An Open-Label Study to Evaluate the Long-Term Safety, Tolerability and Efficacy of OMS906 in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Omeros Corp.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

16 Jul 2024 → ongoing

Decision date (initial)

2024-05-08

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Omeros Corporation

External identifiers

EU CT number

2023-507413-10-00

ISRCTN

ISRCTN73211658

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety, Pharmacokinetic, Pharmacodynamic

To assess long-term safety and tolerability of repeat-dose zaltenibart 5 mg/kg IV and 8 mg/Kg IV
administration at 8-week intervals in patients with PNH.

Secondary objectives 1

1. To assess long-term efficacy by the effect on hemolysis and anemia measured by hemoglobin Hb, LDH, absolute reticulocyte count, and red blood cell (RBC) transfusion burden; to assess the incidence of breakthrough hemolysis; to assess zaltenibart population pharmacokinetics (PK) and the effect of zaltenibart on pharmacodynamics (PD) parameters; to assess anti-drug antibodies (ADAs); to assess the effect of zaltenibart on Quality of Life.

Conditions and MedDRA coding

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Have completed the last dosing visit of the prior OMS906-PNH-001 and OMS906-PNH-002 studies. Patients who have tolerated zaltenibart well and had an adequate clinical response will be eligible.
2. Female patients of child-bearing potential (CBP) must have a negative result from a highly sensitive urine pregnancy test prior to each dose of zaltenibart.
3. 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 a highly effective method of contraception when it is in line with the patient’s 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 highly effective methods of birth control: hormonal methods (combined estrogen-andprogestogen- containing hormonal contraception associated with inhibition of ovulation [oral, intravaginal, transdermal] or progestogen only hormonal contraception associated with inhibition of ovulation [oral, injectable, implantable]), intrauterine devices, intrauterine hormone-releasing systems, bilateral salpingectomy or bilateral tubal ligation/occlusion, or a vasectomized partner. * Defined as having had a hysterectomy and/or bilateral oophorectomy at least 6 weeks prior to the Evaluation Period; or have a congenital or acquired condition that prevents child-bearing. ** Defined as at least 12 months with no menses without an alternative medical cause (confirmed with follicle stimulating hormone level [FSH] in the postmenopausal range [FSH levels ≥ 40 mIU/mL during the Evaluation Period] 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.
4. 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 a highly effective method of contraception when it is in line with the patient's 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) highly effective contraception (see Criterion #3) during heterosexual activity.
5. Have current vaccination status for Neisseria meningitidis, Streptococcus pneumonia and Haemophilus influenzae (for S. pneumoniae and H. influenzae vacination, if locally available and/or part of standard of care) and agree to maintain vaccination throughout the study.
6. Have provided informed consent.

Exclusion criteria 7

1. Platelet count < 30,000/μL or absolute neutrophil count < 500 cells/μL at the start of the Evaluation Period.
2. Elevation of liver function tests: any single parameter of alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), or alkaline phosphatase (ALP) must not exceed 3 × ULN
3. History of any severe hypersensitivity reactions to other monoclonal antibodies or excipients included in the zaltenibart preparation.
4. Patients with unresolved serious infections caused by encapsulated bacteria including H. influenzae, S. pneumoniae and N. meningitidis.
5. Pregnant, planning to become pregnant, or nursing female patients.
6. 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 long-term extension study.
7. Unable or unwilling to comply with the requirements of the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety and tolerability as assessed by adverse events (AEs), vital signs, electrocardiograms (ECGs), and clinical laboratory tests.

Secondary endpoints 1

1. Efficacy as measured by: proportion of patients achieving Hb ≥ 12.0 g/dL assessed at 6-month intervals; proportion of patients maintaining an increase in Hb ≥ 2 g/dL, achieved in the prior study; proportion of patients who are transfusion free at Weeks 48 and 96; proportion of patients experiencing clinical BTH at Weeks 48 and 96; mean LDH and absolute reticulocyte changes from from baseline, start of the long-term extension, at Weeks 48 and 96; zaltenibart PK concentrations and PD parameters

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Omeros Corp.

Sponsor organisation

Omeros Corp.

Address

201 Elliott Avenue West

City

Seattle

Postcode

98119-4240

Country

United States

Scientific contact point

Organisation

Omeros Corp.

Contact name

William Pullman

Public contact point

Organisation

Omeros Corp.

Contact name

Victoria Chinnell

Third parties 10

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications