Immunoglobulin A (IgA) Nephropathy
Conditions
Keywords
Kidney Disease, Urologic Disease, Glomerular Disease, Berger Disease, Glomerulonephritis, IGA
Brief summary
Randomized, placebo-controlled, multi-center, double-blind, proof of concept phase IIa trial and dose evaluation trial of felzartamab in IgAN
Detailed description
Study Sponsor, originally HI-Bio, Inc., is now HI-Bio, A Biogen Company.
Interventions
DRUGFelzartamab
anti-CD38+ monoclonal antibody
OTHERPlacebo
Placebo comparator
Sponsors
HI-Bio, A Biogen Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Patients ≥ 18 to ≤ 80 years (at date of signing the informed consent form \[ICF\]), but at least of legal age in the given country * Biopsy confirmed diagnosis of IgAN within the past 8 years prior to signature of the ICF * Proteinuria at screening visit ≥ 1.0 g/d. * Treatment with an angiotensin-converting enzyme inhibitor (ACEi) and/or angiotensin receptor blocker (ARB) at maximum doses or maximally tolerated doses for ≥ 3 months prior to date of informed consent and adequate blood pressure (BP) control. * A female of childbearing potential (FCBP), is only eligible to participate if she is not pregnant, not breast feeding, and agrees to follow the contraceptive guidance during the treatment period and for at least 3 months after the last dose of IMP Key
Exclusion criteria
* Hemoglobin \< 90 g/L * Thrombocytopenia: Platelets \< 100.0 x 10\^9/L. * Neutropenia: Neutrophils \< 1.5 x 10\^9/L. * Leukopenia: Leukocytes \< 3.0 x 10\^9/L * Diabetes mellitus type 1 * Aspartate aminotransferase or alanine aminotransferase \>1.5 x ULN, alkaline phosphatase \>3.0 x ULN
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Relative Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) in 24-hour Urine at Month 9 | Baseline, Month 9 | Proteinuria is high levels of protein in the urine and is measured by UPCR. Relative change in UPCR was estimated based on mixed effects model for repeated measure (MMRM) model. Least squares (LS) mean and standard error (SE) were reported. The reference proteinuria value before start of treatment is defined as the mean of the values determined at screening and prior to baseline (visit 2) predose (UPCR from 24h urine). Negative change from baseline indicates less proteinuria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Integrative Analysis of Several Endpoints: Percent Change From Baseline in Immunoglobulin A (IgA) Concentration by Predose Serum Concentration (Ctrough) Group | Up to 9 months | All felzartamab and placebo-treated participants with evaluable IgA data and felzartamab serum concentrations (in felzartamab-treated participants only) were divided into exposure quartiles using the sum of measurable felzartamab Ctrough values up to 9 months after the first dose. Percent change from baseline in IgA concentration in these participants was summarized as per each serum concentration quartile. |
| Integrative Analysis of Several Endpoints: Maximum Serum Concentrations (Cmax) as Per the Infusion-Related Reactions (IRRs) After the First Dose | Up to 1 week | All participants with evaluable maximum felzartamab concentrations after the first dose were included in the analysis. Cmax values were assessed by infusion-related reaction status after the first dose. |
| Part 1: Relative Change From Baseline in UPCR in 24-hour Urine at Months 3, 6, 12, 18 and 24 | Baseline, Months 3,6,12,18 and 24 | Proteinuria is high levels of protein in the urine and is measured by UPCR. Relative change in UPCR will be estimated based on an MMRM model. The reference proteinuria value before start of treatment is defined as the mean of the values determined at screening and prior to baseline (visit 2) predose (UPCR from 24h urine). Negative change from baseline indicates less proteinuria. |
| Part 1: Number of Participants With Complete Response (CR) at Months 3, 6, 9, 12, 18 and 24 | Months 3,6,9,12,18 and 24 | CR was defined as the reduction of proteinuria to less than 0.3 g/g UPCR, serum albumin within the reference range of the central laboratory and stable estimated glomerular filtration rate (eGFR) (at least 80% of value at baseline visit). |
| Part 1: Percentage of Participants With Response at Months 3, 6, 9, 12, 18 and 24 | Months 3,6,9,12,18 and 24 | Response was defined as reduction of proteinuria to below 0.6 g/g (UPCR) and stable eGFR (at least 80% of value at baseline visit), but not CR. |
| Part 1: Albumin-Creatinine Ratio (ACR) at Months 6, 9, 12, 18 and 24 | Months 6, 9,12,18 and 24 | — |
| Part 1: Duration of Response | Up to 2 years | Duration of response was defined as date of 1st observation of progressive disease minus date of 1st observation of response+1 day. Duration of response was estimated by Kaplan Meier method. |
| Part 1: Time to Response | Up to 2 years | Time to response was defined as date of 1st observation of response minus date of randomization+1 day. Time to response was estimated by Kaplan Meier method. |
| Change From Baseline in eGFR Over Time | Baseline, Months 3,6,9,12,15,18, and 24 | eGFR was calculated as per the chronic kidney disease epidemiology collaboration (CKD-EPI) equation. eGFR =141×min(Scr/κ, 1)α×max(Scr κ,1)-1.209×0.993Age ×1.018\[if female\]×1.159 \[if black\] where: * Scr is serum creatinine in μmol/L, * κ is 61.9 for females and 79.6 for males, * α is -0.329 for females and -0.411 for males, min indicates the minimum of Scr/κ or 1, and max indicates the maximum of Scr/κ or 1 eGFR as a measure of kidney function. eGFR was calculated in terms of milliliter per minute per 1.73 meter square (mL/min/1.73 m\^2). A numerically smaller negative change in eGFR indicates a slowing in kidney disease progression. |
| Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE) | From the first dose until 28 days after last dose of study drug (up to 191 days) | TEAEs were defined as any AEs reported after the start of trial treatment until 28 days after the last trial treatment, defined as the treatment-emergent period. TESAEs were TEAEs that met the following criteria: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. |
| Serum Concentrations of Felzartamab Over Time | Predose and 30 minutes post-dose on Days 1, 15, 29; predose on Days 8, 57, 85, 113, 141; Post Treatment Days 169 and 267 | — |
| Percentage of Participants With Anti- Felzartamab Antibodies | From the first dose up to the end of the study (up to 2 years) | Blood samples were collected for measurement of anti-felzartamab antibodies in the serum. Number of participants with Anti-drug antibody (ADA) status positive/negative was summarized. |
Countries
Australia, Belgium, Bulgaria, Czechia, Georgia, Germany, Japan, Malaysia, Philippines, Serbia, South Korea, Spain, Taiwan, Ukraine, United States
Contacts
STUDY_DIRECTORMedical Director
HI-Bio, A Biogen Company
Participant flow
Recruitment details
Participants were enrolled at investigative sites in Belgium, Bulgaria, Czechia, Georgia, Germany, Japan, Republic of Korea, Malaysia, Philippines, Serbia, Spain, Taiwan, Ukraine, and the United States from 31 August 2021 to 06 May 2024.
Pre-assignment details
A total of 54 participants diagnosed with Immunoglobulin A Nephropathy (IgAN) were enrolled in the study, of which 48 participants completed the study. The study had 2 parts - Part 1 (Global Cohort) and Part 2 (Japanese Cohort).
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 47.4 years STANDARD_DEVIATION 10.41 |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 1 Participants |
| Race/Ethnicity, Customized Ethnicity Not Hispanic or Latino | 11 Participants |
| Race/Ethnicity, Customized Ethnicity Not Reported | 0 Participants |
| Race/Ethnicity, Customized Ethnicity Unknown | 1 Participants |
| Race/Ethnicity, Customized Race American Indian or Alaska Native | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 4 Participants |
| Race/Ethnicity, Customized Race White | 9 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 9 Participants |
| Urine Protein to Creatinine Ratio (UPCR) | 1.68 gram per gram (g/g) STANDARD_DEVIATION 0.999 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 11 | 0 / 13 | 0 / 6 |
| other Total, other adverse events | 9 / 12 | 11 / 12 | 9 / 11 | 12 / 13 | 6 / 6 |
| serious Total, serious adverse events | 1 / 12 | 1 / 12 | 1 / 11 | 0 / 13 | 0 / 6 |
Outcome results
None listed