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Safety and Efficacy of OMS906 in Paroxysmal Nocturnal Hemoglobinuria Patients With a Sub-optimal Response to Ravulizumab

Primary Purpose

Paroxysmal Nocturnal Hemoglobinuria

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
OMS906 Study Drug - 3 mg/kg
OMS906 Study Drug - 5 mg/kg
Ravulizumab
Sponsored by
Omeros Corporation
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Paroxysmal Nocturnal Hemoglobinuria focused on measuring PNH

Eligibility Criteria

18 Years - 99 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Confirmed diagnosis of PNH by flow cytometry with PNH clone size of > 10% red blood cells (RBCs) and/or granulocytes. Male or female adults 18 years and older. Completed informed consent procedures. In relation to ravulizumab treatment prescribed in accordance with its marketing authorization and summary of product characteristics (SmPC): • Must have a sub-optimal response to ravulizumab, defined as a hemoglobin level < 10.5 g/dL despite treatment measured at screening and confirmed at baseline (Day 1, predose). Ravulizumab treatment will have been maintained at a stable dose for at least 2 doses (4 months) prior to baseline. Female patients of child-bearing potential must have a negative highly sensitive urine pregnancy test at screening and prior to each dose of OMS906. Females must use highly effective birth control to prevent pregnancy during the clinical trial and for 20 weeks (140 days) following their last dose of study drug. If a female, must be sterile (either surgically or biologically)* or at least one year postmenopausal**, or have a monogamous partner who is surgically sterile, or have a same sex partner, or if in a heterosexual relationship, must agree to comply with the following contraception guidelines: Practice abstinence (only considered an acceptable method of contraception when it is in line with the patients' usual and preferred lifestyle and the patient agrees to refrain from heterosexual intercourse during the entire period of risk associated with the study treatments, including during the clinical trial and for 20 weeks [140 days] following their last dose of study drug), or Use at least 1 of the following medically acceptable methods of birth control: Hormonal methods as follows: Combined estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal). Progestogen only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) Intrauterine devices Intrauterine hormone-releasing systems Vasectomized partner * Defined as having had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; or have a congenital or acquired condition that prevents childbearing. Defined as at least 12 months with no menses without an alternative medical cause) [can be confirmed with follicle stimulating hormone level (FSH) in the postmenopausal range (FSH levels ≥40 milli-International unit (mIU)/mL at Screening) if the patient is not using hormonal contraception or on hormonal replacement therapy]. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. Males must use highly effective birth control with a female partner to prevent pregnancy during the clinical trial and for 20 weeks (140 days) following their last dose of study drug that include the following: Practice abstinence (only considered an acceptable method of contraception when it is in line with the patients' usual and preferred lifestyle and the patient agrees to refrain from heterosexual intercourse during the entire period of risk associated with the study treatments, including during the clinical trial and for 20 weeks [140 days] following their last dose of study drug), or Use (or have their partner use) acceptable, highly effective contraception (see Criterion #6) during heterosexual activity. Exclusion Criteria: History of major organ transplant or hematopoietic stem cell/marrow transplant. Platelet count < 30,000/µL or absolute neutrophil count < 500 cells/µL at Screening. Anemia, as evidenced by hemoglobin < 10.5 g/dL, attributable to any other medical condition apart from PNH. Elevation of liver function tests, defined as total bilirubin > 2×ULN, direct bilirubin > 1.5× upper limit of normal (ULN), and elevated transaminases, alanine aminotransferase (ALT) or aspartate aminotransferase (AST), > 2×ULN unless due to PNH related hemolysis. History of any severe hypersensitivity reactions to other monoclonal antibodies or excipients included in the OMS906 preparation. Significant active bacterial or viral infection within the 2 weeks prior to Screening, including COVID-19 infection. Immunodeficiency or immunosuppression (including chronic use of immunosuppressive drugs, such as ciclosporin or tacrolimus). History of meningococcal disease and/or has not received vaccination for N. meningitidis. Pregnant, planning to become pregnant, or nursing female patients. Recent surgery requiring general anesthesia within the 2 weeks prior to Screening or expected to have surgery requiring general anesthesia during the Treatment Period. History of any significant medical, neurologic, or psychiatric disorder that in the opinion of the Investigator would make the patient unsuitable for participation in the study. Treatment with any investigational medicinal product or investigational device within 30 days (or within 5× its half-life in days, whichever is the longer period) prior to Screening, or participation in another concurrent clinical trial involving a therapeutic intervention. Participation in observational and/or registry studies is permitted. Unable or unwilling to comply with the requirements of the study.

Sites / Locations

  • Omeros Investigational SiteRecruiting
  • Omeros Investigational SiteRecruiting
  • Omeros Investigational SiteRecruiting
  • Omeros Investigational SiteRecruiting
  • Omeros Investigational SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

OMS906 Study Drug - 3 mg/kg IV with Ravulizumab IV

OMS906 Study Drug - 5 mg/kg IV with Ravulizumab IV

Arm Description

Up to 6 doses of 3 mg/kg at 8-week intervals

Up to 6 doses of 5 mg/kg at 8-week intervals

Outcomes

Primary Outcome Measures

To assess the overall OMS906 administration at 8-week intervals in PNH patients.
Number and % of participants with Treatment-emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0, including abnormalities in laboratory measures, ECGs and physical examinations

Secondary Outcome Measures

Incidence of patients with hemoglobin increase ≥ 2.0 g/dL from baseline (Response criterion) baseline on adjunctive treatment and sustained during monotherapy.
Number and % of participants with hemoglobin increase ≥ 2.0 g/dL from baseline on adjunctive treatment and sustained during monotherapy
Reticulocyte count
Individual patient changes from baseline in absolute reticulocyte counts
Lactate dehydrogenase (LDH)
Individual patient changes from baseline in LDH
Transfusion requirements
Number of transfusions required during each treatment phase will be compared with the transfusion history prior to the study
Pharmacokinetics (PK) of multiple-dose administration of OMS906
PK parameters including OMS906 maximum concentration (Cmax) and Area under the plasma concentration versus time curve (AUC)
Pharmacodynamics (PD) of multiple-dose administration of OMS906
Mature Complement Factor D (CFD) concentration
OMS906 anti-drug antibodies (ADA)
Number of patients with measurable ADA

Full Information

First Posted
July 11, 2023
Last Updated
July 25, 2023
Sponsor
Omeros Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT05972967
Brief Title
Safety and Efficacy of OMS906 in Paroxysmal Nocturnal Hemoglobinuria Patients With a Sub-optimal Response to Ravulizumab
Official Title
A Phase 1b Proof of Concept Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of OMS906 in PNH Patients With a Sub-optimal Response to the C5 Inhibitor, Ravulizumab
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 27, 2023 (Actual)
Primary Completion Date
May 31, 2025 (Anticipated)
Study Completion Date
July 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Omeros Corporation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of OMS906 for the treatment of Paroxysmal Nocturnal Hemoglobinuria (PNH) in patients who have a sub-optimal response to ravulizumab.
Detailed Description
This is a Phase 1b, proof of concept, open label study examining two doses of OMS906, 3 mg/kg and 5 mg/kg IV given to PNH patients at 8-week intervals, first in combination with the C5 inhibitor ravulizumab then as monotherapy. The primary objective is to assess overall safety and tolerability of repeat-dose IV OMS906 administration at 8-week intervals in patients with PNH.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
OMS906 Study Drug - 3 mg/kg IV with Ravulizumab IV
Arm Type
Experimental
Arm Description
Up to 6 doses of 3 mg/kg at 8-week intervals
Arm Title
OMS906 Study Drug - 5 mg/kg IV with Ravulizumab IV
Arm Type
Experimental
Arm Description
Up to 6 doses of 5 mg/kg at 8-week intervals
Intervention Type
Drug
Intervention Name(s)
OMS906 Study Drug - 3 mg/kg
Intervention Description
All patients will receive 3 doses of OMS906 of 3 mg/kg Intravenous (IV) at 8-week intervals. Clinical responders at Week 24 will receive an additional 3 doses of OMS906 only at 8-week intervals (monotherapy). Incomplete responders may receive an additional 3 doses of OMS906 with ravulizumab at 8-week intervals. Non responders will not receive additional OMS906.
Intervention Type
Drug
Intervention Name(s)
OMS906 Study Drug - 5 mg/kg
Intervention Description
All patients will receive 3 doses of OMS906 of 5 mg/kg Intravenous (IV) at 8-week intervals. Clinical responders at Week 24 will receive an additional 3 doses of OMS906 only at 8-week intervals (monotherapy). Incomplete responders may receive an additional 3 doses of OMS906 with ravulizumab at 8-week intervals. Non responders will not receive additional OMS906.
Intervention Type
Drug
Intervention Name(s)
Ravulizumab
Intervention Description
Participants must be on prescribed stable dose of ravulizumab (IV dose per approved summary of medicinal product characteristics) for at least 2 doses (4 months) prior to baseline. During the Run-in period - ravulizumab only. During the Treatment period all patients will receive 3 doses of ravulizumab at 8-week intervals. Clinical responders at Week 24 will not receive additional ravulizumab. Incomplete responders may receive an additional 3 doses of ravulizumab with OMS906 at 8-week intervals. Non responders will return to treatment with ravulizumab or standard of care.
Primary Outcome Measure Information:
Title
To assess the overall OMS906 administration at 8-week intervals in PNH patients.
Description
Number and % of participants with Treatment-emergent Adverse Events (TEAEs) as assessed by CTCAE v5.0, including abnormalities in laboratory measures, ECGs and physical examinations
Time Frame
56 weeks
Secondary Outcome Measure Information:
Title
Incidence of patients with hemoglobin increase ≥ 2.0 g/dL from baseline (Response criterion) baseline on adjunctive treatment and sustained during monotherapy.
Description
Number and % of participants with hemoglobin increase ≥ 2.0 g/dL from baseline on adjunctive treatment and sustained during monotherapy
Time Frame
56 weeks
Title
Reticulocyte count
Description
Individual patient changes from baseline in absolute reticulocyte counts
Time Frame
56 weeks
Title
Lactate dehydrogenase (LDH)
Description
Individual patient changes from baseline in LDH
Time Frame
56 weeks
Title
Transfusion requirements
Description
Number of transfusions required during each treatment phase will be compared with the transfusion history prior to the study
Time Frame
56 weeks
Title
Pharmacokinetics (PK) of multiple-dose administration of OMS906
Description
PK parameters including OMS906 maximum concentration (Cmax) and Area under the plasma concentration versus time curve (AUC)
Time Frame
56 weeks
Title
Pharmacodynamics (PD) of multiple-dose administration of OMS906
Description
Mature Complement Factor D (CFD) concentration
Time Frame
56 weeks
Title
OMS906 anti-drug antibodies (ADA)
Description
Number of patients with measurable ADA
Time Frame
56 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Confirmed diagnosis of PNH by flow cytometry with PNH clone size of > 10% red blood cells (RBCs) and/or granulocytes. Male or female adults 18 years and older. Completed informed consent procedures. In relation to ravulizumab treatment prescribed in accordance with its marketing authorization and summary of product characteristics (SmPC): • Must have a sub-optimal response to ravulizumab, defined as a hemoglobin level < 10.5 g/dL despite treatment measured at screening and confirmed at baseline (Day 1, predose). Ravulizumab treatment will have been maintained at a stable dose for at least 2 doses (4 months) prior to baseline. Female patients of child-bearing potential must have a negative highly sensitive urine pregnancy test at screening and prior to each dose of OMS906. Females must use highly effective birth control to prevent pregnancy during the clinical trial and for 20 weeks (140 days) following their last dose of study drug. If a female, must be sterile (either surgically or biologically)* or at least one year postmenopausal**, or have a monogamous partner who is surgically sterile, or have a same sex partner, or if in a heterosexual relationship, must agree to comply with the following contraception guidelines: Practice abstinence (only considered an acceptable method of contraception when it is in line with the patients' usual and preferred lifestyle and the patient agrees to refrain from heterosexual intercourse during the entire period of risk associated with the study treatments, including during the clinical trial and for 20 weeks [140 days] following their last dose of study drug), or Use at least 1 of the following medically acceptable methods of birth control: Hormonal methods as follows: Combined estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal). Progestogen only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) Intrauterine devices Intrauterine hormone-releasing systems Vasectomized partner * Defined as having had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion at least 6 weeks prior to screening; or have a congenital or acquired condition that prevents childbearing. Defined as at least 12 months with no menses without an alternative medical cause) [can be confirmed with follicle stimulating hormone level (FSH) in the postmenopausal range (FSH levels ≥40 milli-International unit (mIU)/mL at Screening) if the patient is not using hormonal contraception or on hormonal replacement therapy]. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. Males must use highly effective birth control with a female partner to prevent pregnancy during the clinical trial and for 20 weeks (140 days) following their last dose of study drug that include the following: Practice abstinence (only considered an acceptable method of contraception when it is in line with the patients' usual and preferred lifestyle and the patient agrees to refrain from heterosexual intercourse during the entire period of risk associated with the study treatments, including during the clinical trial and for 20 weeks [140 days] following their last dose of study drug), or Use (or have their partner use) acceptable, highly effective contraception (see Criterion #6) during heterosexual activity. Exclusion Criteria: History of major organ transplant or hematopoietic stem cell/marrow transplant. Platelet count < 30,000/µL or absolute neutrophil count < 500 cells/µL at Screening. Anemia, as evidenced by hemoglobin < 10.5 g/dL, attributable to any other medical condition apart from PNH. Elevation of liver function tests, defined as total bilirubin > 2×ULN, direct bilirubin > 1.5× upper limit of normal (ULN), and elevated transaminases, alanine aminotransferase (ALT) or aspartate aminotransferase (AST), > 2×ULN unless due to PNH related hemolysis. History of any severe hypersensitivity reactions to other monoclonal antibodies or excipients included in the OMS906 preparation. Significant active bacterial or viral infection within the 2 weeks prior to Screening, including COVID-19 infection. Immunodeficiency or immunosuppression (including chronic use of immunosuppressive drugs, such as ciclosporin or tacrolimus). History of meningococcal disease and/or has not received vaccination for N. meningitidis. Pregnant, planning to become pregnant, or nursing female patients. Recent surgery requiring general anesthesia within the 2 weeks prior to Screening or expected to have surgery requiring general anesthesia during the Treatment Period. History of any significant medical, neurologic, or psychiatric disorder that in the opinion of the Investigator would make the patient unsuitable for participation in the study. Treatment with any investigational medicinal product or investigational device within 30 days (or within 5× its half-life in days, whichever is the longer period) prior to Screening, or participation in another concurrent clinical trial involving a therapeutic intervention. Participation in observational and/or registry studies is permitted. Unable or unwilling to comply with the requirements of the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Omeros Clinical Trial Information
Phone
206-676-5000
Email
ctinfo@omeros.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edward Philpot, MD
Organizational Affiliation
Omeros Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Omeros Investigational Site
City
Aachen
Country
Germany
Individual Site Status
Recruiting
Facility Name
Omeros Investigational Site
City
Ulm
Country
Germany
Individual Site Status
Recruiting
Facility Name
Omeros Investigational Site
City
Thessaloniki
Country
Greece
Individual Site Status
Recruiting
Facility Name
Omeros Investigational Site
City
Lausanne
Country
Switzerland
Individual Site Status
Recruiting
Facility Name
Omeros Investigational Site
City
Leeds
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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Safety and Efficacy of OMS906 in Paroxysmal Nocturnal Hemoglobinuria Patients With a Sub-optimal Response to Ravulizumab

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