Randomized, placebo-controlled, multi-center, double-blind, proof of concept phase IIa trial and dose evaluation trial of felzartamab in IgAN
Study Sponsor, originally HI-Bio, Inc., is now HI-Bio, A Biogen Company.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
54
anti-CD38+ monoclonal antibody
Placebo comparator
Part 1: Relative Change From Baseline in Urine Protein to Creatinine Ratio (UPCR) in 24-hour Urine at 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.
Time frame: Baseline, Month 9
Integrative Analysis of Several Endpoints: Percent Change From Baseline in Immunoglobulin A (IgA) Concentration by Predose Serum Concentration (Ctrough) Group
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.
Time frame: Up to 9 months
Integrative Analysis of Several Endpoints: Maximum Serum Concentrations (Cmax) as Per the Infusion-Related Reactions (IRRs) After the First Dose
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.
Time frame: Up to 1 week
Part 1: Relative Change From Baseline in UPCR in 24-hour Urine at 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.
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FOMAT Medical Research - FOMAT - HyperCore - PPDS
Oxnard, California, United States
Amicis Research Center, Vacaville
Vacaville, California, United States
Mayo Clinic Hospital - Methodist Campus
Rochester, Minnesota, United States
MedResearch INC
El Paso, Texas, United States
Core Research Group
Milton, Queensland, Australia
Sunshine Hospital - Australia
Saint Albans, Victoria, Australia
Imelda VZW
Bonheiden, Antwerpen, Belgium
UZ Leuven Hospital
Leuven, Vlaams Brabant, Belgium
Regionaal Ziekenhuis Jan Yperman VZW
Ieper, Belgium
CHU Sart Tilman Hospital
Liège, Belgium
...and 49 more locations
Time frame: Baseline, Months 3,6,12,18 and 24
Part 1: Number of Participants With Complete Response (CR) at 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).
Time frame: Months 3,6,9,12,18 and 24
Part 1: Percentage of Participants With Response at 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.
Time frame: Months 3,6,9,12,18 and 24
Part 1: Albumin-Creatinine Ratio (ACR) at Months 6, 9, 12, 18 and 24
Time frame: Months 6, 9,12,18 and 24
Part 1: Duration of Response
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.
Time frame: Up to 2 years
Part 1: Time to Response
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.
Time frame: Up to 2 years
Change From Baseline in eGFR Over Time
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.
Time frame: Baseline, Months 3,6,9,12,15,18, and 24
Number of Participants With Treatment Emergent Adverse Event (TEAE) and Treatment Emergent Serious Adverse Event (TESAE)
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.
Time frame: From the first dose until 28 days after last dose of study drug (up to 191 days)
Serum Concentrations of Felzartamab Over Time
Time frame: 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
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.
Time frame: From the first dose up to the end of the study (up to 2 years)