A Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of ARGX-113 in Patients With Myasthenia Gravis Who Have Generalized Muscle Weakness

NCT02965573 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: ARGX-113-16022016-002938-73
• Study Type: interventional
• Target: 24
• Locations: 8 countries
• Sites: 19

Brief 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.

Conditions

Myasthenia Gravis

Outcome Measures

Primary Outcomes (7)

• Number of Patients With Treatment Emergent Adverse Events (TEAES) and Treatment Emergent Serious Adverse Events (SAEs)

  TEAEs were defined as AEs that first occurred or worsened in severity after the first administration of the treatment. A treatment emergent SAE was any untoward medical occurrence that resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization;resulted in persistent or significant disability or incapacity; was a congenital abnormality or birth defect; or other medically significant events. All TEAEs observed were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 with descriptions of severity for each AE based on the following general guideline: Grade 1= mild; Grade 2 = moderate; Grade 3 = severe or medically significant but not immediately life-threatening; Grade 4 = life-threatening consequences; Grade 5 = death related to AE.

  Day 1 to Day 78

• Mean Change From Baseline in Vital Signs: Blood Pressure

  The patients' diastolic and systolic blood pressure were measured pre-dose on dosing days 1,8,15 and 22 and also during the follow up period. The mean change from baseline at each time point is presented. Baseline is defined as the last non-missing value before first dose of study medication.

  Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

• Mean Change From Baseline in Vital Signs: Heart Rate

  The patients' heart rate was measured pre-dose on dosing days 1,8,15 and 22 and also during the follow up period. The mean change from baseline at each time point is presented. Baseline is defined as the last non-missing value before first dose of study medication.

  Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

• Mean Change From Baseline in Vital Signs: Temperature

  The patients' temperature was measured pre-dose on dosing days 1,8,15 and 22 and also during the follow up period. The mean change from baseline at each time point is presented. Baseline is defined as the last non-missing value before first dose of study medication.

  Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

• Mean Change From Baseline in Vital Signs: Weight

  The patients' weight as measured pre-dose on dosing days 1,8,15 and 22 and also during the follow up period. The mean change from baseline at each time point is presented. Baseline is defined as the last non-missing value before first dose of study medication.

  Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

• Number of Patients With Abnormal Clinically Relevant Findings in Electrocardiogram (ECG) Parameters

  ECG parameters of heart rate, PR, QT, and QRS interval were read locally and performed pre-dose on dosing days 1,8,15 and 22 and on the last follow up visit on Day 78. Any patients recording abnormal clinically relevant findings during the study are presented.

  Day 1 to Day 78

• Number of Patients With Abnormal Clinical Laboratory Findings Reported as TEAEs

  Sampling for clinical laboratory tests including hematology, clinical chemistry, and urinalysiswas performed pre-dose on dosing Days 1, 8, 15 and 22 and throughout the follow up period. Patients fasted for at least 8 hours prior to this sampling. Abnormal laboratory values, or test results were not reported as TEAEs unless they were associated with clinical signs and symptoms that were considered clinically relevant, required therapy or led to treatment discontinuation. Patients reporting TEAEs in any of the laboratory parameters during the study are presented.

  Day 1 to Day 78

Secondary Outcomes (15)

• Mean Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score

  Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

• Mean Change From Baseline in QMG Score

  Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

• Mean Change From Baseline in MGC Score

  Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

• Mean Change From Baseline in MGQoL15r Score

  Baseline and Days 8,15, 22, 29, 36, 43, 50, 64 and 78

• Maximum Reduction From Baseline in MG-ADL Score

  Day 1 to Day 78

Study Arms (2)

ARGX-113

ACTIVE COMPARATOR

During the Treatment period, eligible patients will be randomized at a 1:1 ratio to receive ARGX-113

Biological: ARGX-113

Placebo

PLACEBO COMPARATOR

During the Treatment period, eligible patients will be randomized at a 1:1 ratio to receive placebo

Drug: Placebo

Interventions

ARGX-113 BIOLOGICAL

ARGX-113

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 \[diaphragm or cervical/vault caps\]) and should have been stable on their hormonal contraceptive treatment for at least 4 weeks before Screening.

You may not qualify if:

• Females who are pregnant or lactating.
• MGFA Class I, IVb, and V.
• Have an active infection, a recent serious infection (i.e., requiring injectable antimicrobial therapy or hospitalization) within the 8 weeks prior to Screening; or history of or known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or Mycobacterium tuberculosis. Patients must have negative test results for HBV surface antigen, HBV core antibody, HCV antibody, HIV 1 and 2 antibodies, and a negative QuantiFERON®-TB Gold test at Screening. Patients with an indeterminate QuantiFERON®-TB Gold test result will be allowed one retest; if not negative on retesting, the patient will be excluded.
• At Screening, have clinically significant laboratory abnormalities or as below:
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \> 2 x upper limit of normal (ULN).
• Total serum bilirubin of \> 1.5 x ULN (except for Grade 1 hyperbilirubinemia solely due to a medical diagnosis of Gilbert's syndrome).
• Serum creatinine \> 1.5 mg/dL and creatinine clearance \< 50 ml/min (using the Chronic Kidney Disease Epidemiology \[CKD-EPI\]-Creatinine formula).
• Clinically Significant proteinuria (i.e., \> 3 x ULN).
• Hemoglobin ≤ 9 g/L.
• Thyroid stimulating hormone or thyroglobulin outside of the central laboratory normal range.
• International normalized ratio (INR) or activated partial thromboplastin time (aPTT) \> 1.2 x ULN.
• Total immunoglobulin G level \< 6 g/L.
• Body Mass Index (BMI) at Screening ≥ 35 kg/m2.
• Use of rituximab, belimumab, eculizumab or any monoclonal antibody for immunomodulation within 6 months prior to first dosing. Patients with prior exposure to rituximab must have CD19 counts within the normal range per the central laboratory at Screening.
• Use of any biological therapy or investigational drug within 3 months or 5 half-lives of the drug (whichever is longer) before Screening.

Sponsors & Collaborators

• argenx: lead
• Quintiles, Inc.: collaborator

Study Sites (19)

Investigator Site 19

Irvine, California, United States

Location

Investigator Site 17

Los Angeles, California, United States

Location

Investigator Site 15

Tampa, Florida, United States

Location

Investigator Site 16

Indianapolis, Indiana, United States

Location

Investigator Site 14

Chapel Hill, North Carolina, United States

Location

Investigator Site 18

Dublin, Ohio, United States

Location

Investigator Site 2

Ghent, Belgium

Location

Investigator Site 1

Leuven, Belgium

Location

Investigator Site 4

Montreal, Canada

Location

Investigator Site 3

Toronto, Canada

Location

Investigator Site 7

Bergamo, Italy

Location

Investigator Site 6

Milan, Italy

Location

Investigator Site 5

Roma, Italy

Location

Investigator Site 8

Leiden, Netherlands

Location

Investigator Site 10

Gdansk, Poland

Location

Investigator Site 9

Krakow, Poland

Location

Investigator Site 12

Barcelona, Spain

Location

Investigator Site 11

Madrid, Spain

Location

Investigator Site 13

Solna, Sweden

Location

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

efgartigimod alfa

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Regulatory Manager
• Organization: argenx BVBA

regulatory@argenx.com

+32 93103400

Study Officials

• Antonio Guglietta, MD

  argenx

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2016
• First Posted: November 17, 2016
• Study Start: December 30, 2016
• Primary Completion: October 20, 2017
• Study Completion: October 20, 2017
• Last Updated: August 28, 2024
• Results First Posted: January 8, 2021

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); CA (2); IT (3); ES (2); PL (2); BE (2); NL (1); SE (1)