This study will use a new investigation study drug called OMS906 in peoplewith C3 Glomerulopathy (C3G) or Idiopathic Immune Complex-Mediated Glomerulonephritis (ICGN). The purpose of this study is to test the safety and describe the effect of OMS906 study drug in people with these diseases.

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] - Immune System Diseases [C20]

Trial duration

29 Jan 2024 → 16 Apr 2026

Decision date (initial)

2024-08-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Omeros Corporation (Sponsor)

External identifiers

EU CT number

2023-508669-33-00

EudraCT number

2022-002457-26

ClinicalTrials.gov

NCT06209736

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety, Pharmacodynamic

To assess overall safety and tolerability of 5 mg/kg repeat-dose OMS906 IV administration at 4-week intervals in patients with C3G and ICGN.

Secondary objectives 7

1. To assess preliminary efficacy by change from baseline in proteinuria measured as 24-hour urine protein/creatinine ratio (UPCR) at 12, 24, and 48 weeks.
2. To assess preliminary efficacy by change from baseline in proteinuria measured as 24-hour urine protein excretion (UPE) at 12, 24, and 48 weeks.
3. To assess preliminary efficacy by change from baseline in albuminuria measured as 24-hour urine albumin/creatinine ratio (UACR) at 12, 24,and 48 weeks.
4. To assess preliminary efficacy by change from baseline in albuminuria measured as 24-hour urine albumin excretion (UAE) at 12, 24, and 48 weeks.
5. To assess preliminary efficacy by change from baseline of eGFR calculated by the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI) formula at 24 and 48 weeks.
6. To assess preliminary efficacy by change from baseline serum creatinine concentration at 24 and 48 weeks.
7. To assess PK, PD by mature (activated) complement factor D (FD), and anti-drug antibodies.

Conditions and MedDRA coding

C3 Glomerulopathy and Idiopathic Immune Complex-Mediated Glomerulonephritis

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Male or female adults 18 years and older.
2. Competent to provide informed consent and has completed informed consent procedures.
3. Diagnosis of C3G, including dense deposit disease, or ICGN confirmed by biopsy within 36 months of screening.
4. Two 24-hour UPCR ≥ 0.8 gm/gm with the 2 collections separated by 14-28 days.
5. GFR estimated by the CKD-EPI equation ≥ 30 mL/min/1.73m2.
6. Serum C3 concentration less than the lower limit of laboratory normal during the screening
7. Must be on stable maximally tolerated or allowed dose of ACE inhibitor or ARB for at least 90 days.
8. If receiving a sodium-glucose co-transporter-2 (SGLT-2) inhibitor must be on a stable dose for at least 90 days.
9. If receiving mycophenolate mofetil, a mineralocorticoid receptor antagonist, or a corticosteroid must be on stable dose for at least 90 days.
10. Have current vaccination status for Neisseria meningitidis, Streptococcus pneumonia and Haemophilus influenza (where available) and agree to maintain vaccination throughout the study. Patients who have not received these vaccinations at the time of screening may be vaccinated at any time prior to 2 weeks before the first study drug administration. Vaccine serotypes will be chosen by the local standard of care and serotype prevalence.
11. Female patients of child-bearing potential must have a negative highly sensitive pregnancy test at screening and prior to each dose of OMS906.
12. 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.
13. 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.

Exclusion criteria 19

1. History of major organ transplant or hematopoietic stem cell/marrow transplant.
2. Have known congenital deficiency of any of complement factors C1q, C1r, C1s, C2 or C4.
3. Have rapidly progressing glomerulonephritis defined as a 50% or greater decline in the eGFR within 3 months with renal biopsy findings of glomerular crescent formation seen in at least 50% of glomeruli.
4. Have renal biopsy findings showing interstitial fibrosis/tubular atrophy of more than 50%.
5. Immunodeficiency or treatment with immunosuppressive agents (except mycophenolate mofetil or corticosteroids at the prednisone equivalent of ≤ 7.5 mg/day in patients with C3G only) within 90 days of screening.
6. Treatment with rituximab within 6 months of screening.
7. Resting blood pressure > 140/90 mmHg during screening.
8. History of any active malignancy within 5 years of screening except non-melanoma skin cancers.
9. History of monoclonal gammopathy of unknown significance or any autoimmune disorder.
10. Elevation of liver function tests, defined as total bilirubin > 2 × upper limit of normal (ULN), direct bilirubin > 1.5 × ULN, and elevated transaminases, alanine aminotransferase (ALT) or aspartate aminotransferase (AST), > 2 × ULN.
11. History of any severe hypersensitivity reactions to other monoclonal antibodies or excipients included in the OMS906 preparation.
12. Significant active bacterial or viral infection within the 2 weeks prior to screening including Covid-19 infection.
13. Use of any other complement inhibitor within 6 months prior to the screening visit.
14. Have human immunodeficiency virus, hepatitis B, or untreated hepatitis C infection.
15. Pregnant, planning to become pregnant, or nursing female patient.
16. Recent surgery requiring general anesthesia within the 2 weeks prior to screening or expected to have surgery requiring general anesthesia during the treatment period.
17. 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.
18. 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.
19. 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, 12-lead electrocardiograms (ECGs), and clinical laboratory tests.

Secondary endpoints 9

1. Change from baseline in proteinuria measured as 24-hour UPCR at 12, 24, and 48 weeks.
2. Change from baseline in proteinuria measured as 24-hour UPE at 12, 24, and 48 weeks.
3. Change from baseline in proteinuria measured as 24-hour UACR at 12, 24, and 48 weeks.
4. Change from baseline in proteinuria measured as 24-hour urine UAE at 12, 24, and 48 weeks.
5. Change from baseline of eGFR calculated by the CKD-EPI formula at 24 and 48 weeks.
6. Change from baseline in serum creatinine at 24 and 48 weeks.
7. Key OMS906 PK parameters estimated using appropriate population PK methods based on sparse sampling.
8. Serum/plasma PD parameters, including mature FD, measured as changes from baseline.
9. Incidence of ADAs in serum.

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

Steve Whitaker

Public contact point

Organisation

Omeros Corp.

Contact name

Omeros Clinical Trial Admin

Third parties 3

Locations

2 EU/EEA countries · 3 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 16 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