Evaluate the Efficacy and Safety of HBM9161(HL161)Subcutaneous Injection in Patients With Generalized MG Patients (MG)

A Multicenter, Randomized, Double-blind, Placebo-controlled, Seamless and Group Sequential Phase 2/3 Study to Evaluate the Efficacy and Safety of HBM9161 (HL161) Subcutaneous Injection in Patients With Generalized Myasthenia Gravis

Primary study objective: To verify the efficacy of HBM9161 subcutaneous injection in Chinese patients with gMG

Study Overview

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

Detailed Description

This is a multicenter, randomized, double-blind, placebo-controlled, seamless and group sequential phase 2/3 study to evaluate the efficacy and safety of HBM9161 (HL161) subcutaneous injection in patients with generalized myasthenia gravis Phase 3 study design: A total of 120 subjects with positive AChR-Ab or MuSK-Ab and up to 24 subjects with negative AChR-Ab and MuSK-Ab are planned for this phase (The randomization will end after approximately 120 subjects with positive serum AchR-Ab or MUSK-Ab are enrolled) and randomized into 2 treatment regimens in a 1:1 ratio. Arm 1 will receive HBM9161 680 mg; Arm 2 will receive placebo. Whether or not AChR-Ab or MuSK-Ab is positive, and whether or not concomitant steroids are used will be randomization stratification factors.

First, eligible subjects will be screened into the double-blind treatment phase and blindly assigned to receive either HBM9161 680 mg or placebo for the first treatment period, administered once weekly (QW) for 6 doses.

Subjects who complete the first treatment period will start the administration of the second treatment period if they meet the dosing criteria for the second treatment period at Week 9.

The second treatment period will be administered once weekly (QW) for a total of 6 doses in the first treatment period, followed by an observation period (4 weeks) and a follow-up period. Subjects will be dosed for up to two treatment cycles during the study.

• 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 Contact Backup: Name: Jianying Xi; Phone Number: +86 13671669680; Email: xijianying@fudan.edu.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Huashan Hospital, Fudan University
      • Contact: Chongbo Zhao; Phone Number: +86 13701822316; Email: zhao_chongbo@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Signed written informed consent form (ICF).
2. Male or female ≥ 18 years of age at the screening visit.

3. Female subjects must meet the following conditions to participate in this study:

   1. Not of childbearing potential (ie, physiologically incapable of becoming pregnant, including women who have been postmenopausal for 2 or more years);

   2. Of potential childbearing potential, have a negative serum pregnancy test result at the screening visit, and agree to adhere to one of the following acceptable effective methods of contraception (ie, per approved product label insert and physician instructions) consistently and correctly during the study, from the screening visit onwards until 14 days after the final visit:

      • Total abstinence (based on subject preference and previous lifestyle); or
      • Implantation of a levonorgestrel implant at least 1 month prior to study drug administration, but no longer than 3 years; or
      • Injection of a progestogen at least 1 month prior to study drug administration; or
      • A cycle of oral contraceptives (combined contraceptives or progestin-only) for at least 1 month prior to study drug administration; or
      • Double contraception: condom or cervical cap (diaphragm or cervical cap) plus spermicide (foam/gel/cream/suppository); or
      • An intrauterine device, implanted by a qualified physician; or
      • Estrogen vaginal ring; or
      • Contraceptive patch.
4. Male subjects must use effective contraceptive methods or have their heterosexual partners use effective contraceptive methods during their participation in this clinical trial.
5. Meets MGFA myasthenia gravis clinical classification IIa-IVa (includes types IIa, IIb, IIIa, IIIb, and IVa) at the screening visit and at the baseline visit.

6. Positive or negative AchR-Ab/MUSK-Ab at the screening visit and meets at least 1 of the following 3 criteria:

   1. Repeated electrical stimulation indicates neuromuscular junction transmission disorder (including medical history record);
   2. Positive Tensilon test or neostigmine test (including medical history record);
   3. The patient's MG symptoms improve after treatment with oral cholinesterase inhibitors at the judge of the physician.
7. Results from clinical laboratory tests at screening must be acceptable to the investigator.

Exclusion Criteria:

1. Has a serious illness or condition other than myasthenia gravis that, in the judgment of the investigator, would put the subject at risk because of participation in the study, or that would affect the results of the study and the subject's ability to participate in the 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. Subjects with severe myasthenia gravis (such as Type IVb or V) who are judged by the investigator to be inappropriate for this study (e.g., expected to require artificial assisted ventilation during the study).
4. Presence of 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.
5. Has received a vaccine injection (including the COVID-19 vaccine) 4 weeks prior to the Screening Visit or is scheduled to receive a vaccine injection during the study.
6. Any active infection at the Screening Visit or serious infection requiring treatment with intravenous anti-infective drugs or hospitalization within 8 weeks before the Screening Visit.
7. Current or past 1 year alcohol or drug dependence/abuse, except nicotine and coffee.
8. Subjects who are allergic to the trial drug or its components; or history of clinically significant allergic disease (including drug allergies, anaphylaxis) that, in the opinion of the investigator, affects the subject's participation in this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Experimental: HBM9161 (680mg ); HBM9161 680mg; First treatment period: Subcutaneous injection, QW for 6 doses; Second treatment period: Subcutaneous injection, QW for 6 doses	Drug: HBM9161 Injection (680mg); HBM9161 Injection
Placebo Comparator: Placebo Comparator: Placebo; Placebo; First treatment period: Subcutaneous injection, QW for 6 doses; Second treatment period: Subcutaneous injection, QW for 6 doses	Drug: Placebos; Placebo Injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with sustained improvement (AChR-Ab-positive or MuSK-Ab-positive patient population) during the first treatment period and observation period	a reduction of ≥ 3 points from the baseline of Myasthenia Gravis Activities of Daily Living Scale (MG-ADL) score that persists for at least 64 days	baseline to Day 64

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with sustained improvement (i.e. Entire Population) during the first treatment period and observation period	a reduction of ≥ 3-point from the baseline of Myasthenia Gravis Activities of Daily Living Scale (MG-ADL) score that persists for at least 64 days	Baseline to Day 64
Percentage of patients with sustained improvement (AChR-Ab-positive or MuSK-Ab-positive patient population) during the first treatment period and observation period	a reduction of ≥ 3 points from the baseline of Quantitative Myasthenia Gravis (QMG) score that persists for at least 64 days	Baseline to Day 64
Percentage of patients with sustained improvement (AChR-Ab-positive or MuSK-Ab-positive patient populations) during the second treatment period and observation period	a reduction of ≥ 3 points from the baseline of MG-ADL score that persisted for at least 64 days	Baseline to Day 64

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2021
• Primary Completion (Anticipated): March 30, 2023
• Study Completion (Anticipated): October 30, 2023

Study Registration Dates

• First Submitted: August 29, 2021
• First Submitted That Met QC Criteria: September 1, 2021
• First Posted (Actual): September 9, 2021

Study Record Updates

• Last Update Posted (Actual): January 6, 2022
• Last Update Submitted That Met QC Criteria: December 15, 2021
• Last Verified: December 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 ph3

Drug and device information, study documents

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