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

• ClinicalTrials.gov Identifier: NCT05972967
• Recruitment Status: Recruiting
• First Posted: August 2, 2023
• Last Update Posted: August 2, 2023
• Sponsor: Omeros Corporation
• Information provided by (Responsible Party): Omeros Corporation

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.

Condition or disease	Intervention/treatment	Phase
Paroxysmal Nocturnal Hemoglobinuria	Drug: OMS906 Study Drug - 3 mg/kg; Drug: OMS906 Study Drug - 5 mg/kg; Drug: Ravulizumab	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: March 27, 2023
• Estimated Primary Completion Date: May 31, 2025
• Estimated Study Completion Date: July 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: OMS906 Study Drug - 3 mg/kg IV with Ravulizumab IV; Up to 6 doses of 3 mg/kg at 8-week intervals	Drug: OMS906 Study Drug - 3 mg/kg; 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.; Drug: Ravulizumab; 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.
Experimental: OMS906 Study Drug - 5 mg/kg IV with Ravulizumab IV; Up to 6 doses of 5 mg/kg at 8-week intervals	Drug: OMS906 Study Drug - 5 mg/kg; 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.; Drug: Ravulizumab; 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.

Outcome Measures

Primary Outcome Measures :

1. To assess the overall OMS906 administration at 8-week intervals in PNH patients. [ Time Frame: 56 weeks ]
   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 :

1. Incidence of patients with hemoglobin increase ≥ 2.0 g/dL from baseline (Response criterion) baseline on adjunctive treatment and sustained during monotherapy. [ Time Frame: 56 weeks ]
   Number and % of participants with hemoglobin increase ≥ 2.0 g/dL from baseline on adjunctive treatment and sustained during monotherapy
2. Reticulocyte count [ Time Frame: 56 weeks ]
   Individual patient changes from baseline in absolute reticulocyte counts
3. Lactate dehydrogenase (LDH) [ Time Frame: 56 weeks ]
   Individual patient changes from baseline in LDH
4. Transfusion requirements [ Time Frame: 56 weeks ]
   Number of transfusions required during each treatment phase will be compared with the transfusion history prior to the study
5. Pharmacokinetics (PK) of multiple-dose administration of OMS906 [ Time Frame: 56 weeks ]
   PK parameters including OMS906 maximum concentration (Cmax) and Area under the plasma concentration versus time curve (AUC)
6. Pharmacodynamics (PD) of multiple-dose administration of OMS906 [ Time Frame: 56 weeks ]
   Mature Complement Factor D (CFD) concentration
7. OMS906 anti-drug antibodies (ADA) [ Time Frame: 56 weeks ]
   Number of patients with measurable ADA

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Confirmed diagnosis of PNH by flow cytometry with PNH clone size of > 10% red blood cells (RBCs) and/or granulocytes.
2. Male or female adults 18 years and older.
3. Completed informed consent procedures.

4. 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.

5. Female patients of child-bearing potential must have a negative highly sensitive urine pregnancy test at screening and prior to each dose of OMS906.

6. 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.

7. 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:

1. History of major organ transplant or hematopoietic stem cell/marrow transplant.
2. Platelet count < 30,000/µL or absolute neutrophil count < 500 cells/µL at Screening.
3. Anemia, as evidenced by hemoglobin < 10.5 g/dL, attributable to any other medical condition apart from PNH.
4. 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.
5. History of any severe hypersensitivity reactions to other monoclonal antibodies or excipients included in the OMS906 preparation.
6. Significant active bacterial or viral infection within the 2 weeks prior to Screening, including COVID-19 infection.
7. Immunodeficiency or immunosuppression (including chronic use of immunosuppressive drugs, such as ciclosporin or tacrolimus).
8. History of meningococcal disease and/or has not received vaccination for N. meningitidis.
9. Pregnant, planning to become pregnant, or nursing female patients.
10. Recent surgery requiring general anesthesia within the 2 weeks prior to Screening or expected to have surgery requiring general anesthesia during the Treatment Period.
11. 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.
12. 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.
13. Unable or unwilling to comply with the requirements of the study.

Contacts and Locations

Contacts

Contact: Omeros Clinical Trial Information; 206-676-5000; ctinfo@omeros.com

Locations

Germany

Omeros Investigational Site; Recruiting

Aachen, Germany

Omeros Investigational Site; Recruiting

Ulm, Germany

Greece

Omeros Investigational Site; Recruiting

Thessaloniki, Greece

Switzerland

Omeros Investigational Site; Recruiting

Lausanne, Switzerland

United Kingdom

Omeros Investigational Site; Recruiting

Leeds, United Kingdom

Sponsors and Collaborators

Omeros Corporation

Investigators

• Study Director: Edward Philpot, MD; Omeros Corporation

More Information

• Responsible Party: Omeros Corporation
• ClinicalTrials.gov Identifier: NCT05972967
• Other Study ID Numbers: OMS906-PNH-001
• First Posted: August 2, 2023
• Last Update Posted: August 2, 2023
• Last Verified: July 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Omeros Corporation:

PNH

Additional relevant MeSH terms:

Hemoglobinuria; Hemoglobinuria, Paroxysmal; Proteinuria; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Anemia, Hemolytic; Anemia; Hematologic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases; Ravulizumab; Complement Inactivating Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs