E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Generalized Myasthenia Gravis (gMG) |
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E.1.1.1 | Medical condition in easily understood language |
Generalized Myasthenia Gravis (gMG) |
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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 |
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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 assess the clinical efficacy of efgartigimod IV 10 mg/kg administered in a q2w continuous regimen compared to that administered in a cyclic regimen |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety and tolerability of both treatment regimens used throughout the study
• To assess the clinical efficacy of efgartigimod IV in both treatment regimens over time
• To compare the number of participants who achieve maximal clinical effect during different treatment regimens |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Capable of giving signed informed consent as described in Section 10.1.3 of the protocol, 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
3. Diagnosed with gMG with confirmed documentation and supported by a physical exam and confirmed seropositivity for AChR-Abs by the central laboratory. During the screening or rescreening period, any historical results for AChR-Ab can be used, as long as the results are ≤ 1 year old.
4. Meets the clinical criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, or IV
5. Has an MG-ADL total score ≥5 at screening and the day 1 visit, with more than 50% of the score due to nonocular symptoms
6. Concomitant gMG treatment is permitted. Permitted concomitant gMG treatment includes nonsteroidal immunosuppressive drugs (NSIDs), steroids, and/or acetylcholinesterase AChE inhibitors. If receiving corticosteroids and/or NSIDs, must be on a stable dose for at least 1 month before screening.
7. Agrees to use contraceptive measures consistent with local regulations and the following:
a. Male participants: (contraceptive measures provided in Section 10.4.2.2 of the protocol, refer to Section 10.7 of the protocol for country-specific requirements)
b. WOCBP (defined in Section 10.4.1 of the protocol) must have a negative serum pregnancy test at screening and a negative urine pregnancy test at baseline before receiving IMP (Section 10.4.2.1. of the protocol, see Section 10.7 of the protocol for country-specific requirements) |
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E.4 | Principal exclusion criteria |
1. Clinically significant uncontrolled active or chronic bacterial, viral, or fungal infection at screening that is not sufficiently resolved in the investigator's opinion
2. A positive test for SARS-CoV-2 at screening
3. Any other known autoimmune disease that, in the opinion of the investigator, would interfere with an accurate assessment of the clinical symptoms of gMG and/or put the participant at undue risk
4. 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, provided they are adequately treated at screening:
a. Basal cell or squamous cell skin cancer
b. Carcinoma in situ of the cervix
c. Carcinoma in situ of the breast
d. Incidental histological finding of prostate cancer (TNM stage T1a or T1b)
5. Clinical evidence of other significant serious diseases, a recent (<3 months) major surgery, or any other condition that, in the opinion of the investigator, could confound the results of the study or put the participant at undue risk
6. A thymectomy within 3 months of screening
7. Pregnant or lactating females and those who intend to become pregnant during the study or within 90 days of the last dose of IMP
8. Use of the following prior or concomitant therapies:
a. IVIg or subcutaneous (SC)Ig within 14 days of day 1
b. Rituximab within 6 months of day 1
c. Eculizumab within 1 month of day 1
d. Other monoclonal antibodies (eg, adalimumab, tocilizumab, ixekizumab) within 5 half-lives of the monoclonal antibodies before day 1
e. Use of any other investigational product within 3 months or 5 half-lives, whichever is longer, before day 1
f. Receipt of a live or live-attenuated vaccine within 4 weeks of screening. The receipt of any inactivated, subunit, polysaccharide, conjugate vaccine at any time before screening is not considered exclusionary.
9. Previous participation in a clinical study or patient access program during which they were treated with efgartigimod
10. Positive serum test at screening for an active viral infection with any of the following conditions:
a. Hepatitis B virus (HBV) that is indictive of an acute or chronic infection
b. Hepatitis C virus (HCV) based on HCV antibody assay (unless associated with a negative HCV RNA test)
c. HIV based on test results that are associated with an AIDS-defining condition or a CD4 count ≤200 cells/mm3
11. Total IgG <6 g/L at screening
12. Known hypersensitivity reaction to efgartigimod or any of its excipients
13. The participant stands in any relationship of dependency with the sponsor.
14. The participant has been institutionalized due to an official or judicial order. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean of the average MG-ADL total score change from baseline during the visit of week (W)1 through W21 by regimen arm |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1: Incidence and severity of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESIs) Time point: 126 weeks
2: Incidence of serious adverse events (SAEs) and AEs of special interest (AESIs) Time point: 126 weeks
3: Change from baseline in the Myasthenia Gravis – Activities of Daily Living (MG-ADL) total score over time. A higher total score indicates more impairment. Time point: 128 weeks
4: Normalized area under the effect curve (AUEC) of MG-ADL total score improvement from baseline during following intervals: Day 1 through Week7, Week 7 through Week 14, Week 14 trough Week 21 and Week 7 through Week 21. Time point: 21 weeks
5: Characterization of MG-ADL total score change from baseline during the following 5 intervals using mean and standard deviation: Week 1 through Week 7, Week 8 through Week 14, Week 15 through Week 21, Week 8 through Week 21 and Week 1 through Week 21. Time point: 21 weeks
6: Number of participants who have a ≥2, 3, 4, or 5 points improvement in MG-ADL total score from baseline. during the following 5 intervals: Week 1 through Week 7, Week 8 through Week 14, Week 15 through Week 21, Week 8 through Week 21 and Week 1 through Week 21. Time point: 21 weeks
7: percentage of participants who have a ≥2, 3, 4, or 5 points improvement in MG-ADL total score from baseline during the following 5 intervals: Week 1 through Week 7, Week 8 through Week 14, Week 15 through Week 21, Week 8 through Week 21 and Week 1 through Week 21. Time point: 21 weeks
8: Percentage of time, participants have a change in MG-ADL total score of at least 2 points from baseline during Week 4 through Week 21. Time point: 21 weeks
9: Number of participants who achieve minimal symptom expression (MSE), defined as a MG-ADL total score of 0 or 1. Time point: 21 weeks
10: Percentage of participants who achieve minimal symptom expression (MSE), defined as a MG-ADL total score of 0 or 1 in the following 5 intervals: Week 1 through Week 7, Week 8 through Week 14, Week 15 through Week 21, Week 8 through Week 21 and Week 1 through Week 21. Time point: 21 weeks
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Please refer individual end points mentioned in above section. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
immunogenicity and tolerability |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
efgartigimod administered in a continuous regimen vs efgartigimod in a cyclic regimen |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
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 | No |
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 |
Canada |
Georgia |
United Kingdom |
United States |
Austria |
Belgium |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
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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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |