A Study to Evaluate the Efficacy, Safety and PD and PK of HBM9161 in MG Patients

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Pharmacodynamic and Pharmacokinetic of HBM9161 (HL161) Subcutaneous Injection in Patients With Generalized Myasthenia Gravis

Primary Objectives: To investigate the efficacy of HBM9161 in patients with attack of MG in China

Study Overview

• Status: Completed
• Conditions: Myasthenia Gravis
• Intervention / Treatment: Drug: HBM9161 Injection (680mg and 340 mg); Drug: HBM9161 Injection (340 mg); Drug: Placebos

Detailed Description

This is a multicenter, randomized, double-blind and placebo-controlled study. The investigational drug is HBM9161 injection, and the indication is MG.

The subjects will be randomized to three dose groups (340mg, 680mg and placebo) for a 6 weeks' double-blind treatment period followed by an open-label extension treatment period. The study will investigate the safety, efficacy and pharmacodynamic and pharmacokinetic of HBM9161 in patients with attack of MG in China.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Huashan Hospital, Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed Informed Consent Form.
2. Male or female ≥ 18 years of age.

3. A female participant is eligible to participate if she is of:

   1. Non-childbearing potential (physically infertile, including women who have been menopausal for 2 years or more);
   2. Childbearing potential, negative serum pregnancy test results at screening visits, and agree to consistently use acceptable and effective contraceptive methods until 14 days after the final visit.
4. A male participant must take effective contraception during this clinical trial or their heterosexual partner must take effective contraception.

5. Positive serologic test for AChR-Ab or MUSK-Ab at the screening visit and at least 1 of the following:

   1. History of abnormal neuromuscular transmission test demonstrated by sign-fiber-electromyography or repetitive nerve stimulation OR
   2. History of positive edrophonium chloride test OR
   3. Participant has demonstrated improvement in MG signs on oral cholinesterase inhibitors as assessed by the treating physician.

Exclusion Criteria:

