Evaluate the Safety of HBM9161 (HL161) Subcutaneous Injection in Patients With Generalized Myasthenia Gravis

A Long-term Open-label Extension Study to Evaluate the Safety of HBM9161 (HL161) Subcutaneous Injection in Patients With Generalized Myasthenia Gravis

The primary study objective is to evaluate medium- and long-term safety of HBM9161 in combination with background treatment for gMG patients through the observation on adverse events and laboratory abnormalities during study period.

Study Overview

• Status: Not yet recruiting
• Conditions: Myasthenia Gravis
• Intervention / Treatment: Drug: HBM9161 Injection (680mg); Drug: HBM9161 Drug Product (340mg)

• Study Type: Interventional
• Enrollment (Anticipated): 144
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chongbo Zhao; Phone Number: +86 13701822316; Email: zhao_chongbo@fudan.edu.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Huashan Hospital, Fudan University
      • Contact: Chongbo Zhao; Phone Number: +8613701822316; Email: zhao_chongbo@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- 1. Patients who have completed the HBM9161.3 Phase 3 study. 2. Signed written informed consent. 3. Suitable for continued treatment with study drug as judged by the investigator.

4. A total MG-ADL score of ≥ 5 or a reduction of MG-ADL score ≤ 3 points from the baseline of 9161.3 Phase 3 study.

5. Allow to use nonhormonal immunosuppressants or cholinesterase inhibitors (see "Concomitant Medications and Therapies" for definition) at a stable dose and route of administration since the administration of study drug in the 9161.3 Phase 3 study. Oral corticosteroids (≤ 40 mg/day prednisone or equivalent) are allowed but at a stable dose. Stable therapy is defined as follows:

1. Cholinesterase inhibitors: The dose is stable for more than 4 weeks during the visits; and the administration should be suspended for more than 12 hours during all clinical assessments;
2. Corticosteroids: initiated at least 3 months prior to the randomization visit and administration as a stable dose (the total daily dose of glucocorticoids should not exceed 40 mg of prednisone or equivalent) for at least 1 month at the randomization visit;

3. Immunosuppressants:

   Azathioprine: initiated at least 12 months prior to the randomization visit and a stable dose for at least 4 months at the randomization visit.

   Other immunosuppressive drugs (e.g., cyclophosphamide, cyclosporine A, tacrolimus, mofetil, methotrexate, etc.): initiated at least 6 months prior to the randomization visit and a stable dose for at least 3 months at the randomization visit.

   6. Female patients of childbearing potential and male patients with female partners of childbearing potential can participate in this study, but reliable contraceptive measures must be taken (such as physical barrier contraception (patients and their partners), contraceptive pills or patches, spermicide and barrier or intrauterine device). Up to 60 days after the last dose.

   7. A negative urine pregnancy at baseline must be observed for women of childbearing age.

   Exclusion Criteria:

   • 1. Had received any other clinical study drug since the administration of the study drug in the 9161.3 Phase 3 study.

     2. Females who are pregnant or lactating or planning to become pregnant during the study period, or females of childbearing potential who are not using an effective method of contraception.

     3. Patients with severe myasthenia gravis (such as Type IVb or V), which are judged by the investigator to be not suitable for this study (e.g., artificial assisted ventilation may be required during the study period).

     4. Subjects who received intravenous gamma globulin or plasma exchange treatment, with the last completed dose less than 4 weeks prior to the Screening Visit.

     5. Patients with other autoimmune diseases (such as uncontrolled thyroid disease, severe rheumatoid arthritis, etc.) that may affect the efficacy assessment of the study drug or affect participation in this study.

     6. Patients with other concurrent diseases or conditions that may affect the efficacy assessment of the study drug for the treatment of myasthenia gravis.

     7. Patients who received a vaccine injection 4 weeks prior to the Screening Visit or are scheduled to receive a vaccine injection during the study (including the COVID-19 vaccine).

     8. Patients with any active infection at the Screening Visit or serious infection (requiring intravenous anti-infective treatment or hospitalization) within 8 weeks before the screening visit.

     9. Subjects with previous or current human immunodeficiency virus (HIV), hepatitis C virus (HCV) infection; subject has a positive test for any of the following at the Screening Visit: HCV antibody, HIV antibody type 1 and HIV antibody type 2.

     10. 9161.3 Phase 3 screening visit: a) Subjects who are positive for HBV surface antigen and have been receiving standard antiviral therapy (recommended to use Entecavir) for at least 2 weeks prior to the first dose of study drug (as confirmed by medical documents), but do not continue antiviral therapy during the commitment study period until 6 months after discontinuation; b) Subjects who are negative for HBV surface antigen and positive for anti-HBV core antibody, with quantitative detection of HBV-DNA > 2000 IU/mL (the results of 9161.3 Phase 3 Exit Visit can be used for the above tests).

     11. Patients with previous or current infection with Mycobacterium tuberculosis (positive or indeterminate interferon gamma release test at 12 months prior to the screening visit).

     12. Patients with acute liver injury (e.g., hepatitis) or significant cirrhosis (Child-Pugh Class C) or any of the following (results from the 9161.3 phase 3 Exit Visit could have been used):

     1. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 2 times the upper limit of normal (ULN) at the Screening Visit according to the laboratory reference ranges.

     2. Total bilirubin > 1.5 times the upper limit of normal (ULN) at the screening visit according to the laboratory reference ranges.

        13. Clinically significant laboratory abnormality, in the opinion of the investigator, would pose a risk to the subject's participation in the study or interfere with study participation; or any of the following (the following items can be retested once during the screening period):

     1. Total serum IgG ≤ 6 g/L at the Screening Visit.
     2. Serum albumin < 3.0 g/dL at the Screening Visit.
     3. Blood neutrophils < 1.5 × 109/L at the Screening Visit.
     4. Blood calcium (or corrected calcium) exceed 5% of the normal range at the screening visit.

     5. Serum LDL-C ≥ 4.9 mmol/L at the Screening Visit; subjects which are treated with lipid-lowering drugs may be enrolled prior to starting study medication (Ezetimibe is recommended for lipid-lowering drugs).

        14. Subjects with significant cardiovascular, hepatic, renal, respiratory, endocrine, or hematologic disease, or other medical or psychiatric condition that the investigator considers to be an impediment for participating in the study or that may result in hospitalization during the study.

        15. Subjects with malignancy at any time, including bone marrow or lymphodysplastic disease, etc.

        16. Contraindicated drugs: Subjects who, in the investigator's judgment, are required to take prohibited drugs defined in the protocol during the screening and treatment period of this study.

        17. An investigator/site employee who is directly related to the study or is an immediate family member of an investigator/site employee who is directly related to the study ("immediate family member" is defined as a spouse, parent, child, or sibling, whether biological or legal).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HBM9161 Drug Product (680mg); HBM9161 680mg: subcutaneous injection, 6 times in total per treatment cycle, once a week; the second cycle of treatment should be launched 4 weeks after the last dose in the previous treatment cycle; if the disease state is still stable 4 weeks after the last dose, the observation can be continued until the disease activity is aggravated (improvement of MG-ADL < 3 points compared with the previous treatment cycle), and the next treatment cycle and the observation period can be started.	Drug: HBM9161 Injection (680mg); HBM9161 Injection
Experimental: HBM9161 Drug Product (340mg)(Enter low dose if required due to investigator assessment); HBM9161 340 mg: subcutaneous injection, 6 times in total per treatment cycle, once a week; the second cycle of treatment should be launched 4 weeks after the last dose in the previous treatment cycle; if the disease state is still stable 4 weeks after the last dose, the observation can be continued until the disease activity is aggravated (improvement of MG-ADL < 3 points compared with the previous treatment cycle), and the next treatment cycle and the observation period can be started.	Drug: HBM9161 Drug Product (340mg); HBM9161 Drug Product (340mg)(Enter low dose if required due to investigator assessment)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of AEs during the study	Incidence of AEs	during the study，up to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with sustained improvement (AChR-Ab-positive or MuSK-Ab-positive patient population)	reduction of MG-ADL score ≥ 3 points from the baseline for at least 4 weeks	during the first treatment cycle + observation period (baseline to Day 64)
Proportion of duration patients remained in clinical improvement	percentage of time patients achieving clinical improvement (reduction of MG-ADL score from baseline ≥ 3 points) at 26 Weeks from baseline through Week 24 (AChR-Ab Positive or MuSK-Ab Positive Patient Populations)	during the study，up to 24 weeks
Proportion of duration patients remained in clinical improvement	from baseline to Week 24, percentage of time patients remaining in clinical improvement (reduction of MG-ADL score from baseline ≥ 3 points) for 26 Weeks (Full Population)	during the study，up to 24 weeks
Proportion of duration patients remained in Minimal Symptom Expression	from baseline to Week 24, percentage of time patients remained in Minimal Symptom Expression (MSE, i.e., MG-ADL score of 0 or 1) for 24 Weeks (AChR-Ab-positive or MuSK-Ab-positive patient population)	during the study，up to 24 weeks
Improvement of patients' quality of life	Improvement of patients' quality of life	during the study，up to 24 weeks
Incidence and duration of serum anti-HBM9161 antibodies and neutralizing antibodies	Incidence and duration of serum anti-HBM9161 antibodies and neutralizing antibodies	during the study，up to 24 weeks

Collaborators and Investigators

• Sponsor: Harbour BioMed (Guangzhou) Co. Ltd.

Study record dates

Study Major Dates

• Study Start (Anticipated): April 30, 2022
• Primary Completion (Anticipated): May 30, 2023
• Study Completion (Anticipated): December 30, 2023

Study Registration Dates

• First Submitted: April 6, 2022
• First Submitted That Met QC Criteria: April 12, 2022
• First Posted (Actual): April 18, 2022

Study Record Updates

• Last Update Posted (Actual): April 18, 2022
• Last Update Submitted That Met QC Criteria: April 12, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Neoplasms by Site; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Neuromuscular Manifestations; Nervous System Neoplasms; Paraneoplastic Syndromes, Nervous System; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Muscle Weakness; Myasthenia Gravis
• Other Study ID Numbers: 9161.7

Drug and device information, study documents

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