search
Back to results

Study of NM8074 in Soliris-Treated Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

Primary Purpose

PNH - Paroxysmal Nocturnal Hemoglobinuria

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
NM8074
Sponsored by
NovelMed Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for PNH - Paroxysmal Nocturnal Hemoglobinuria

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Male or female patients ≥ 18 years at the time of consent Confirmation of PNH diagnosis by flow cytometry evaluation of red blood cells (RBCs) and white blood cells (WBCs), with granulocyte or monocyte clone size of ~5% Presence of one or more of the following PNH-related signs or symptoms within 3 months of Screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia: hemoglobin < 10 g/dL, history of a major adverse vascular event (including thrombosis), dysphagia, erectile dysfunction, PNH-mediated pRBC transfusions PNH patients must be undergoing treatment with Soliris for at least 3 months prior to screening, and must have a lactate dehydrogenase (LDH) level ≥ 1.5 times the upper limit of normal (ULN) during Screening Willing and able to understand and complete informed consent procedures, including signing and dating the informed consent form (ICF), and comply with the study visit schedule. Female subjects of childbearing potential must have a negative pregnancy test at Screening, and must not be planning pregnancy throughout the extent of the study term Female subjects of child-bearing potential and all male subjects must agree to use of effective contraception during study Soliris treated individuals must be able to provide documentation of vaccination against meningococcal infections. Exclusion Criteria: Platelet count < 30,000/µL at Screening Absolute neutrophil count (ANC) < 500 cells/µL at Screening Body weight < 85 lbs. (38 kg) at Screening Estimated glomerular filtration rate of < 30 mL/min/1.73m2 based on modification of diet in renal disease (MDRD) equation, creatinine clearance, or CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) at Screening Elevation of liver function tests: alanine aminotransferase (ALT) > 2xULN or direct bilirubin and alkaline phosphatase (ALP) both > 2xULN Has a known history of meningococcal disease or N. meningitidis infection Has an immunological disorder, such as, but not limited to, human immunodeficiency virus (HIV) infection (as evident by HIV-1 or HIV-2 antibody titer) or any acute or chronic infection including, but not limited to, hepatitis B virus (HBV) or hepatitis C virus (HCV) Currently active systemic infection or suspicion of active bacterial, viral, or fungal infection that requires antibiotic, antifungal, antiparasitic, or antiviral mediations Temperature > 38°C for more than two weeks prior to screening History of bone marrow or solid organ transplantation Pregnant, planning to become pregnant, or nursing female subjects Recent surgery requiring general anesthesia within the 2 weeks prior to Screening, or expected to have surgery requiring general anesthesia during the 12-week treatment period Active malignancy requiring surgery, chemotherapy, or radiation within the prior 12- months (subjects with a history of malignancy who have undergone curative resection or otherwise not requiring treatment for at least 12-months prior to screening with no detectable recurrences are allowed) History of any significant major medical conditions (cardiac, pulmonary, renal, e endocrine, or hepatic), or psychiatric disorder that, in the opinion of the Investigator, would make the subject unsuitable for participation in the study PNH patients currently under complement blocker treatments other than Soliris Concomitant use of anticoagulants is prohibited, if not on a stable regimen for at least 2 weeks prior to Day 1 Participation in any experimental small molecule or non-antibody therapy within 60 days prior to dosing on Day 1 (participation in observational studies and/or registry studies is permitted) Known or suspected history of illegal recreational drug or alcohol abuse within 1 year prior to start of screening Hypersensitivity or history of allergy to excipients in NM8074 formulation Unable or unwilling to comply with the requirements of the study

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    NM8074

    Arm Description

    All subjects will receive a dose of 15 mg/kg NM8074 every two weeks with a total of 6 doses, from Day 1 to Day 84 during the treatment period.

    Outcomes

    Primary Outcome Measures

    Normalization of serum LDH(Lactate dehydrogenase) levels from baseline levels
    Change from Baseline or Percent Change from Baseline in total hemoglobin levels (g/dL)
    Change from Baseline or Percent Change from Baseline in total number of units of packed red blood cells (pRBCs) transfused through Week 12
    Change from Baseline or Percent Change from Baseline in number of transfusions
    Percent Change from Baseline in Levels of Membrane Attack Complex (MAC) via Alternative Pathway (AP) of Complement Activity as Compared to Percent Change from Baseline in Levels of MAC via Classical Pathway (CP) of Complement Activity

    Secondary Outcome Measures

    Normalization of anemia
    Change from Baseline or Percent Change from Baseline in Reticulocyte Count
    Normalization of anemia
    Change from Baseline or Percent Change from Baseline in Bilirubin Levels
    Change from Baseline or Percent Change from Baseline of C3b deposition on PNH Type II and Type III RBCs via Flow Cytometry

    Full Information

    First Posted
    February 1, 2023
    Last Updated
    February 13, 2023
    Sponsor
    NovelMed Therapeutics
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT05731050
    Brief Title
    Study of NM8074 in Soliris-Treated Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
    Official Title
    A Phase II, Open Label, Multi Dose Study of NM8074 in Soliris-Treated Subjects With Paroxysmal Nocturnal Hemoglobinuria (PNH)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    June 2025 (Anticipated)
    Primary Completion Date
    August 2026 (Anticipated)
    Study Completion Date
    October 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    NovelMed Therapeutics

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The proposed study, NM8074-PNH-101, is a phase II, open-label, multi-dose, unicenter trial to evaluate the safety and efficacy of NM8074 in Soliris-treated PNH subjects.
    Detailed Description
    The proposed study, NM8074-PNH-101, will evaluate the safety and efficacy of NM8074 in Soliris-treated PNH subjects. The drug will be administered by intravenous (IV) infusion to adult patients who qualify based on the inclusion/exclusion criteria. A total of at least 6 patients (maximum of 10) with documented PNH and at least 3 months of Soliris treatment prior to Screening will be enrolled at the study site. The total duration of study term participation for all subjects will be up to 22 weeks, including a screening period of up to 8 weeks, a 12-week treatment period, and 2 weeks of a washout period. All subjects will receive a dose of 15 mg/kg NM8074 every two weeks with a total of 6 doses, from Day 1 to Day 84 during the treatment period.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    PNH - Paroxysmal Nocturnal Hemoglobinuria

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Sequential Assignment
    Model Description
    A total of at least 6 patients (maximum of 10) with documented PNH and at least 3 months of Soliris treatment prior to Screening will be enrolled at the study site. The total duration of study term participation for all subjects will be up to 22 weeks, including a screening period of up to 8 weeks, a 12-week treatment period, and 2 weeks of a washout period. All subjects will receive a dose of 15 mg/kg NM8074 every two weeks with a total of 6 doses, from Day 1 to Day 84 during the treatment period. No more than two subjects will be dosed in a single day.
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    6 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    NM8074
    Arm Type
    Experimental
    Arm Description
    All subjects will receive a dose of 15 mg/kg NM8074 every two weeks with a total of 6 doses, from Day 1 to Day 84 during the treatment period.
    Intervention Type
    Drug
    Intervention Name(s)
    NM8074
    Intervention Description
    NM8074 will be administered as an intravenous infusion. All enrolled subjects will receive a dose of 15 mg/kg NM8074 once every two weeks for a total of 6 doses from Day1 to Day 84. For Soliris-treated PNH subjects, admission and dosing of NM8074 on Day 1 should be scheduled to coincide with the next scheduled dose of Soliris (i.e., 14 ± 2 days after the last Soliris dose). Soliris should NOT be administered on Day 1 or at any time thereafter during course of the study. Subjects in the treatment groups will receive a dose of 15 mg/kg of NM8074 on Day 1, which will be administered during the study visit by the site staff. During the remainder of the treatment period, subjects will be given another 15 mg/kg dose every two weeks at approximately the same time. On days of scheduled study visits at the Investigation Site, the dose must be administered after blood work is completed.
    Primary Outcome Measure Information:
    Title
    Normalization of serum LDH(Lactate dehydrogenase) levels from baseline levels
    Time Frame
    Up to Week 12
    Title
    Change from Baseline or Percent Change from Baseline in total hemoglobin levels (g/dL)
    Time Frame
    Up to Week 12
    Title
    Change from Baseline or Percent Change from Baseline in total number of units of packed red blood cells (pRBCs) transfused through Week 12
    Time Frame
    Up to Week 12
    Title
    Change from Baseline or Percent Change from Baseline in number of transfusions
    Time Frame
    Up to Week 12
    Title
    Percent Change from Baseline in Levels of Membrane Attack Complex (MAC) via Alternative Pathway (AP) of Complement Activity as Compared to Percent Change from Baseline in Levels of MAC via Classical Pathway (CP) of Complement Activity
    Time Frame
    Up to Week 12
    Secondary Outcome Measure Information:
    Title
    Normalization of anemia
    Description
    Change from Baseline or Percent Change from Baseline in Reticulocyte Count
    Time Frame
    Up to Week 12
    Title
    Normalization of anemia
    Description
    Change from Baseline or Percent Change from Baseline in Bilirubin Levels
    Time Frame
    Up to Week 12
    Title
    Change from Baseline or Percent Change from Baseline of C3b deposition on PNH Type II and Type III RBCs via Flow Cytometry
    Time Frame
    Up to Week 12

