Trial Outcomes & Findings for Open Label Study of Subcutaneous Immunoglobulin (SCIg) in Myasthenia Gravis (NCT NCT02100969)

NCT ID: NCT02100969

Last Updated: 2021-06-02

Results Overview

The QMG is a 13 item ordinal scale which measures ocular, bulbar, extremity fatigue and strength, along with respiratory function. The scale is from 0 - 3 for each item, with 0 meaning normal and 3 is severe. Total score can range from 0 to 39. Change in MG severity will be measured using the Quantitative Myasthenia Gravis (QMG) Score for Disease severity. The QMG is a validated clinical composite scale. As mentioned in the protocol, our hypotheses are: H0: Proportion of patients whose QMG scores are increased by more than 3 points at the end of the SCIg treatment phase ≤ 0.65 HA: Proportion of patients whose QMG scores are increased by no more than 3 points at the end of the SCIg treatment phase \> 0.65 Thus, analysis of the primary outcome is done as a one-sample Z test of proportions. That is, the QMG is a continuous outcome, but analyses results are reported as proportions.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 23 participants
• Primary outcome timeframe: Change from Baseline to Week 12
• Results posted on: 2021-06-02

Participant Flow

North American study involving 5 sites (4 in the US and 1 in Canada). Subjects were recruited through clinical practice and advertisement through the Myasthenia Gravis Foundation of America.

Participant milestones

Measure	Privigen/Hizentra Privigen: 3 rounds of IV privigen was infused every 4 weeks until baseline visit week 0. Hizentra: Hizentra infused sub cutaneously based on weight and subject prescribed dose.
Overall Study STARTED	23
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Privigen/Hizentra Privigen: 3 rounds of IV privigen was infused every 4 weeks until baseline visit week 0. Hizentra: Hizentra infused sub cutaneously based on weight and subject prescribed dose.
Overall Study Did not pass screening phase	1

Baseline Characteristics

As per the protocol, only those patients who completed the screening phase are eligible for analysis. In our case this is 22 out of 23 patients.

Baseline characteristics by cohort

Measure	Hizentra n=23 Participants Hizentra is a subcutaneous (under the skin) immunoglobin (SCIg). Participants will receive weekly Hizentra. Dose and rate depend on the visit and how each participant tolerates the drug. Max flow rate not to exceed 100 mL per hour. HIZENTRA ®
Age, Categorical <=18 years	0 Participants n=23 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=23 Participants
Age, Categorical >=65 years	7 Participants n=23 Participants
Age, Continuous	51.36 years STANDARD_DEVIATION 17.001 • n=23 Participants
Sex: Female, Male Female	12 Participants n=23 Participants
Sex: Female, Male Male	11 Participants n=23 Participants
Race/Ethnicity, Customized Race · White	18 Participants n=23 Participants
Race/Ethnicity, Customized Race · African American	2 Participants n=23 Participants
Race/Ethnicity, Customized Race · Asian	1 Participants n=23 Participants
Race/Ethnicity, Customized Race · Other	1 Participants n=23 Participants
Race/Ethnicity, Customized Race · Unknown	1 Participants n=23 Participants
Region of Enrollment Canada	11 participants n=23 Participants
Region of Enrollment United States	12 participants n=23 Participants
Quantitative Myasthenia Gravis test at Baseline	10 points n=22 Participants • As per the protocol, only those patients who completed the screening phase are eligible for analysis. In our case this is 22 out of 23 patients.

PRIMARY outcome

Timeframe: Change from Baseline to Week 12

Population: 23 patients were enrolled in the study. The protocol mentions that only those subjects who have stable QMG in the screening phase will be considered eligible for analyses. In our case 22 out of 23 patients are eligible for the final analyses.

The QMG is a 13 item ordinal scale which measures ocular, bulbar, extremity fatigue and strength, along with respiratory function. The scale is from 0 - 3 for each item, with 0 meaning normal and 3 is severe. Total score can range from 0 to 39.

Change in MG severity will be measured using the Quantitative Myasthenia Gravis (QMG) Score for Disease severity. The QMG is a validated clinical composite scale. As mentioned in the protocol, our hypotheses are:

H0: Proportion of patients whose QMG scores are increased by more than 3 points at the end of the SCIg treatment phase ≤ 0.65 HA: Proportion of patients whose QMG scores are increased by no more than 3 points at the end of the SCIg treatment phase > 0.65

Thus, analysis of the primary outcome is done as a one-sample Z test of proportions. That is, the QMG is a continuous outcome, but analyses results are reported as proportions.

Outcome measures

Measure	Hizentra n=22 Participants Hizentra is a subcutaneous (under the skin) immunoglobin (SCIg). Participants will receive weekly Hizentra. Dose and rate depend on the visit and how each participant tolerates the drug. Max flow rate not to exceed 100 mL per hour. HIZENTRA ®
Proportion of Patients Whose Quantitative Myasthenia Gravis Scores Are Increased by no More Than 3 Points at the End of the SCIg Treatment Phase	0.864 proportion of participants Interval 0.72 to 1.0

SECONDARY outcome

Timeframe: Change from Baseline to Week 12

Population: Here we consider the 22 participants on whom the MG-ADL scores at either baseline or Week 12 are available for analysis.

Myasthenia Gravis-specific Activities of Daily Living scale (MG-ADL): Composite measure of scores from measurement scales. The MG-ADL has a scale of 0 - 24 with 0 being the lowest (no symptoms) and 24 being the highest (most severe symptoms. The MG-ADL is a staff-administered, patient-reported questionnaire that measures 8 commons symptoms of myasthenia gravis and grades them on a scale of 0 - 3.

Outcome measures

Measure	Hizentra n=22 Participants Hizentra is a subcutaneous (under the skin) immunoglobin (SCIg). Participants will receive weekly Hizentra. Dose and rate depend on the visit and how each participant tolerates the drug. Max flow rate not to exceed 100 mL per hour. HIZENTRA ®
Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL) Scores Week 12	3 score on a scale Interval 0.0 to 4.5
Myasthenia Gravis-specific Activities of Daily Living Scale (MG-ADL) Scores Baseline	3 score on a scale Interval 1.0 to 7.0

SECONDARY outcome

Timeframe: Change from Baseline to Week 12

Population: Here we consider the 22 participants on whom the MG-ADL scores at either baseline or Week 12 are available for analysis.

MG Quality of Life (QOL)-15: Composite measure of scores from measurement scales. The MG QOL-15 is a questionnaire answered by the patient that asked about different symptoms of MG. The questionnaire consists of 15 questions that are graded on a scale of 0 - 4. The total score has a range of 0 - 60 with a higher score meaning more severe symptoms or a worse outcome.

Outcome measures

Measure	Hizentra n=22 Participants Hizentra is a subcutaneous (under the skin) immunoglobin (SCIg). Participants will receive weekly Hizentra. Dose and rate depend on the visit and how each participant tolerates the drug. Max flow rate not to exceed 100 mL per hour. HIZENTRA ®
Myasthenia Gravis Quality of Life (MG QOL-15) Scores Week 12	16 score on a scale Interval 6.5 to 32.75
Myasthenia Gravis Quality of Life (MG QOL-15) Scores Baseline	22 score on a scale Interval 9.0 to 28.5

SECONDARY outcome

Timeframe: Change from Baseline to Week 12

Population: Here we consider the 21 participants on whom the MG-Composite scores are available for analysis.

The MGC takes scores from the MG-ADL, the QMG, and combines them will manual muscle testing scores to create the MGC. The scale of this score ranges from 0 - 50 with higher scores meaning a worse outcome or more sever symptoms.

Outcome measures

Measure	Hizentra n=21 Participants Hizentra is a subcutaneous (under the skin) immunoglobin (SCIg). Participants will receive weekly Hizentra. Dose and rate depend on the visit and how each participant tolerates the drug. Max flow rate not to exceed 100 mL per hour. HIZENTRA ®
Myasthenia Gravis Composite (MGC) Score Week 12	4 score on a scale Interval 0.25 to 10.75
Myasthenia Gravis Composite (MGC) Score Baseline	6 score on a scale Interval 1.0 to 12.0

SECONDARY outcome

Timeframe: Change from Baseline to Week 12

Population: This secondary outcome was recorded for 18 patients. Analysis is done as per the protocol.

Treatment Satisfaction Questionnaire for Medication (TSQM) - Convenience Score measured on a scale of 0 to 100. 0 indicates no treatment convenience satisfaction and 100 indicates highest treatment convenience satisfaction.

Outcome measures

Measure	Hizentra n=18 Participants Hizentra is a subcutaneous (under the skin) immunoglobin (SCIg). Participants will receive weekly Hizentra. Dose and rate depend on the visit and how each participant tolerates the drug. Max flow rate not to exceed 100 mL per hour. HIZENTRA ®
Treatment Satisfaction Questionnaire for Medication (TSQM) - Convenience Score Week 12	75 score on a scale Interval 47.2 to 81.9
Treatment Satisfaction Questionnaire for Medication (TSQM) - Convenience Score Baseline	69.40 score on a scale Interval 51.4 to 77.8

SECONDARY outcome

Timeframe: Change from Baseline to Week 12

Population: This secondary outcome was recorded for 20 patients. Analysis is done as per the protocol.

Treatment Satisfaction Questionnaire for Medication (TSQM) - Effectiveness Score measured on a scale of 0 to 100. 0 indicates no treatment effectiveness satisfaction and 100 indicates highest treatment effectiveness satisfaction.

Outcome measures

Measure	Hizentra n=20 Participants Hizentra is a subcutaneous (under the skin) immunoglobin (SCIg). Participants will receive weekly Hizentra. Dose and rate depend on the visit and how each participant tolerates the drug. Max flow rate not to exceed 100 mL per hour. HIZENTRA ®
Treatment Satisfaction Questionnaire for Medication (TSQM) - Effectiveness Score Week 12	79.20 score on a scale Interval 52.1 to 100.0
Treatment Satisfaction Questionnaire for Medication (TSQM) - Effectiveness Score Baseline	75 score on a scale Interval 50.0 to 83.3

SECONDARY outcome

Timeframe: Change from Baseline to Week 12

Population: This secondary outcome was recorded for 18 patients. Analysis is done as per the protocol.

Treatment Satisfaction Questionnaire for Medication (TSQM) - Satisfaction Score measured on a scale of 0 to 100. 0 indicates no treatment satisfaction and 100 indicates highest treatment satisfaction.

Outcome measures

Measure	Hizentra n=18 Participants Hizentra is a subcutaneous (under the skin) immunoglobin (SCIg). Participants will receive weekly Hizentra. Dose and rate depend on the visit and how each participant tolerates the drug. Max flow rate not to exceed 100 mL per hour. HIZENTRA ®
Treatment Satisfaction Questionnaire for Medication (TSQM) - Satisfaction Score Week 12	83.30 score on a scale Interval 45.8 to 91.7
Treatment Satisfaction Questionnaire for Medication (TSQM) - Satisfaction Score Baseline	75 score on a scale Interval 58.3 to 97.9

SECONDARY outcome

Timeframe: Change from "Week -10 to Week 0" versus "Week 1 to Week 12"

Population: Note: Change in IgG from Week -10 to Week 0 can be assessed for 20 participants. Change in IgG from Week 1 to Week 12 can be assessed for 19 participants.

Measure IgG level (mg/dL) between intravenous and subcutaneous study phases. Normal range equals 762-1488 mg/dL.

Outcome measures

Measure	Hizentra n=20 Participants Hizentra is a subcutaneous (under the skin) immunoglobin (SCIg). Participants will receive weekly Hizentra. Dose and rate depend on the visit and how each participant tolerates the drug. Max flow rate not to exceed 100 mL per hour. HIZENTRA ®
Immunoglobulin G (IgG) Antibody Levels Change: Week -10 to Week 0	661 mg/dL Interval 496.25 to 981.0
Immunoglobulin G (IgG) Antibody Levels Change: Week 1 to Week 12	-54 mg/dL Interval -423.0 to 150.0

SECONDARY outcome

Timeframe: 12 weeks from start of SCIg

Tolerability is assessed as the number of subjects who completed the study and/or did not withdraw due to worsening.

Outcome measures

Measure	Hizentra n=22 Participants Hizentra is a subcutaneous (under the skin) immunoglobin (SCIg). Participants will receive weekly Hizentra. Dose and rate depend on the visit and how each participant tolerates the drug. Max flow rate not to exceed 100 mL per hour. HIZENTRA ®
Tolerabililty	20 Participants

Adverse Events

Privigen/Hizentra

Serious events: 6 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Measure	Privigen/Hizentra n=23 participants at risk Experimental Treatment arm: Privigen/Hizentra assigned to subjects who are stable in the screening phase of the study.
Vascular disorders Thromboembolic event	4.3% 1/23 • Number of events 1 • 23 weeks
Musculoskeletal and connective tissue disorders Generalized muscle weakness	8.7% 2/23 • Number of events 2 • 23 weeks
Ear and labyrinth disorders Vertigo	4.3% 1/23 • Number of events 2 • 23 weeks
Nervous system disorders Seizure	4.3% 1/23 • Number of events 1 • 23 weeks
Psychiatric disorders Psychiatric Disorders- Other	4.3% 1/23 • Number of events 1 • 23 weeks

Other adverse events

Measure	Privigen/Hizentra n=23 participants at risk Experimental Treatment arm: Privigen/Hizentra assigned to subjects who are stable in the screening phase of the study.
Skin and subcutaneous tissue disorders Injection Site Reactions	13.0% 3/23 • Number of events 10 • 23 weeks
Musculoskeletal and connective tissue disorders Myalgia	8.7% 2/23 • Number of events 2 • 23 weeks
Gastrointestinal disorders Nausea	8.7% 2/23 • Number of events 3 • 23 weeks
Nervous system disorders Headache	13.0% 3/23 • Number of events 3 • 23 weeks
Cardiac disorders Palpitations	4.3% 1/23 • Number of events 1 • 23 weeks
Psychiatric disorders Insomnia	4.3% 1/23 • Number of events 1 • 23 weeks
Gastrointestinal disorders Dyspepsia	4.3% 1/23 • Number of events 1 • 23 weeks
Nervous system disorders Paresthesia	4.3% 1/23 • Number of events 1 • 23 weeks
Gastrointestinal disorders Gastroesophageal Reflux Disease	4.3% 1/23 • Number of events 1 • 23 weeks
Blood and lymphatic system disorders Blood and Lymphatic System Disorder	8.7% 2/23 • Number of events 3 • 23 weeks
Musculoskeletal and connective tissue disorders Back Pain	13.0% 3/23 • Number of events 3 • 23 weeks
Infections and infestations Upper Respiratory Infection	8.7% 2/23 • Number of events 2 • 23 weeks
Skin and subcutaneous tissue disorders Hyperhydrosis	4.3% 1/23 • Number of events 1 • 23 weeks
General disorders Fatigue	8.7% 2/23 • Number of events 2 • 23 weeks
General disorders Neck edema	4.3% 1/23 • Number of events 1 • 23 weeks
Injury, poisoning and procedural complications Bruising	8.7% 2/23 • Number of events 3 • 23 weeks
Musculoskeletal and connective tissue disorders Neck Pain	4.3% 1/23 • Number of events 1 • 23 weeks
Infections and infestations Bronchial Infection	4.3% 1/23 • Number of events 1 • 23 weeks
General disorders Edema Limbs	4.3% 1/23 • Number of events 4 • 23 weeks
Eye disorders Eye Disorders	4.3% 1/23 • Number of events 2 • 23 weeks
Gastrointestinal disorders Bloating	8.7% 2/23 • Number of events 2 • 23 weeks
Nervous system disorders Dizziness	8.7% 2/23 • Number of events 2 • 23 weeks
Musculoskeletal and connective tissue disorders Generalized Muscle Weakness	4.3% 1/23 • Number of events 1 • 23 weeks
Skin and subcutaneous tissue disorders Rash Acneiform	8.7% 2/23 • Number of events 2 • 23 weeks
Vascular disorders Hematoma	4.3% 1/23 • Number of events 1 • 23 weeks
Nervous system disorders Spasticity	4.3% 1/23 • Number of events 1 • 23 weeks
Musculoskeletal and connective tissue disorders Pain Extremity	4.3% 1/23 • Number of events 1 • 23 weeks
Eye disorders Blurred Vision	4.3% 1/23 • Number of events 1 • 23 weeks
Vascular disorders Hypertension	4.3% 1/23 • Number of events 1 • 23 weeks
Musculoskeletal and connective tissue disorders Musculoskeletal and Connective Tissue Disorder Other	4.3% 1/23 • Number of events 1 • 23 weeks
Respiratory, thoracic and mediastinal disorders Dyspnea	4.3% 1/23 • Number of events 1 • 23 weeks
Skin and subcutaneous tissue disorders Skin and subcutaneous tissue disorders	4.3% 1/23 • Number of events 1 • 23 weeks
General disorders Flu like symptoms	4.3% 1/23 • Number of events 1 • 23 weeks
Nervous system disorders Dysarthria	4.3% 1/23 • Number of events 1 • 23 weeks
General disorders Pain	4.3% 1/23 • Number of events 1 • 23 weeks
Renal and urinary disorders Increased Creatinine	4.3% 1/23 • Number of events 1 • 23 weeks

Additional Information

Dr. Mazen Dimachkie

University of Kansas Medical Center

Phone: 913-588-6970

Email: mdimachkie@kumc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place