Phase 2
N=24
A Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of ARGX-113 in Patients With Myasthenia Gravis Who Have Generalized Muscle Weakness
Myasthenia Gravis
Bottom Line
View on ClinicalTrials.gov: NCT02965573 ↗Enrolled (actual)
24
Serious AEs
0.0%
Results posted
Jan 2021
Primary outcome: Primary: Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) — 10; 10; 8; 3 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- ARGX-113 (Biological); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- argenx
- Primary completion
- Oct 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs) |
10; 10; 8; 3; 0; 0 | — |
| PRIMARY Mean Change From Baseline in Vital Signs: Blood Pressure |
3.8; 6.3; 4.5; 2.7; 2.7; 3.0 | — |
| PRIMARY Mean Change From Baseline in Vital Signs: Heart Rate |
-2.7; 1.8; -4.1; 2.5; -0.8; -1.1 | — |
| PRIMARY Mean Change From Baseline in Vital Signs: Temperature |
0.18; 0.15; 0.09; 0.16; 0.05; 0.27 | — |
| PRIMARY Mean Change From Baseline in Vital Signs: Weight |
0.18; -0.02; 0.60; 0.31; 0.54; 0.01 | — |
| PRIMARY Number of Patients With Abnormal Clinically Relevant Findings in Electrocardiogram (ECG) Parameters |
0; 0 | — |
| PRIMARY Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs |
2; 0; 1; 0; 2; 0 | — |
| SECONDARY Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score |
-1.9; -0.7; -2.8; -2.2; -3.5; -2.5 | — |
| SECONDARY Mean Change From Baseline in QMG Score |
-2.8; 0.0; -4.0; -1.8; -4.0; -1.8 | — |
| SECONDARY Mean Change From Baseline in MGC Score |
-4.3; -1.3; -5.8; -4.4; -7.8; -4.0 | — |
| SECONDARY Mean Change From Baseline in MGQoL15r Score |
-2.0; -0.8; -3.7; -1.0; -4.3; -1.5 | — |
| SECONDARY Maximum Reduction From Baseline in MG-ADL Score |
-5.1; -3.7 | — |
| SECONDARY Maximum Reduction From Baseline in QMG Score |
-7.3; -4.3 | — |
| SECONDARY Maximum Reduction From Baseline in MGC Score |
-11.5; -7.7 | — |
| SECONDARY Maximum Reduction From Baseline in MGQoL15r Score |
-7.2; -3.0 | — |
| SECONDARY Pharmacokinetic (PK) Parameters - Plasma Concentrations of ARGX-113 |
179063.7; 173960.4; 153257.2; 162655.6; 7266.2; 9894.8 | — |
| SECONDARY PK Parameters - Median Time of Occurrence of Cmax (Tmax) of ARGX-113 |
2.44; 2.50; 2.50; 2.46 | — |
| SECONDARY PK Parameters - Apparent Terminal Half-life (t1/2 Lambda z) of ARGX-113 |
116.08 | — |
| SECONDARY PK Parameters - Accumulation Ratio (Rac) of ARGX-113 |
0.9360 | — |
| SECONDARY Mean Percent Change From Baseline in Immunoglobulins (IgGs) |
-70.0; -2.8; -20.4; 6.4; -65.5; -2.1 | — |
| SECONDARY Mean Percent Change From Baseline in Anti-Acetylcholine Receptor (AChR) Antibodies |
-52.2686; -0.3236; -1.3361; -7.8881 | — |
| SECONDARY Number of Patients With an Anti-drug Antibodies (ADA) Response |
4; 2; 4; 3 | — |
Summary
This is a randomized, double-blind, placebo-controlled, multicenter Phase II study to evaluate the safety, efficacy, and pharmacokinetics of ARGX-113 for the treatment of autoimmune Myasthenia Gravis (MG) with generalized muscle weakness.
Eligibility Criteria
Inclusion Criteria
- Have the ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information), and comply with the study protocol procedures (including required study visits).
- Male or female patients aged ≥18 years.
- Diagnosis of autoimmune MG with generalized muscle weakness meeting the clinical criteria for diagnosis of MG as defined by the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II, III, or IVa, and likely not in need of a respirator for the duration of the study as judged by the Investigator.
The confirmation of the diagnosis should be documented and supported by:
- Positive serologic test for anti-AChR antibodies before Screening and
- at least 1 of the following 3 tests: (i) History of abnormal neuromuscular transmission test demonstrated by single-fiber electromyography or repetitive nerve stimulation or (ii) History of positive edrophonium chloride test, or (iii) Patient has demonstrated improvement in MG signs on oral cholinesterase inhibitors as assessed by the treating physician.
- A total score of ≥ 5 on the MG ADL at Screening and Baseline with more than 50% of this score attributed to non ocular items.
- Patients are required to be on a stable dose of their MG treatment prior to randomization. For patients receiving AZA, other NSIDs, steroids, and/or cholinesterase inhibitors as concomitant medications the following conditions will apply:
- AZA: treatment initiated at least 12 months ago and no dose changes in the last 6 months before screening.
- Other NSIDs (e.g., methotrexate, cyclosporine, tacrolimus, mycophenolate mofetil, and cyclophosphamide) treatment initiated at least 6 months ago and no dose changes in the last 3 months before Screening.
- Steroids treatment initiated at least 3 months prior to and no dose changes in the last month before Screening.
- Cholinesterase inhibitors: to be on a stable dose for >2 weeks before Screening.
Note: cholinesterase inhibitors must be held for at least 12 hours consistent with the revised manual for the QMG test as recommended by the Myasthenia Gravis Foundation of America Inc (MGFA), before the MGQoL15r, MG-ADL, QMG, and MGC assessments.
- Females of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test at Visit 1 prior to administration of IMP. Female of childbearing potential are defined as all female participants unless they are postmenopausal (defined by continuous amenorrhea) for at least 2 years with a Follicle stimulating hormone (FSH) > 40 IU/L or are surgically sterile (i.e., who had a hysterectomy, bilateral oophorectomy, or have current documented tubal ligation or any other permanent female sterilization procedure). Determination of FSH levels can be used to confirm postmenopausal status in amenorrheic patients not on hormonal replacement therapy if the test result is within the postmenopausal range per the central laboratory.
- Female participants of childbearing potential must agree to use a highly effective method of contraception (i.e., pregnancy rate of less than 1% per year) during the study and for 90 days after the discontinuation of the IMP. Adequate contraceptive methods include combined hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine devices (IUDs), intrauterine hormone-releasing system (IUS), true sexual abstinence (when this is in line with the preferred and usual lifestyle of the participant), bilateral tubal occlusion, or a female participant who is not of childbearing potential. Female participants and female partners of male study participants using a hormonal contraceptive must also use a barrier method (i.e., condom or occlusive cap [diaphragm or
Data sourced from ClinicalTrials.gov (NCT02965573). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.