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Male or female patients ≥ 18 years at the time of consent Confirmation of PNH diagnosis by flow cytometry evaluation of red blood cells (RBCs) and white blood cells (WBCs), with granulocyte or monocyte clone size of ~5% Presence of one or more of the following PNH-related signs or symptoms within 3 months of Screening: fatigue, hemoglobinuria, abdominal pain, shortness of breath (dyspnea), anemia: hemoglobin < 10 g/dL, history of a major adverse vascular event (including thrombosis), dysphagia, erectile dysfunction, PNH-mediated pRBC transfusions PNH patients must be undergoing treatment with Soliris for at least 3 months prior to screening, and must have a lactate dehydrogenase (LDH) level ≥ 1.5 times the upper limit of normal (ULN) during Screening Willing and able to understand and complete informed consent procedures, including signing and dating the informed consent form (ICF), and comply with the study visit schedule. Female subjects of childbearing potential must have a negative pregnancy test at Screening, and must not be planning pregnancy throughout the extent of the study term Female subjects of child-bearing potential and all male subjects must agree to use of effective contraception during study Soliris treated individuals must be able to provide documentation of vaccination against meningococcal infections. Exclusion Criteria: Platelet count < 30,000/µL at Screening Absolute neutrophil count (ANC) < 500 cells/µL at Screening Body weight < 85 lbs. (38 kg) at Screening Estimated glomerular filtration rate of < 30 mL/min/1.73m2 based on modification of diet in renal disease (MDRD) equation, creatinine clearance, or CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) at Screening Elevation of liver function tests: alanine aminotransferase (ALT) > 2xULN or direct bilirubin and alkaline phosphatase (ALP) both > 2xULN Has a known history of meningococcal disease or N. meningitidis infection Has an immunological disorder, such as, but not limited to, human immunodeficiency virus (HIV) infection (as evident by HIV-1 or HIV-2 antibody titer) or any acute or chronic infection including, but not limited to, hepatitis B virus (HBV) or hepatitis C virus (HCV) Currently active systemic infection or suspicion of active bacterial, viral, or fungal infection that requires antibiotic, antifungal, antiparasitic, or antiviral mediations Temperature > 38°C for more than two weeks prior to screening History of bone marrow or solid organ transplantation Pregnant, planning to become pregnant, or nursing female subjects Recent surgery requiring general anesthesia within the 2 weeks prior to Screening, or expected to have surgery requiring general anesthesia during the 12-week treatment period Active malignancy requiring surgery, chemotherapy, or radiation within the prior 12- months (subjects with a history of malignancy who have undergone curative resection or otherwise not requiring treatment for at least 12-months prior to screening with no detectable recurrences are allowed) History of any significant major medical conditions (cardiac, pulmonary, renal, e endocrine, or hepatic), or psychiatric disorder that, in the opinion of the Investigator, would make the subject unsuitable for participation in the study PNH patients currently under complement blocker treatments other than Soliris Concomitant use of anticoagulants is prohibited, if not on a stable regimen for at least 2 weeks prior to Day 1 Participation in any experimental small molecule or non-antibody therapy within 60 days prior to dosing on Day 1 (participation in observational studies and/or registry studies is permitted) Known or suspected history of illegal recreational drug or alcohol abuse within 1 year prior to start of screening Hypersensitivity or history of allergy to excipients in NM8074 formulation Unable or unwilling to comply with the requirements of the study
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Rekha Bansal, PhD
    Phone
    2164402696
    Email
    clinicalsae@novelmed.com

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    Study of NM8074 in Soliris-Treated Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)

    We'll reach out to this number within 24 hrs