant has had a recent major surgery, or who have any other condition that, in the opinion of the investigator, could confound the results of the study or put the participant at undue risk.
3. Worsening muscle weakness secondary to concurrent infections or medications (aminoglycosides, beta-blockers, etc.)
4. A documented lack of clinical response to plasma exchange (PLEX)
5. Received a live-attenuated vaccine fewer than 28 days before screening. Receiving an inactivated subunit, polysaccharide, or conjugate vaccine any time before screening is not exclusionary.
6. Received a thymectomy <3 months prior to screening or one is planned to be performed during the study period.
7. 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 (https://www.cdc.gov/hepatitis/HBV/PDFs/SerologicChartv8.pdf, see Section 10.8)
− Hepatitis C virus (HCV) based on HCV antibody assay
− Human immunodeficiency virus (HIV) based on a CD4 count of <200 cells/mm3 or test results that are associated 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
b. Positive nasopharyngeal swab test for SARS-CoV-2
8. Using the following prior or concomitant therapies:
a. Use of an investigational product within 3 months or 5 half-lives (whichever is longer) before the first dose of IMP
b. Use of any monoclonal antibody within 6 months before the first dose of the IMP
c. Use of Ig administered intravenously (IVIg), SC (SCIg), or intramuscularly within 4 weeks of screening
d. Use of PLEX within 4 weeks of screening
e. Previously participated in a clinical study with efgartigimod and/or products co-formulated with rHuPH20 and received at least 1 administration of IMP
9. Total IgG levels <6 g/L at screening
10. Current or history of (ie, within 12 months of screening) alcohol, drug, or medication abuse
11. A known hypersensitivity reaction to efgartigimod, rHuPH20, or any of its excipients

E.5 End points

E.5.1

Primary end point(s)

• Percent reduction from baseline in total IgG levels at day 29, ie, 7 days after the fourth IV or SC administration

E.5.1.1

Timepoint(s) of evaluation of this end point

please refer to E.5.1

E.5.2

Secondary end point(s)

• Absolute values, change from baseline and percent reduction from baseline in total immunoglobulin (IgG) levels over time
• Absolute values, change from baseline and percent reduction from baseline in AChR-Ab levels over time in AChR- Ab positive patients
• Absolute values, change from baseline, and percent reduction from baseline in IgG subtype levels (IgG1, IgG2, IgG3, and IgG4) over time
• Area under the effect curve (AUEC) of the percentage reduction from baseline total IgG and similar AUEC for each IgG subtype per dosing interval (days 1–8, days 8–15, days 15–22, and days 22–29), days 1–29, and over the entire study (days 1–71)
• PK parameters: maximum concentration (Cmax) (after all doses for the IV treatment arm), concentration observed predose (Ctrough)
• Incidence and prevalence of anti-drug antibodies (ADAs) against efgartigimod
• Incidence and prevalence of ADAs against rHuPH20 in the SC treatment arm
• Incidence and severity of adverse events (AEs), incidence of serious adverse events (SAEs), and changes in laboratory test results, physical examination results, vital signs, and electrocardiogram (ECG) results
• Number and percentage of Myasthenia Gravis Activities of Daily Living (MG-ADL) responders
• Numbers and percentage of QMG responders
• Change from baseline in MG-ADL total score over time
• Change from baseline in QMG score over time

E.5.2.1

Timepoint(s) of evaluation of this end point

All the secondary endpoints are timeframe 'up to 12 weeks', except the 4th bullet 'area under the curve'.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Tolerability and Immunogenicity

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Bosnia and Herzegovina

Georgia

Japan

Russian Federation

Serbia

United States

Belgium

Germany

Hungary

Italy

Netherlands

Poland

Spain

United Kingdom

Czechia

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2020-12-29.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

110

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Roll over to long term safety study ARGX-113-2002

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-02-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-02-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-12-13

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IMP with orphan designation in the indication
Orphan Designation Number:
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