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Trial record 1 of 1 for:    HBM9161 | neuromyelitis optica spectrum disorder
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A Study of HBM9161 in NMOSD Patients

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ClinicalTrials.gov Identifier: NCT04227470
Recruitment Status : Recruiting
First Posted : January 13, 2020
Last Update Posted : May 18, 2020
Sponsor:
Information provided by (Responsible Party):
Harbour BioMed (Guangzhou) Co. Ltd.

Brief Summary:
Primary Objectives:To investigate the safety and tolerability of HBM 9161 in patients with attack of NMOSD in China

Condition or disease Intervention/treatment Phase
NMO Spectrum Disorder Drug: HBM9161 Injection Phase 1

Detailed Description:

This is an open-label, dose exploration study.The investigational drug is HBM9161 injection, and the indication is NMOSD.

HBM9161(HL161BKN) is a human monoclonal antibody. HBM9161 targets the neonatal Fc receptor (FcRn) . By blocking the FcRn IgG-Fc binding site and accelerating the degradation of IgG, it can significantly reduce the total IgG level in blood (including pathological IgG).The serum aquaporin 4 antibody (AQP4-IgG) associated with NMOSD is a pathological IgG, so the combination of standard of care which is intravenous methylprednisolone (ivMP) with HBM9161 is expected to rapidly reduce AQP4-IgG levels.

Two dose groups (340 mg and 680 mg) were planned, and each dose group plans to enroll approximately 6 subjects. All subjects are weekly administered the HBM9161 by subcutaneous injection for a period of 4 weeks, together with standard of care which is of intravenous methylprednisolone (ivMP) by subcutaneous for a period of 4 weeks. The study will investigate the safety, and tolerability, pharmacodynamics and efficacy of HBM 9161 in patients with attack of NMOSD in China.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose exploration study.Two dose groups (340 mg and 680 mg) were planned, and each dose group plans to enroll approximately 6 subjects. Each subject will only participate in one dose group. Escalation to the next dose level decided by PIs and sponsor after evaluating safety data and PD data for lower dose group.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety, Tolerability, Pharmacodynamics and Efficacy of HBM9161 Weekly Subcutaneous Administration in Patients With Neuromyelitis Optica Spectrum Disorders (NMOSD) in China
Actual Study Start Date : March 31, 2020
Estimated Primary Completion Date : April 30, 2021
Estimated Study Completion Date : December 31, 2021


Arm Intervention/treatment
Experimental: Experimental: HBM9161, 340mg
HBM 9161 injection, 340mg, weekly administered by subcutaneous for a period of 4 weeks.
Drug: HBM9161 Injection
Subcutaneous injection; Weekly administered for a period of 4 weeks. All subjects are treated with the testing drug, add on intravenous methylprednisolone (ivMP) with gradually reduce the dose then to oral prednisone. After the administration of the testing drug, if the subject's symptoms get worsen, a rescue therapy need to be adopted as based on Investigator's judgement, the testing drug injection should be discontinued.

Experimental: Experimental: HBM9161, 680mg
HBM 9161 injection, 680mg, weekly administered by subcutaneous for a period of 4 weeks.
Drug: HBM9161 Injection
Subcutaneous injection; Weekly administered for a period of 4 weeks. All subjects are treated with the testing drug, add on intravenous methylprednisolone (ivMP) with gradually reduce the dose then to oral prednisone. After the administration of the testing drug, if the subject's symptoms get worsen, a rescue therapy need to be adopted as based on Investigator's judgement, the testing drug injection should be discontinued.




Primary Outcome Measures :
  1. Number of treatment related adverse events (AEs) [ Time Frame: 189 days ]
    Number of treatment related adverse events (AEs)


Secondary Outcome Measures :
  1. Immunoglobins changes from baseline to week 27 [ Time Frame: 189 days ]
    Change of concentration of immunoglobins in mg/ml overtime after administration of HBM9161 from baseline to week 27

  2. Neurological Disability changes from baseline to week 27 [ Time Frame: 189 days ]
    Neurological Disability changes from baseline to week 27 as measured by Expanded Disability Scale Score (EDSS, Score 0-10, higher means a worse outcome)

  3. Low Contrast Visual Acuity (LCVA) changes from baseline to week 27 [ Time Frame: 189 days ]
    Low Contrast Visual Acuity (LCVA) changes from baseline to week 27 as measured by Sloan Low Contrast Letter Scale (SLCLS Letter, Score 0-70, higher means a better outcome)

  4. Patient reported improvement changes from baseline to week 27 [ Time Frame: 189 days ]
    Patient reported improvement changes from baseline to week 27 as measured by Patient Global Impression-Improvement (PGI-I, Score 1-7, higher means a worse outcome)

  5. Percentage of patients who received rescue therapy [ Time Frame: 189 days ]
    Percentage of patients who received rescue therapy

  6. Percentage of patients who have relapse [ Time Frame: 189 days ]
    Percentage of patients who have relapse

  7. Walking ability changes from baseline to week 27 [ Time Frame: 189 days ]
    Walking ability changes from baseline to week 27 as measured by time used for 25-foot Walk (applicable for patients who are able to walk)

  8. The seropositive rate of anti-HBM9161 antibody after treatment [ Time Frame: 189 days ]
    Evaluation of the seropositive rate of anti-HBM9161 antibody after treatment


Other Outcome Measures:
  1. Maximum change from baseline to week 27 in total serum AQP4-IgG concentrations [ Time Frame: 189 days ]
    Maximum change from baseline in total serum AQP4-IgG concentrations

  2. AQP4-IgG changes from baseline to week 27 [ Time Frame: 189 days ]
    Change of serum concentration of AQP4-IgG overtime after administration of HBM9161 from baseline to week 27

  3. HBsAb level changes from baseline to week 27 [ Time Frame: 189 days ]
    Change in HBsAb level overtime after administration of HBM9161 from baseline to week 27



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. In visit 1, Male or female aged ≥ 18 years.
  2. Patient with NMOSD as defined by 2015 NMOSD diagnostic criteria by IPND (International Panel for NMO Diagnosis).
  3. Core clinical manifestations characterized by new acute optic neuritis and/or transverse myelitis. A clinical event is defined as an episode of inflammation in the spinal cord and/or optic nerve leading to neurologic deficits which can be identified by physical examination and not attributable to another disease process.
  4. The EDSS score of patients should be ≥ 3.5 and ≤7.5 at visit 1.
  5. AQP4-IgG is positive at visit 1 or had AQP4-IgG positive medical records before visit 1.
  6. Be able to recognize English letters.
  7. Patients should be on stable treatment of the following medications before visit 1(if anyone had a stable treatment ):

    • Immunosuppressant or immunomodulatory drugs

      • Azathioprine must be initiated at least 12 months ago and remain stable dosage for at least 4 months before screening.
      • Others (for example, cyclophosphamide, cyclosporin A, tacrolimus, mycophenolate mofetil and methotrexate) must be initiated at least 6 months ago and remain stable dosage for at least 3 months before screening.
    • Corticosteroids

      • At screening, the treatment dose must be stable for at least 1 month.
    • If patients received plasmapheresis or IVIg treatment, the last treatment dose/procedure must be finished at least 4 weeks ago before screening.

Exclusion Criteria:

  1. No acute optic neuritis and/or transverse myelitis symptoms or signs.
  2. Severe NMOSD which may require plasmapheresis or intravenous immunoglobulin (IVIG) treatment, in opinion of investigator, very soon.
  3. Have received plasmapheresis or IVIG treatment, the last treatment dose/procedure is less than 4 weeks before visit 1.
  4. Have known autoimmune diseases other than NMOSD that would interfere with efficacy assessment or participation in this study (such as uncontrolled thyroid disease or severe rheumatoid arthritis), or have any comorbid diseases which would interfere with the efficacy evaluation of HBM9161 on NMOSD.
  5. Have received rituximab or other anti-CD20 drugs treatment within 6 months before visit 1.
  6. Have been used any monoclonal antibodies or research drugs for immunomodulatory effects within 3 months before visit 1 or within 5 half-life periods of the drug.
  7. Females who are pregnant or lactating.
  8. Patients who can't tolerate or have contraindication to high dose intravenous methylprednisolone per Investigator's opinion.
  9. Have an active infection at visit 1, or a recent serious infection (i.e., requiring intravenous antimicrobial therapy or hospitalization) within 8 weeks before visit 1; or history of or existing infection of human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or Mycobacterium tuberculosis. Patients must have negative test results for HBV surface antigen, HBV core antibody, HCV antibody, HIV 1 and 2 antibodies, and a mycobacterium tuberculosis test (test method to be determined) at visit 1.
  10. Serum total IgG <700mg/dL at visit 1.
  11. Absolute neutrophil count <1500个/mm3 at visit 1 and/or visit 2
  12. Patients with acute liver function impairment (e.g., hepatitis) or severe liver cirrhosis (Child-Pugh Score, Class C)
  13. Any malignant tumor.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04227470


Contacts
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Contact: Wei Qiu +8620 8525 2327 qiuwei120@vip.163.com
Contact: Ting Shen +8620 8525 2327 646931073@qq.com

Locations
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China, Guangdong
Nanfang Hospital Recruiting
Guangzhou, Guangdong, China
Contact: Jinyu Chen    86-15876578154    568344684@qq.com   
Sponsors and Collaborators
Harbour BioMed (Guangzhou) Co. Ltd.
Investigators
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Principal Investigator: Wei Qiu Third Affiliated Hospital, Sun Yat-Sen University
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Responsible Party: Harbour BioMed (Guangzhou) Co. Ltd.
ClinicalTrials.gov Identifier: NCT04227470    
Other Study ID Numbers: 9161.2
First Posted: January 13, 2020    Key Record Dates
Last Update Posted: May 18, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Harbour BioMed (Guangzhou) Co. Ltd.:
NMOSD
Additional relevant MeSH terms:
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Neuromyelitis Optica
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Optic Nerve Diseases
Cranial Nerve Diseases
Demyelinating Diseases
Eye Diseases
Autoimmune Diseases
Immune System Diseases
Myelitis, Transverse
Optic Neuritis