An Efficacy and Safety Study of ARGX-113 in Patients With Myasthenia Gravis Who Have Generalized Muscle Weakness (ADAPT)

• ClinicalTrials.gov Identifier: NCT03669588
• Recruitment Status: Completed
• First Posted: September 13, 2018
• Results First Posted: February 8, 2022
• Last Update Posted: February 8, 2022
• Sponsor: argenx
• Information provided by (Responsible Party): argenx

Tracking Information

• First Submitted Date: September 6, 2018
• First Posted Date: September 13, 2018
• Results First Submitted Date: January 14, 2022
• Results First Posted Date: February 8, 2022
• Last Update Posted Date: February 8, 2022
• Actual Study Start Date: August 22, 2018
• Actual Primary Completion Date: April 6, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 14, 2022)

Percentage of MG-ADL Responders During Cycle 1 (C1); Analyzed in the AChR-Ab Seropositive Population [ Time Frame: Baseline up to Day 63 (end of TC1) ]

The MG-ADL is an 8-item patient-reported scale to assess MG symptoms and their effects on daily activities. The scale comprises 2 items on daily life activities and 6 items on symptoms. The MG-ADL total score range is 0-24, with higher scores indicative of greater disease severity. A patient was considered an MG-ADL responder during C1 if there was a reduction of ≥2 points on the MG-ADL total score (compared to baseline of C1 [C1B]) for ≥4 consecutive weeks with the first reduction occurring no later than 1 week after the last infusion of IMP in C1.

• Original Primary Outcome Measures (submitted: September 11, 2018): Efficacy of ARGX-113 as assessed by the percentage of "Myasthenia Gravis Activities of Daily Living (MG-ADL) responders" in the acetylcholine receptor (AChR)-antibody (Ab) seropositive population [ Time Frame: Week 8 ]

Current Secondary Outcome Measures (submitted: January 14, 2022)

• Percentage of Quantitative Myasthenia Gravis (QMG) Responders During C1; Analyzed in the AChR-Ab Seropositive Population [ Time Frame: Baseline up to Day 63 (end of TC1) ]
  The QMG scale quantifies disease severity based on impairments of body functions and structures as defined by the International Classification of Disability and Health. The QMG scale consists of 13 items that measure endurance or fatigability, and accounts for fluctuations in disease state. The QMG total score range is 0-39, with higher scores indicative of greater disease severity. A patient was considered a QMG responder during C1 if there was a reduction of ≥3-points on the QMG total score (compared to C1B) for ≥4 consecutive weeks with the first reduction occurring no later than 1 week after the last infusion of IMP in C1.
• Percentage of MG-ADL Responders During C1; Analyzed in the Overall Population [ Time Frame: Baseline up to Day 63 (end of TC1) ]
  The percentage of MG-ADL responders during C1 in the overall population is reported for this secondary end point; percentage of MG-ADL responders during C1 in the AChR-Ab seropositive population is reported previously as a primary end point.
• Percentage of Time That Patients Had a Clinically Meaningful Improvement (CMI) in MG-ADL Total Score up to and Including Day 126; Analyzed in the AChR-Ab Seropositive Population [ Time Frame: Baseline up to Day 126 ]
  An MG-ADL CMI was defined as a reduction of ≥2 points on the total MG-ADL score compared to study entry baseline (SEB).
• Time From Week 4 to Qualify for Retreatment; Analyzed in the AChR-Ab Seropositive Population [ Time Frame: Week 4 up to Day 182 (end of study [EoS]) ]
  Time to qualify for retreatment was defined as time from the Week 4 assessment until the first visit with a <2-point reduction compared to SEB in the MG-ADL total score and MG-ADL total score ≥5 points with >50% of the total score attributable to nonocular symptoms.
• Percentage of Early MG-ADL Responders During C1; Analyzed in the AChR-Ab Seropositive Population [ Time Frame: Baseline up to Day 63 (end of TC1) ]
  A patient was considered an early MG-ADL responder during C1 if there was a reduction of ≥2 points on the MG-ADL total score (compared to C1B) for ≥4 consecutive weeks with the first reduction occurring no later than Week 2 (ie, after 1 or maximum 2 infusions of IMP in C1).