1. Use of rituximab, belimumab, eculizumab or any monoclonal antibody/Fc-fusion biologic for immunomodulation within 6 months prior to screening.
2. Immunoglobulins given by SC, IV(IVIG), or intramuscular route, or plasmapheresis/plasma exchange (PE) within 4 weeks before screening.
3. Thymectomy performed < 12 months prior to screening.
4. Total IgG level <6g/L (at screening).
5. Participant has any laboratory abnormality (at screening) that, in the opinion of the investigator, is clinically significant, has not resolved at baseline, and could jeopardize or would compromise the participant's ability to participate in this study.
6. Have known autoimmune disease other than MG that would interfere with the course and conduct of the study (such as uncontrolled thyroid disease).
7. Have an active infection, a recent serious infection (i.e., requiring injectable antimicrobial therapy or hospitalization) within the 8 weeks prior to screening.
8. History of or known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or Mycobacterium tuberculosis. Participants must have negative test results for HBV surface antigen, HBV core antibody, HCV antibody, HIV 1 and 2 antibodies and a negative TB test at screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HBM9161 (680mg and 340 mg); Subcutaneous injection; Blinded: HBM9161 680mg; Open-label: HBM9161 340mg;	Drug: HBM9161 Injection (680mg and 340 mg); HBM9161 Injection (680mg and 340mg)
Experimental: HBM9161 (340 mg); Subcutaneous injection; Blinded: HBM9161 340mg; Open-label: HBM9161 340mg;	Drug: HBM9161 Injection (340 mg); HBM9161 Injection (340 mg)
Placebo Comparator: Placebo, HBM9161 (340 mg); Subcutaneous injection; Blinded: Placebo; Open-label: HBM9161 340mg;	Drug: Placebos; Placebo, HBM9161 Injection (340mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score from baseline to Day 43	The MG-ADL profile provides an assessment of MG symptom severity and measures 8 items on a 0-3 scale, with 0 being the least severe. The total sum of the 13 items represents the ADL score. The ADL score can range from 0 (least severe) to 24 (most severe)	43 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Myasthenia Gravis Composite (MGC) score from baseline to Day 43	The total QMG score is obtained by summing the responses to each individual item (13 items; Responses: None=0, Mild=1, Moderate=2, Severe=3). The score ranges from 0 to 39, with lower scores indicating lower disease activity.	43 days
Change in the Quantitative Myasthenia Gravis (QMG) score from baseline to Day 43	The QMG test is a standardized quantitative strength scoring system and measures 13 items on a 0-3 scale, with 0 being the least severe. The total sum of the 13 items represents the QMG score. The QMG score can range from 0 (least severe) to 39 (most severe).	43 days
Change in the Myasthenia Gravis Quality of Life 15(MG-QoL15r) score from baseline to Day 43	The MG-QoL 15r scale is a patient-reported score that assesses the patient's perception of impairment and disability and the degree to which the patient tolerates disease manifestations. Each question was graded on a 3-point scale from 0=normal to 2=severe with a score of 0 to 30; the higher score indicates worse MG disease activity	43 days
Proportion of participants with a decrease on the MG-ADL Score by ≥ 2 points		43 days
Proportion of participants with an improvement and worse on the MGFA Post-intervention Status (MGFA-PIS) from baseline to Day 43.		43 days
Change in the MG-ADL score from baseline to Day 120	The MG-ADL profile provides an assessment of MG symptom severity and measures 8 items on a 0-3 scale, with 0 being the least severe. The total sum of the 13 items represents the ADL score. The ADL score can range from 0 (least severe) to 24 (most severe)	120 days
Change in the MGC score from baseline to Day 120	The total QMG score is obtained by summing the responses to each individual item (13 items; Responses: None=0, Mild=1, Moderate=2, Severe=3). The score ranges from 0 to 39, with lower scores indicating lower disease activity.	120 days
Change in the QMG score from baseline to Day 120	The QMG test is a standardized quantitative strength scoring system and measures 13 items on a 0-3 scale, with 0 being the least severe. The total sum of the 13 items represents the QMG score. The QMG score can range from 0 (least severe) to 39 (most severe).	120 days
Change in the MG-QoL15r score from baseline to Day 120	The MG-QoL 15r scale is a patient-reported score that assesses the patient's perception of impairment and disability and the degree to which the patient tolerates disease manifestations. Each question was graded on a 3-point scale from 0=normal to 2=severe with a score of 0 to 30; the higher score indicates worse MG disease activity	120 days
Proportion of participants with persistent improvement on the MGC score from baseline to Day 120	Improvement (decrease) in the MGC score by ≥ 3 points for 6 weeks	120 days
Proportion of participants with persistent improvement on the MG-ADL score from baseline to Day 120	Improvement (decrease) in the MG-ADL Score by ≥ 2 points for 6 weeks	120 days

Collaborators and Investigators

• Sponsor: Harbour BioMed (Guangzhou) Co. Ltd.
• Investigators: Principal Investigator: Chongbo Zhao, Huashan Hospital

Publications and helpful links

General Publications

• Yan C, Duan RS, Yang H, Li HF, Zou Z, Zhang H, Zhou H, Li XL, Zhou H, Jiao L, Chen J, Yin J, Du Q, Lee M, Chen Y, Chen X, Zhao C. Therapeutic Effects of Batoclimab in Chinese Patients with Generalized Myasthenia Gravis: A Double-Blinded, Randomized, Placebo-Controlled Phase II Study. Neurol Ther. 2022 Jun;11(2):815-834. doi: 10.1007/s40120-022-00345-9. Epub 2022 Apr 12.

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2020
• Primary Completion (Actual): August 24, 2021
• Study Completion (Actual): August 24, 2021

Study Registration Dates

• First Submitted: April 13, 2020
• First Submitted That Met QC Criteria: April 14, 2020
• First Posted (Actual): April 15, 2020

Study Record Updates

• Last Update Posted (Actual): September 8, 2021
• Last Update Submitted That Met QC Criteria: September 6, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: MG
• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neuromuscular Diseases; Neurodegenerative Diseases; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myasthenia Gravis
• Other Study ID Numbers: 9161.3

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No