Study of NM8074 in Soliris-Treated Patients With Paroxysm... | NCT05731050

NCT05731050

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

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No data is available for this block.

Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
NM8074	Experimental	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.	Drug: NM8074

Interventions

Name	Type	Description	Arm Group Labels	Other Names
NM8074	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Normalization of serum LDH(Lactate dehydrogenase) levels from baseline levels		Up to Week 12
Change from Baseline or Percent Change from Baseline in total hemoglobin levels (g/dL)		Up to Week 12
Change from Baseline or Percent Change from Baseline in total number of units of packed red blood cells (pRBCs) transfused through Week 12		Up to Week 12
Change from Baseline or Percent Change from Baseline in number of transfusions		Up to Week 12
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		Up to Week 12

Secondary Outcomes

Measure	Description	Time Frame
Normalization of anemia	Change from Baseline or Percent Change from Baseline in Reticulocyte Count	Up to Week 12
Normalization of anemia	Change from Baseline or Percent Change from Baseline in Bilirubin Levels

Eligibility Module

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

ID	Term
D000743	Anemia, Hemolytic
D000740	Anemia
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases