C3G, IgAN, LN, MN
Conditions
Keywords
Immunoglobulin A Nephropathy, Lupus Nephritis, Membranous Nephropathy, Complement Component 3 Glomerulopathy
Brief summary
The purpose of this study was to evaluate the safety and tolerability of OMS721 (narsoplimab) in participants with Immunoglobulin A Nephropathy (IgAN), Lupus Nephritis (LN), Membranous Nephropathy (MN), and Complement Component 3 Glomerulopathy (C3G) including Dense Deposit Disease. The study will also evaluate Pharmacokinetics (PK), Pharmacodynamics (PD), anti-drug antibody response (ADA), and neutralizing antibodies (NAb) of narsoplimab when administered intravenously and when administered both intravenously and subcutaneously in participants of Asian descent with IgA Nephropathy.
Interventions
BIOLOGICALOMS721 (narsoplimab)
Biological: narsoplimab
Sponsors
Omeros Corporation
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
Cohort 2 and 3 participants were randomized in a 1:1 fashion during the first 12 weeks of treatment. Cohort 1 and 4 studies were both open-label studies.
Intervention model description
Double blind vehicle controlled interventional study with open label period (Cohort 2 and 3) and strictly open-label studies (Cohort 1 and 4) Cohort 2 and 3 subjects were randomized in a 1:1 fashion during the first 12 weeks of treatment. Cohort 1 and 4 studies were both open-label studies.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Participants may be included in the study only if they meet all of the following criteria: 1. Have a diagnosis of one of the following: * IgAN diagnosed on kidney biopsy * Lupus nephritis diagnosed on kidney biopsy (Cohort 1 only) * Primary MN diagnosed on kidney biopsy (Cohort 1 only) * C3 glomerulopathy including Dense Deposit Disease diagnosed on kidney biopsy (Cohort 1 only) * Biopsy confirmed diagnosis of IgAN within 8 years of screening (Cohort 4 only). 2. Have 24-hour urine protein \> 1000 mg/24 hours. 3. Are age \>= 18 years at Screening Visit 1 and (for Cohort 4 only) are of Asian descent. 4. Have documented history of 24-hour urine protein \> 1 g within 6 months prior to Screening or Urine Protein Creatinine Ratio (uPCR) \> 0.75 by spot urine at Screening (Cohort 4 only). 5. Have an eGFR \> 30 mL/min/1.73 m\^2 calculated by the Chronic Kidney Disease Epidemiology (CKD-EPI) equation at Screening (Cohort 4). 6. Are on physician-directed, stable, optimized treatment with ACEIs and/or ARBs and have a systolic BP of \< 150 mmHg and a diastolic BP of \< 90 mmHg at rest. 7. If female, are either a) not of childbearing potential (i.e., surgically sterilized or postmenopausal for \> 1 year), b) have a negative pregnancy test at Screening and baseline and if sexually active must agree to use 2 medically reliable forms of contraception throughout the study (all Cohorts) and for at least 12 weeks after the last dose of study drug, including possible extended treatments (Cohort 4), or c) have a medically sterilized male partner. Acceptable methods of contraception include a reliable intrauterine device, hormonal contraception, or a barrier method. 8. If male having heterosexual intercourse, are either a) not of reproductive potential or b) if sexually active must agree to use a medically reliable form of contraception throughout the study (all Cohorts) and for at least 12 weeks after the last dose of study drug, including possible extended treatments (Cohort 4). Acceptable methods of birth control include spermicide in combination with a barrier method, or subject's female partner is willing to use medically acceptable methods of birth control (intrauterine device, hormonal contraception, or a barrier method).
Exclusion criteria
1. Have a known hypersensitivity to any constituent of the investigational product. 2. Have a hemoglobin \< 9.0 g/dL. 3. Have a platelet count \< 100,000/mm\^3. 4. Have an absolute neutrophil count \< 500 cells/mm\^3. 5. Have an alanine aminotransferase or aspartate aminotransferase \> 5.0 x the upper limit of normal. 6. Have systemic manifestations of Henoch-Schonlein purpura (e.g., joint pain, gastrointestinal bleeding, abdominal pain) within 2 years prior to Screening Visit 1. 7. Have used belimumab, eculizumab, or rituximab within 6 months of Screening Visit 1. 8. Treatment with immunosuppressants (e.g., azathioprine or cyclophosphamide), or cytotoxic drugs, for IgAN within 8 weeks prior to Screening. Treatment with immunosuppressants or cytotoxic drugs for IgAN is not allowed during the Run-In Period. Treatment with immunosuppressants are allowed if such treatment is for indications other than IgAN(Cohort 4 only). 9. Have a history of renal transplant. 10. History of human immunodeficiency virus, evidence of immune suppression, active hepatitis C virus (HCV) infection (participants with positive anti-HCV antibody but a non-detected HCV RNA PCR can enroll), hepatitis B virus (HBV) infection (participants with positive HBsAg are excluded. For participants with isolated positive anti-HBc antibody, HBV DNA test by PCR must be non-detectable to enroll). 11. Have any significant infection requiring antibiotic treatment at Screening Visit 1. 12. Have a malignancy except for adequately treated and cured basal or squamous cell skin cancer, curatively treated in situ disease, or other cancer from which the subject has been disease-free for \>=5 years. 13. Have an expectation of survival of less than 24 months. 14. If female, are pregnant or breastfeeding. 15. Have received any other investigational drug or device or experimental procedures within 30 days of Screening Visit 1. 16. Are an employee of Omeros, the investigative site, a study staff member, or their immediate family member. 17. Have any condition that the Investigator believes would put the subject at risk from participation. 18. For participants in Cohort 4, have received systemic corticosteroids within 8 weeks prior to Screening. Treatment with systemic corticosteroids is not allowed during the Run-In period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 1-3: Proportion of IgAN, LN, MN, C3 Glomerulopathy Participants With Treatment Related Adverse Events (AE). | up to 104 weeks | Proportion of participants with Treatment Related Adverse Events (AE). |
| Cohort 4: Proportion of IgAN Participants of Asian Descent With Treatment Related AEs. | 38 weeks | Proportion of participants with Treatment Related Adverse Events (AE). |
| Cohort 4: Change From Baseline in Serum and Urine Complement Component Levels. | 38 weeks | Concentrations of urine complement components |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cohort 1-3: Absolute Change From Baseline in Serum Narsoplimab Concentrations (ng/mL). | up to 104 weeks | Pharmacokinetics (PK): Maximum plasma concentrations (Cmax) |
| Cohort 4: Change From Baseline in Serum Narsoplimab Concentrations. | 38 weeks | Pharmacokinetics (PK): Maximum plasma concentrations (Cmax) |
| Cohort 1-3: Change From Baseline in Urine Protein Excretion (UPE) mg/24hrs. | up to 120 days | Change from Baseline in Urine Protein Excretion (UPE) in mg/24s up to Day 120 |
| Cohort 1-3: Change From Baseline in Urine Albumin/Creatinine Ratio. | up to 104 weeks | Change From Baseline in Urine Albumin/Creatinine Ratio (mg/g) in OMS721 subjects at Day 120. Data was displayed for up to 120 days, because some patients received retreatment afterwards. |
Countries
Hong Kong, United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 30 Participants |
| Age, Continuous | 41.5 years STANDARD_DEVIATION 13.32 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 5 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 5 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 20 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 21 Participants |
| Region of Enrollment Hong Kong | 0 Participants |
| Region of Enrollment United States | 29 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 2 | 0 / 1 | 0 / 6 | 0 / 6 | 0 / 2 | 0 / 15 |
| other Total, other adverse events | 13 / 14 | 2 / 2 | 1 / 1 | 5 / 6 | 4 / 6 | 1 / 2 | 14 / 15 |
| serious Total, serious adverse events | 1 / 14 | 0 / 2 | 0 / 1 | 0 / 6 | 1 / 6 | 0 / 2 | 2 / 15 |
Outcome results
None listed