Original Secondary Outcome Measures (submitted: September 11, 2018)

• Efficacy of ARGX-113 as assessed by the percentage of "Quantitative Myasthenia Gravis (QMG) responders" in the AChR-Ab seropositive population. [ Time Frame: Week 8 ]
• Efficacy of ARGX-113 as assessed by the percentage of "MG-ADL responders" in the overall population (AChR-Ab seropositive and AChR-Ab seronegative patients). [ Time Frame: Week 8 ]
• Efficacy of ARGX-113 as assessed by the percentage of time that patients show a "clinically meaningful improvement" in total MG-ADL score during the trial in the AChR-Ab seropositive population [ Time Frame: Through study completion, an average of 26 weeks ]
• Duration of response [ Time Frame: Through study completion, an average of 26 weeks ]
• Onset of efficacy of ARGX-113 as assessed by the percentage of "early MG-ADL responders" in the AChR-Ab seropositive population. [ Time Frame: Up to Week 8 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: An Efficacy and Safety Study of ARGX-113 in Patients With Myasthenia Gravis Who Have Generalized Muscle Weakness
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Phase 3 Trial to Evaluate the Efficacy, Safety and Tolerability of ARGX-113 in Patients With Myasthenia Gravis Having Generalized Muscle Weakness
• Brief Summary: A randomized, double-blind, placebo controlled, multicenter Phase 3 trial to evaluate the efficacy, safety, tolerability, quality of life and impact on normal daily activities of ARGX-113 in patients with gMG.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Generalized Myasthenia Gravis

Intervention

• Biological: ARGX-113
  Intravenous administration of ARGX-113
  Other Name: efgartigimod
• Biological: Placebo
  Intravenous administration of placebo

Study Arms

• Experimental: ARGX-113
  Intervention: Biological: ARGX-113
• Placebo Comparator: Placebo
  Intervention: Biological: Placebo

• Publications *: Howard JF Jr, Bril V, Vu T, Karam C, Peric S, Margania T, Murai H, Bilinska M, Shakarishvili R, Smilowski M, Guglietta A, Ulrichts P, Vangeneugden T, Utsugisawa K, Verschuuren J, Mantegazza R; ADAPT Investigator Study Group. Safety, efficacy, and tolerability of efgartigimod in patients with generalised myasthenia gravis (ADAPT): a multicentre, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2021 Jul;20(7):526-536. doi: 10.1016/S1474-4422(21)00159-9. Erratum In: Lancet Neurol. 2021 Aug;20(8):e5.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 23, 2020): 167
• Original Estimated Enrollment (submitted: September 11, 2018): 150
• Actual Study Completion Date: April 6, 2020
• Actual Primary Completion Date: April 6, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Patients with the ability to understand the requirements of the trial, provide written informed consent, and comply with the trial protocol procedures.
2. Male or female patients aged ≥ 18 years.
3. Diagnosis of MG with generalized muscle weakness meeting the clinical criteria for diagnosis of MG as defined by the Myasthenia Gravis Foundation of America (MGFA) class II, III, IVa and IVb.

Other, more specific inclusion criteria are defined in the protocol

Exclusion Criteria:

1. Pregnant and lactating women, and those intending to become pregnant during the trial or within 90 days after the last dosing.
2. Male patients who are sexually active and do not intend to use effective methods of contraception during the trial or within 90 days after the last dosing or male patients who plan to donate sperm during the trial or within 90 days after the last dosing.
3. MGFA Class I and V patients.
4. Patients with worsening muscle weakness secondary to concurrent infections or medications.

5. Patients with known seropositivity or who test positive for an active viral infection at Screening with:

   • Hepatitis B Virus (HBV) (except patients who are seropositive because of HBV vaccination)
   • Hepatitis C Virus (HCV)
   • Human Immunodeficiency Virus (HIV)

Other, more specific exclusion criteria are further defined in the protocol.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Canada, Czechia, Denmark, France, Georgia, Germany, Hungary, Italy, Japan, Netherlands, Poland, Russian Federation, Serbia, United Kingdom, United States

Administrative Information

• NCT Number: NCT03669588
• Other Study ID Numbers: ARGX-113-1704; 2018-002132-25 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: argenx
• Original Responsible Party: Same as current
• Current Study Sponsor: argenx
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Antonio Guglietta, MD; argenx

• PRS Account: argenx
• Verification Date: March 2021