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

Sponsor
argenx (Industry)
Overall Status
Completed
CT.gov ID
NCT04735432
Collaborator
(none)
111
Enrollment
47
Locations
2
Arms
10.2
Actual Duration (Months)
2.4
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the Pharmacodynamics (PD), Pharmacokinetics (PK), safety, tolerability, immunogenicity, and clinical efficacy of efgartigimod coformulated with recombinant human hyaluronidase PH20 (rHuPH20) as compared to efgartigimod IV infused in patients with generalized myasthenia gravis (gMG). The study duration is approximately 12 weeks. After screening, patients will be randomized to receive either efgartigimod infusions or efgartigimod PH20 subcutaneously (SC)

Condition or Disease Intervention/Treatment Phase
  • Biological: efgartigimod PH20 SC
  • Biological: efgartigimod IV
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
111 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Feb 5, 2021
Actual Primary Completion Date :
Nov 2, 2021
Actual Study Completion Date :
Dec 13, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: efgartigimod PH20 SC

Patients receiving efgartigimod PH20 subcutaneous (SC) treatment

Biological: efgartigimod PH20 SC
Subcutaneous injection with efgartigimod PH20 SC
Experimental: efgartigimod

Patients receiving efgartigimod intravenous (IV) treatment

Biological: efgartigimod IV
Intravenous infusion of efgartigimod

Outcome Measures

Primary Outcome Measures

  1. Percent change from baseline in total Immunoglobulin (IgG) levels at day 29 [at day 29]

Secondary Outcome Measures

  1. Absolute values in total immunoglobulin (IgG) levels over time [up to 12 weeks]

  2. Change from baseline in total immunoglobulin (IgG) levels over time [up to 12 weeks]

  3. Percent change from baseline in total immunoglobulin (IgG) levels over time [up to 12 weeks]

  4. Absolute values in acetylcholine receptor binding autoantibodies (AChR-Ab) levels over time in AChR-Ab positive patients [up to 12 weeks]

  5. Change from baseline in acetylcholine receptor binding autoantibodies (AChR-Ab) levels over time in AChR-Ab positive patients [up to 12 weeks]

  6. Percent change from baseline in acetylcholine receptor binding autoantibodies (AChR-Ab) levels over time in AChR-Ab positive patients [up to 12 weeks]

  7. Absolute values in immunoglobulin IgG subtype levels (IgG1, IgG2, IgG3, and IgG4) over time [up to 12 weeks]

  8. Change from baseline in immunoglobulin IgG subtype levels (IgG1, IgG2, IgG3, and IgG4) over time [up to 12 weeks]

  9. Percent change from baseline in immunoglobulin IgG subtype levels (IgG1, IgG2, IgG3, and IgG4) over time [up to 12 weeks]

  10. Area under the effect curve (AUEC) of the percentage change from baseline total immunoglobulin G [up to 12 weeks]

  11. Similar Area under the effect curve (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) [up to 12 weeks]

  12. Pharmacokinetics (PK) parameters: maximum concentration (Cmax) (after all doses for the IV treatment arm) [up to 12 weeks]

  13. Pharmacokinetics (PK) parameters: concentration observed predose (Ctrough) [up to 12 weeks]

  14. Incidence of anti-drug antibodies (ADAs) against efgartigimod [up to 12 weeks]

  15. Prevalence of anti-drug antibodies (ADAs) against efgartigimod [up to 12 weeks]

  16. Incidence of anti-drug antibodies (ADAs) against rHuPH20 in the SC treatment arm [up to 12 weeks]

  17. Prevalence of anti-drug antibodies (ADAs) against rHuPH20 in the SC treatment [up to 12 weeks]

  18. Incidence of adverse events (AEs) and serious adverse events (SAEs) [up to 12 weeks]

  19. Severity of adverse events (AEs) [up to 12 weeks]

  20. Number of Myasthenia Gravis Activities of Daily Living (MG-ADL) responders [up to 12 weeks]

  21. Percentage of Myasthenia Gravis Activities of Daily Living (MG-ADL) responders [up to 12 weeks]

  22. Number of Quantitative Myasthenia Gravis (QMG) responders [up to 12 weeks]

  23. Percentage of Quantitative Myasthenia Gravis (QMG) responders [up to 12 weeks]

  24. Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) total score over time. A higher total score indicates more impairment. [up to 12 weeks]

  25. Change from baseline in Quantitative Myasthenia Gravis (QMG) score over time. A higher total score indicates more severe impairment [up to 12 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
Bullet list of each inclusion criterium:

  1. Must be capable of giving signed informed consent, 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 informed consent form.

  3. Diagnosed with generalized Myasthenia Gravis (gMG) with confirmed documentation and supported by at least 1 of the following:

  4. History of abnormal neuromuscular transmission demonstrated by single fiber electromyography or repetitive nerve stimulation

  5. History of positive edrophonium chloride test

  6. Demonstrated improvement in Myasthenia Gravis (MG) signs upon treatment with oral acetylcholinesterase (AChE) inhibitors as assessed by the treating physician

  7. Meeting the clinical criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, IVa, or IVb

Exclusion Criteria:
Bullet list of each exclusion criterium:

  1. Are pregnant or lactating, or intend to become pregnant during the study or within 90 days after the last dose of Investigational Medicinal Product.

  2. Has any of the following medical conditions:

  3. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening

  4. 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.

  5. 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).

  1. 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Investigator site 2 - US0010032 Carlsbad California United States 92011
2 Investigator Site 41 - US0010004 Orange California United States 92868
3 Investigator site 2 - US0010108 Boca Raton Florida United States 33428
4 Investigator site 1 - US0010110 Port Charlotte Florida United States 33952
5 Investigator Site 27 - US0010006 Tampa Florida United States 41076
6 Investigator Site 47 - US0010113 Augusta Georgia United States 30912
7 Investigator Site 42 - US0010015 Kansas City Kansas United States 66205
8 Investigator Site 11 - US0010111 Amherst New York United States 14226
9 Investigator Site 40 - US0010003 Chapel Hill North Carolina United States 27514
10 Investigator Site 38 - US0010077 Durham North Carolina United States 27710
11 Investigator Site 43 - 0010019 Cleveland Ohio United States 44195
12 Investigator site 4 - US0010008 Cordova Tennessee United States 38018
13 Investigator Site 28 - US0010066 Austin Texas United States 78756
14 Investigator Site 46 - US0010009 Texas City Texas United States 78229
15 Investigator site 5 - BE0320007 Gent East-Flanders Belgium 9000
16 Investigator site 13 - GE9950002 Tbilisi Georgia 0112
17 Investigator site 12 - GE9950001 Tbilisi Georgia 0114
18 Investigator site 14 - GE9950003 Tbilisi Georgia 0114
19 Investigator Site 44 - GE9950004 Tbilisi Georgia 0160
20 Investigator Site 45 - GE9950016 Tbilisi Georgia 0160
21 Investigator Site 30 - DE490006 Berlin Germany 10117
22 Investigator Site 29 - DE490009 Münster Germany 48149
23 Investigator site 15 - HU0360013 Budapest Hungary 1082
24 Investigator Site 16 - HU0360020 Debrecen Hungary 4032
25 Investigator Site 17 - IT0390003 Milan Italy 20133
26 Investigator Site 39 - IT0390008 Roma Italy 00189
27 Investigator Site 31 - JP0810055 Sapporo Hokkaido Japan 063-0005
28 Investigator Site 18 - JP0810002 Chiba Japan 260-8677
29 Investigator site 6 - JPN0810004 Hanamaki Japan 025-0082
30 Investigator Site 33 - JP0810058 Hiroshima Japan 0810058
31 Investigator Site 19 - JP0810007 Osaka Japan 565-0871
32 Investigator Site 34 - JP0810005 Sendai Japan 983-8520
33 Investigator Site 32 - JP0810059 Tokyo Japan 143-8541
34 Investigator Site 20 - JP0810009 Tokyo Japan 160-0023
35 Investigator Site 7 - NL0310001 Leiden Netherlands 2333
36 Investigator Site 21 - PL0480001 Gdańsk Poland 80-952
37 Investigator Site 8 - PL0480007 Katowice Poland 40-123
38 Investigator Site 9 - PL0480024 Kraków Poland 31-2002
39 Investigator Site 22 - PL0480005 Kraków Poland 31-505
40 Investigator Site 23 - PL0480018 Lublin Poland 20-093
41 Investigator Site 24 - PL0480022 Warsaw Poland 02-097
42 Investigator Site 35 - RU0070002 Novosibirsk Russian Federation 630087
43 Investigator Site 36 - RU0070014 Saint Petersburg Russian Federation 194354
44 Investigator Site 37 - ES0340021 Barcelona Spain 08035
45 Investigator Site 26 - ES0340038 Barcelona Spain 08041
46 Investigator Site 25 - ES0340002 Madrid Spain 28046
47 Investigator Site 10 - ES0340039 Valencia Spain 46026

Sponsors and Collaborators

  • argenx

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
argenx
ClinicalTrials.gov Identifier:
NCT04735432
Other Study ID Numbers:
  • ARGX-113-2001
First Posted:
Feb 3, 2021
Last Update Posted:
Feb 1, 2022
Last Verified:
Jan 1, 2022
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Product Manufactured in and Exported from the U.S.:
No
Additional relevant MeSH terms:
Myasthenia Gravis
Muscle Weakness

Study Results

No Results Posted as of Feb 1, 2022