Clinical trial NCT04346888: A Study to Evaluate the Efficacy, Safety and PD and PK of HBM9161 in MG Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myasthenia Gravis
Keywords: MG
Lead sponsor: Harbour BioMed (Guangzhou) Co. Ltd.
Sponsor class: INDUSTRY
First posted: 2020-04-15
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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. 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. Screening and baseline MG-ADL score ≥ 6, and \< 50% of them is from ocular muscle.
7. Stable background MG treatments at randomization.
8. 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.

Primary outcomes:
measure: Change in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score from baseline to Day 43
timeFrame: 43 days
Secondary outcomes:
measure: Change in the Myasthenia Gravis Composite (MGC) score from baseline to Day 43
timeFrame: 43 days
measure: Change in the Quantitative Myasthenia Gravis (QMG) score from baseline to Day 43
timeFrame: 43 days
measure: Change in the Myasthenia Gravis Quality of Life 15(MG-QoL15r) score from baseline to Day 43
timeFrame: 43 days
measure: Proportion of participants with a decrease on the MG-ADL Score by ≥ 2 points from baseline to Day 43
timeFrame: 43 days
measure: Proportion of participants with an improvement and worse on the MGFA Post-intervention Status (MGFA-PIS) from baseline to Day 43. o Improvement: MGC Score reduce ≥ 3 points o Aggravation: MGC Score increase ≥ 3 points
timeFrame: 43 days
measure: Change in the MG-ADL score from baseline to Day 120
timeFrame: 120 days
measure: Change in the MGC score from baseline to Day 120
timeFrame: 120 days
measure: Change in the QMG score from baseline to Day 120
timeFrame: 120 days
measure: Change in the MG-QoL15r score from baseline to Day 120
timeFrame: 120 days
measure: Proportion of participants with persistent improvement on the MGC score from baseline to Day 120
timeFrame: 120 days
measure: Proportion of participants with persistent improvement on the MG-ADL score from baseline to Day 120
timeFrame: 120 days
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
state: Shanghai
Study officials:
affiliation: Huashan Hospital
name: Chongbo Zhao
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.