IgA Nephropathy
Conditions
Keywords
glomerunephritis, complement driven, chronic kidney disease
Brief summary
Efficacy and safety of LNP023 in IgAN patients
Detailed description
This was a multicenter, randomized, double-blind, dose-ranging, parallel-group study with an adaptive design (Part 1 informed the design adaptations for Part 2). In Part 1, three doses of LNP023 (10 mg, 50 mg, and 200 mg) vs. placebo control were compared; In Part 2, four doses of LNP023 (10 mg, 50 mg, 100 mg, and 200 mg) vs. placebo control were compared. The study comprised a run-in phase in order that patients were on stable and maximally tolerated dose of Angiotensin-converting-enzyme inhibitor (ACEi) or Angiotensin II Receptor Blockers (ARB) for at least 90 days, a 90 days treatment phase in Part 1; a 180 days treatment phase in Part 2 and a 90 days follow-up phase in both Parts 1 and 2.
Interventions
DRUGLNP023
LNP023 5, 25, 100 mg capsles
OTHERPlacebo
Matching placebo to LNP023
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female and male patients above 18 years of age with a biopsy-verified IgA nephropathy and where the biopsy was performed within the prior three years. * Patients must weigh at least 35 kg to participate in the study, and must have a body mass index (BMI) within the range of 15 - 38 kg/m2. BMI = Body weight (kg) / \[Height (m)\]2 * Measured Glomerular Filtration Rate (GFR) or estimated GFR (using the CKD-EPI formula) ≥30 mL/min per 1.73 m2 * Urine protein ≥1 g/24hr at screening and ≥0.75 g / 24h after the run- in period * Vaccination against Neisseria meningitidis types A, C, Y and W-135 is required at least 30 days prior to first dosing with LNP023. Vaccination against N. meningitidis type B, S. pneumoniae and H. influenzae should be conducted if available and acceptable by local regulations, at least 30 days prior to first dosing with LNP023 * All patients must have been on supportive care including a maximally tolerated dose of ACEi or ARB therapy for the individual, antihypertensive therapy or diuretics for at least 90 days before dosing
Exclusion criteria
1. Presence of crescent formation in ≥50% of glomeruli assessed on renal biopsy 2. Patients previously treated with immunosuppressive agents such as cyclophosphamide or mycophenolate mofetil (MMF), or cyclosporine, systemic corticosteroids exposure within 90 days prior to start of LNP023/Placebo dosing 3. Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations 4. All transplanted patients (any organ, including bone marrow) 5. History of immunodeficiency diseases, or a positive HIV (ELISA and Western blot) test result. Chronic infection with Hepatitis B (HBV) or Hepatitis C (HCV). A positive HBV surface antigen (HBsAg) test, or if standard local practice, a positive HBV core antigen test, excludes a patient. Patients with a positive HCV antibody test should have HCV RNA levels measured. Subjects with positive (detectable) HCV RNA should be excluded 6. Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the study. The Investigator should make this determination in consideration of the subject's medical history and/or clinical or laboratory evidence of any of the following: * A history of invasive infections caused by encapsulated organisms, e.g. meningococcus or pneumococcus * Splenectomy * Inflammatory bowel disease, peptic ulcers, severe gastrointestinal disorder including rectal bleeding; * Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection; * Pancreatic injury or pancreatitis; * Liver disease or liver injury as indicated by abnormal liver function tests. ALT (SGPT), AST (SGOT), GGT, alkaline phosphatase and serum bilirubin will be tested. * Any single parameter of ALT, AST, GGT, alkaline phosphatase or serum bilirubin must not exceed 3 x upper limit of normal (ULN) * PT/INR must be within the reference range of normal individuals * Evidence of urinary obstruction or difficulty in voiding any urinary tract disorder other than IgNA that is associated with hematuria at screening and before dosing; \[If necessary, laboratory testing may be repeated on one occasion (as soon as possible) prior to randomization, to rule out any laboratory error\] 7. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test. 8. A history of clinically significant ECG abnormalities, or any of the following ECG abnormalities at screening or baseline: * PR \> 200 msec * QRS complex \> 120 msec * QTcF \> 450 msec (males) * QTcF \> 460 msec (females) * History of familial long QT syndrome or known family history of Torsades de Pointes * Use of agents known to prolong the QT interval unless they can be permanently discontinued for the duration of the study 9. History of severe allergic reactions as per Investigator decision 10. Plasma donation (\> 200mL) within 30 days prior to first dosing. 11. Donation or loss of 400 mL or more of blood within eight (8) weeks prior to initial dosing, or longer if required by local regulation 12. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 1 week after stopping of investigational drug. Highly effective contraception methods include: * Total abstinence from heterosexual intercourse (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. * Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking investigational drug. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. * Male sterilization (at least 6 months prior to screening). For female subjects on the study the vasectomized male partner should be the sole partner for that subject. * Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure \<1%), for example hormone vaginal ring or transdermal hormone contraception In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking investigational drug. If local regulations deviate from the contraception methods listed above and require more extensive measures to prevent pregnancy, local regulations apply and will be described in the ICF. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. 13. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in-situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases 14. History of any porphyria metabolic disorder 15. History of drug or alcohol abuse within the 12 months prior to dosing, or evidence of such abuse as indicated by the laboratory assays conducted during screening and baseline. 16. History of hypersensitivity to any of the study treatments or excipients or to drugs of similar chemical classes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MCP-Mod Estimates of the Ratio to Baseline of Urine Protein to Creatinine Ratio (UPCR) (g/Mol) - Parts 1 and 2 at Day 90 | Baseline and Day 90 | The primary analysis of the dose-response effect of LNP023 versus placebo on the reduction in UPCR 24 hours at Day 90 was done using Multiple Comparison Procedure Modelling (MCP-Mod). The existence of a dose-response relationship was assessed at the MCP step at the one-sided 10% significance level vis a multiple contrasts test. In the Mod step, the mean predicted difference between each LNP023 dose and placebo were then estimated using parametric bootstrap model averaging. Results are presented on the original scale as geometric mean ratios. A ratio less than 1 indicates a reduction in proteinuria. Participants collected all urine over a 24 hour period for UPCR test. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Estimation of the Lowest Dose Providing Maximal Reduction of Proteinuria as Measured by the Ratio to Baseline in UPCR at Day 90 | Baseline up to Month 3 | The table shows the ratio to baseline in UPCR at Day 90 by treatment group. The lowest dose providing maximal reduction of proteinuria is the dose with the smallest UPCR ratio to baseline estimate (i.e. LNP023 200mg), |
| Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Parts 1 and 2 at Day 90 | Baseline and Day 90 | eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The CKD-EPI equation is an established, widely used and Kidney Disease Improving Global Outcomes (KDIGO) guideline recommended method of GFR estimation based on serum creatinine, age, gender and race of the patient. It was derived and validated established from a meta-analyses of multiple studies including large number of patients. |
| Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Serum Creatinine - Parts 1 and 2 at Day 90 | Baseline and Day 90 | Serum creatinine |
| Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Baseline and Day 90 | Hematuria levels were the number of erythrocytes/high-power-field (hpf) measured through microscopic examination. The table shows the shift in hematuria grade (Low: \<9 rbc/hpf, Intermediate: \>=9 to \<= 50 rbc/hpf, High: \>50 rbc/hpf) from baseline (rows) to Day 90 (columns). A lower grade corresponds to a better outcome. Only patients with both baseline and Day 90 hematuria values are presented. L=low, I=intermediate and H=high in column headings for doses and BL=baseline |
| Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24hour Urine Protein (UP) - Parts 1 and 2 to Day 90 | Baseline and Day 90 | Participants collected all of their urine over a 24-hour period. |
| Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline of 24 Hour Urine Albumin (UA) - Parts 1 and 2 to Day 90 | Baseline and Day 90 | Participants collected all of their urine over a 24-hour period. |
| Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Parts 1 and 2 to Day 90 | Baseline and Day 90 | Participants collected all of their urine over a 24-hour period. |
| Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in Urine Protein to Creatinine (UPCR) From 1st Morning Void - Parts 1 and 2 at Day 90 | Baseline and Day 90 | A midstream urine sample was obtained from the first morning void (FMV) on the visit day. |
| Plasma Pharmacokinetics (PK) of Area Under the Curve at Steady State (AUCtau,ss and AUClast,ss) at Day 30 | Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs) | AUClast,ss: the area under the plasma concentration-time curve from time zero to last quantifiable concentration at steady state AUCtau,ss: the area under the plasma concentration-time curve from time zero to the end of the dosing interval tau at steady state |
| Plasma Pharmacokinetics (PK) of Pre-dose Trough at Steady State (Ctrough,ss) and Maximum Concentrations (Cmax,ss) at Day 30 | Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs) | Cmax,ss: the observed maximum plasma concentration following drug administration at steady state (ng/mL) Ctrough,ss: the pre-dose plasma concentration observed during a dosing interval at steady state (ng/mL) |
| Plasma Pharmacokinetics (PK) of Time to Maximum Concentration at Steady State (Tmax,ss) at Day 30 | Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs) | Tmax,ss: the time to reach the maximum concentration after drug administration at steady state (h) |
| Amount of LNP023 Excreted Into Urine (Ae,ss) at Day 30 | Baseline and Day 30 | Ae,ss: the total cumulative urinary excretion at steady state |
| Percent of LNP023 Excreted Into Urine at Day 30 | Baseline and Day 30 | Percent of drug excreted into the urine |
| Renal Clearance From Plasma at Steady State (CLr,ss) at Day 30 | Baseline and Day 30 | The renal clearance from plasma at steady state |
| Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Baseline, Days 8, 15, 30, 60, 90 | The complement AP biomarkers Bb and sC5b-9 were evaluated as potential pharmacodynamics and mode-of-action markers. Both biomarkers were measured using validated enzyme-linked immunosorbent assays (ELISAs). |
| Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Part 2 up to Day 180 | Baseline and Day 180 | eGFR; estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) |
| Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline Protein to Creatinine (UPCR) From 1st Morning Void - Part 2 up to Day 180 | Baseline and Day 180 | A midstream urine sample was obtained from the first morning void (FMV) on the visit day. |
| Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Baseline and Day 180 | Hematuria levels were the number of erythrocytes/high-power-field (hpf) measured through microscopic examination. The table shows the shift in hematuria grade (Low: \<9 rbc/hpf, Intermediate: \>=9 to \<= 50 rbc/hpf, High: \>50 rbc/hpf) from baseline (rows) to Day 180 (columns). A lower grade corresponds to a better outcome. Only patients with both baseline and Day 90 hematuria values are presented. L=low, I=intermediate and H=high in column headings for doses and BL=baseline |
| Mixed Model of Repeated Measures (MMRM) of the Change From Baseline in Protein Level Urine Using the Urine Protein-creatinine Ratio (UPCR) From 24 Hour Urine Collection - Part 2 up to Day 180 | Baseline, Days 30, 90 and 180 | For UPCR test, participants collected all of their urine over a 24-hour period |
| Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Part 2 up to Day 180 | Baseline and Day 180 | The 24-hour urine collection was started 1 day prior to the clinic visit, after participant urinated for the first time, than all urine was collected for the next 24 hours and refrigerated prior to clinic visit. |
Countries
Argentina, Australia, Belgium, Brazil, China, Colombia, Czechia, Denmark, Finland, France, Germany, Hong Kong, India, Israel, Japan, Malaysia, Netherlands, Norway, Singapore, South Korea, Sweden, Taiwan, Thailand, Turkey (Türkiye), United Kingdom
Participant flow
Pre-assignment details
There were 99 participants screened and 46 randomized participants completed in Part 1. There were 162 screened in Part 2 and 66 were randomized. All participants completed a run-in period of at least 30 days. Participants randomized to Part 1 could not participate in Part 2.
Participants by arm
| Arm | Count |
|---|---|
| LNP023 10 mg BID 10 mg taken twice a day | 20 |
| LNP023 50 mg BID 50 mg taken twice a day | 19 |
| LNP023 100 mg BID - Part 2 100 mg taken orally twice a day | 22 |
| LNP023 200 mg BID 200 mg taken twice a day | 26 |
| Placebo Placebo identical to LNP023 taken orally twice a day | 25 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Part 2 | Adverse Event | 0 | 1 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | LNP023 10 mg BID | LNP023 50 mg BID | LNP023 100 mg BID - Part 2 | LNP023 200 mg BID | Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 39.2 years STANDARD_DEVIATION 12.42 | 36.6 years STANDARD_DEVIATION 8.42 | 36.0 years STANDARD_DEVIATION 13.15 | 42.5 years STANDARD_DEVIATION 15.76 | 39.4 years STANDARD_DEVIATION 11 | 38.9 years STANDARD_DEVIATION 12.58 |
| Age, Customized 18 years - <65 years | 20 Participants | 19 Participants | 21 Participants | 24 Participants | 25 Participants | 109 Participants |
| Age, Customized 65 years - <85 years | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Estimated Glomerular Filtration Rate (eGFR) | 66.0 mL/min/1.73m^2 STANDARD_DEVIATION 28.51 | 53.8 mL/min/1.73m^2 STANDARD_DEVIATION 22.73 | 67.0 mL/min/1.73m^2 STANDARD_DEVIATION 31.75 | 57.9 mL/min/1.73m^2 STANDARD_DEVIATION 28.92 | 65.7 mL/min/1.73m^2 STANDARD_DEVIATION 32.6 | 62.2 mL/min/1.73m^2 STANDARD_DEVIATION 29.3 |
| Prior use of ACEi and/or ARB | 19 Participants | 19 Participants | 22 Participants | 26 Participants | 25 Participants | 111 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 10 Participants | 9 Participants | 12 Participants | 12 Participants | 11 Participants | 54 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 9 Participants | 10 Participants | 13 Participants | 13 Participants | 55 Participants |
| Sex: Female, Male Female | 11 Participants | 6 Participants | 11 Participants | 11 Participants | 7 Participants | 46 Participants |
| Sex: Female, Male Male | 9 Participants | 13 Participants | 11 Participants | 15 Participants | 18 Participants | 66 Participants |
| Supine Blood Pressure Diastolic | 84.1 mmHg STANDARD_DEVIATION 7.65 | 76.9 mmHg STANDARD_DEVIATION 8.41 | 80.0 mmHg STANDARD_DEVIATION 10.4 | 79.7 mmHg STANDARD_DEVIATION 7.62 | 78.2 mmHg STANDARD_DEVIATION 7.32 | 79.6 mmHg STANDARD_DEVIATION 8.26 |
| Supine Blood Pressure Systolic | 134.4 mmHg STANDARD_DEVIATION 11.65 | 122.6 mmHg STANDARD_DEVIATION 12.15 | 125.0 mmHg STANDARD_DEVIATION 11.3 | 125.7 mmHg STANDARD_DEVIATION 11.66 | 125.5 mmHg STANDARD_DEVIATION 11.37 | 126.5 mmHg STANDARD_DEVIATION 11.89 |
| Urine Protein to Creatinine Ratio (UPCR) | 214.1 g/mol STANDARD_DEVIATION 122.29 | 188.2 g/mol STANDARD_DEVIATION 90.38 | 203.4 g/mol STANDARD_DEVIATION 98.29 | 151.0 g/mol STANDARD_DEVIATION 109.46 | 146.6 g/mol STANDARD_DEVIATION 61.62 | 177.9 g/mol STANDARD_DEVIATION 100.02 |
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 | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 19 | 0 / 22 | 0 / 26 | 0 / 25 | 0 / 20 | 0 / 19 | 0 / 22 | 0 / 26 | 0 / 25 |
| other Total, other adverse events | 14 / 20 | 16 / 19 | 15 / 22 | 14 / 26 | 17 / 25 | 6 / 20 | 5 / 19 | 5 / 22 | 10 / 26 | 7 / 25 |
| serious Total, serious adverse events | 0 / 20 | 1 / 19 | 0 / 22 | 0 / 26 | 1 / 25 | 1 / 20 | 1 / 19 | 2 / 22 | 1 / 26 | 1 / 25 |
Outcome results
Primary
MCP-Mod Estimates of the Ratio to Baseline of Urine Protein to Creatinine Ratio (UPCR) (g/Mol) - Parts 1 and 2 at Day 90
The primary analysis of the dose-response effect of LNP023 versus placebo on the reduction in UPCR 24 hours at Day 90 was done using Multiple Comparison Procedure Modelling (MCP-Mod). The existence of a dose-response relationship was assessed at the MCP step at the one-sided 10% significance level vis a multiple contrasts test. In the Mod step, the mean predicted difference between each LNP023 dose and placebo were then estimated using parametric bootstrap model averaging. Results are presented on the original scale as geometric mean ratios. A ratio less than 1 indicates a reduction in proteinuria. Participants collected all urine over a 24 hour period for UPCR test.
Time frame: Baseline and Day 90
Population: Full analysis set - all randomized patients with a baseline and at least one post-baseline value
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LNP023 10 mg BID | MCP-Mod Estimates of the Ratio to Baseline of Urine Protein to Creatinine Ratio (UPCR) (g/Mol) - Parts 1 and 2 at Day 90 | 0.85 Ratio to baseline |
| LNP023 50 mg BID | MCP-Mod Estimates of the Ratio to Baseline of Urine Protein to Creatinine Ratio (UPCR) (g/Mol) - Parts 1 and 2 at Day 90 | 0.80 Ratio to baseline |
| LNP023 100 mg BID - Part 2 | MCP-Mod Estimates of the Ratio to Baseline of Urine Protein to Creatinine Ratio (UPCR) (g/Mol) - Parts 1 and 2 at Day 90 | 0.76 Ratio to baseline |
| LNP023 200 mg BID | MCP-Mod Estimates of the Ratio to Baseline of Urine Protein to Creatinine Ratio (UPCR) (g/Mol) - Parts 1 and 2 at Day 90 | 0.69 Ratio to baseline |
| Placebo | MCP-Mod Estimates of the Ratio to Baseline of Urine Protein to Creatinine Ratio (UPCR) (g/Mol) - Parts 1 and 2 at Day 90 | 0.88 Ratio to baseline |
p-value: 0.038Multiple Comparison Procedure-Modeling
80% CI: [0.86, 1]
80% CI: [0.76, 0.98]
80% CI: [0.72, 0.96]
80% CI: [0.66, 0.92]
Secondary
Amount of LNP023 Excreted Into Urine (Ae,ss) at Day 30
Ae,ss: the total cumulative urinary excretion at steady state
Time frame: Baseline and Day 30
Population: PK analyses set - number of participants with evaluable results for each parameter
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LNP023 10 mg BID | Amount of LNP023 Excreted Into Urine (Ae,ss) at Day 30 | 1.72 mg | Standard Deviation 1.15 |
| LNP023 50 mg BID | Amount of LNP023 Excreted Into Urine (Ae,ss) at Day 30 | 11.7 mg | Standard Deviation 5.84 |
| LNP023 100 mg BID - Part 2 | Amount of LNP023 Excreted Into Urine (Ae,ss) at Day 30 | 30.9 mg | Standard Deviation 17 |
| LNP023 200 mg BID | Amount of LNP023 Excreted Into Urine (Ae,ss) at Day 30 | 60.3 mg | Standard Deviation 27.1 |
Secondary
Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90
The complement AP biomarkers Bb and sC5b-9 were evaluated as potential pharmacodynamics and mode-of-action markers. Both biomarkers were measured using validated enzyme-linked immunosorbent assays (ELISAs).
Time frame: Baseline, Days 8, 15, 30, 60, 90
Population: Full analysis set - all randomized patients with with a baseline and at least one post-baseline value
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| LNP023 10 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 30 - Bb, n=16,17,18,26,24 | 76.4 ng/mL | Geometric Coefficient of Variation 18.32 |
| LNP023 10 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 90 sC5B-9, n=16,16,17,23,19 | 89.6 ng/mL | Geometric Coefficient of Variation 28.66 |
| LNP023 10 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 60 - Bb, n=14,16,17,25,21 | 78.8 ng/mL | Geometric Coefficient of Variation 20.26 |
| LNP023 10 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 60 sC5B-9, n=14,16,17,24,20 | 84.6 ng/mL | Geometric Coefficient of Variation 27.37 |
| LNP023 10 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 30 sC5B-9, n=16,17,18,25,24 | 85.8 ng/mL | Geometric Coefficient of Variation 23.88 |
| LNP023 10 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 15 - Bb, n=13,14,16,22,22 | 80.4 ng/mL | Geometric Coefficient of Variation 32.59 |
| LNP023 10 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 8 - Bb, n=14,16,13,25,19 | 76.7 ng/mL | Geometric Coefficient of Variation 22.89 |
| LNP023 10 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 15 sC5B-9, n=13,14,16,21,21 | 79.4 ng/mL | Geometric Coefficient of Variation 27.6 |
| LNP023 10 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 8 sC5B-9, n=12,16,13,22,17 | 80.6 ng/mL | Geometric Coefficient of Variation 12.29 |
| LNP023 10 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 90 - Bb, n=17,16,17,25,21 | 90.5 ng/mL | Geometric Coefficient of Variation 25.57 |
| LNP023 50 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 15 - Bb, n=13,14,16,22,22 | 74.1 ng/mL | Geometric Coefficient of Variation 23.3 |
| LNP023 50 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 8 - Bb, n=14,16,13,25,19 | 72.2 ng/mL | Geometric Coefficient of Variation 22.86 |
| LNP023 50 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 30 - Bb, n=16,17,18,26,24 | 76.2 ng/mL | Geometric Coefficient of Variation 23.62 |
| LNP023 50 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 60 - Bb, n=14,16,17,25,21 | 75.2 ng/mL | Geometric Coefficient of Variation 19.05 |
| LNP023 50 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 90 - Bb, n=17,16,17,25,21 | 79.3 ng/mL | Geometric Coefficient of Variation 22.47 |
| LNP023 50 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 8 sC5B-9, n=12,16,13,22,17 | 69.6 ng/mL | Geometric Coefficient of Variation 37.4 |
| LNP023 50 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 15 sC5B-9, n=13,14,16,21,21 | 72.2 ng/mL | Geometric Coefficient of Variation 33.86 |
| LNP023 50 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 30 sC5B-9, n=16,17,18,25,24 | 68.6 ng/mL | Geometric Coefficient of Variation 41.32 |
| LNP023 50 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 60 sC5B-9, n=14,16,17,24,20 | 73.7 ng/mL | Geometric Coefficient of Variation 31.99 |
| LNP023 50 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 90 sC5B-9, n=16,16,17,23,19 | 73.8 ng/mL | Geometric Coefficient of Variation 36.21 |
| LNP023 100 mg BID - Part 2 | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 8 sC5B-9, n=12,16,13,22,17 | 65.9 ng/mL | Geometric Coefficient of Variation 24.05 |
| LNP023 100 mg BID - Part 2 | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 60 sC5B-9, n=14,16,17,24,20 | 74.9 ng/mL | Geometric Coefficient of Variation 29.65 |
| LNP023 100 mg BID - Part 2 | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 30 - Bb, n=16,17,18,26,24 | 76.8 ng/mL | Geometric Coefficient of Variation 34 |
| LNP023 100 mg BID - Part 2 | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 60 - Bb, n=14,16,17,25,21 | 77.4 ng/mL | Geometric Coefficient of Variation 35.23 |
| LNP023 100 mg BID - Part 2 | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 15 - Bb, n=13,14,16,22,22 | 78.5 ng/mL | Geometric Coefficient of Variation 33.35 |
| LNP023 100 mg BID - Part 2 | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 90 - Bb, n=17,16,17,25,21 | 77.6 ng/mL | Geometric Coefficient of Variation 35.42 |
| LNP023 100 mg BID - Part 2 | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 15 sC5B-9, n=13,14,16,21,21 | 78.4 ng/mL | Geometric Coefficient of Variation 33.35 |
| LNP023 100 mg BID - Part 2 | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 8 - Bb, n=14,16,13,25,19 | 71.4 ng/mL | Geometric Coefficient of Variation 30.66 |
| LNP023 100 mg BID - Part 2 | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 90 sC5B-9, n=16,16,17,23,19 | 79.0 ng/mL | Geometric Coefficient of Variation 22.82 |
| LNP023 100 mg BID - Part 2 | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 30 sC5B-9, n=16,17,18,25,24 | 76.4 ng/mL | Geometric Coefficient of Variation 25.97 |
| LNP023 200 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 15 - Bb, n=13,14,16,22,22 | 72.9 ng/mL | Geometric Coefficient of Variation 20.47 |
| LNP023 200 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 90 sC5B-9, n=16,16,17,23,19 | 75.0 ng/mL | Geometric Coefficient of Variation 34.21 |
| LNP023 200 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 8 - Bb, n=14,16,13,25,19 | 66.3 ng/mL | Geometric Coefficient of Variation 28.15 |
| LNP023 200 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 30 - Bb, n=16,17,18,26,24 | 70.4 ng/mL | Geometric Coefficient of Variation 28.96 |
| LNP023 200 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 8 sC5B-9, n=12,16,13,22,17 | 75.8 ng/mL | Geometric Coefficient of Variation 30.15 |
| LNP023 200 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 30 sC5B-9, n=16,17,18,25,24 | 69.8 ng/mL | Geometric Coefficient of Variation 21.98 |
| LNP023 200 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 60 sC5B-9, n=14,16,17,24,20 | 76.2 ng/mL | Geometric Coefficient of Variation 29.8 |
| LNP023 200 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 15 sC5B-9, n=13,14,16,21,21 | 78.0 ng/mL | Geometric Coefficient of Variation 32.06 |
| LNP023 200 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 60 - Bb, n=14,16,17,25,21 | 72.8 ng/mL | Geometric Coefficient of Variation 23.97 |
| LNP023 200 mg BID | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 90 - Bb, n=17,16,17,25,21 | 74.6 ng/mL | Geometric Coefficient of Variation 23.91 |
| Placebo | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 60 - Bb, n=14,16,17,25,21 | 102.9 ng/mL | Geometric Coefficient of Variation 24.07 |
| Placebo | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 60 sC5B-9, n=14,16,17,24,20 | 95.7 ng/mL | Geometric Coefficient of Variation 30.11 |
| Placebo | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 90 - Bb, n=17,16,17,25,21 | 102.7 ng/mL | Geometric Coefficient of Variation 22.01 |
| Placebo | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 8 sC5B-9, n=12,16,13,22,17 | 95.2 ng/mL | Geometric Coefficient of Variation 22.01 |
| Placebo | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 90 sC5B-9, n=16,16,17,23,19 | 103.4 ng/mL | Geometric Coefficient of Variation 21.52 |
| Placebo | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 15 sC5B-9, n=13,14,16,21,21 | 99.4 ng/mL | Geometric Coefficient of Variation 25.4 |
| Placebo | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 8 - Bb, n=14,16,13,25,19 | 102.7 ng/mL | Geometric Coefficient of Variation 19.78 |
| Placebo | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 30 sC5B-9, n=16,17,18,25,24 | 94.2 ng/mL | Geometric Coefficient of Variation 24.96 |
| Placebo | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 30 - Bb, n=16,17,18,26,24 | 99.3 ng/mL | Geometric Coefficient of Variation 22.07 |
| Placebo | Change From Baseline in Plasma Levels of Circulating Fragment of Factor B (Bb) and Soluble Terminal Complement Complex (sC5b-9) Biomarkers for Parts 1 and 2 to Day 90 | Day 15 - Bb, n=13,14,16,22,22 | 108.6 ng/mL | Geometric Coefficient of Variation 23.19 |
Secondary
Estimation of the Lowest Dose Providing Maximal Reduction of Proteinuria as Measured by the Ratio to Baseline in UPCR at Day 90
The table shows the ratio to baseline in UPCR at Day 90 by treatment group. The lowest dose providing maximal reduction of proteinuria is the dose with the smallest UPCR ratio to baseline estimate (i.e. LNP023 200mg),
Time frame: Baseline up to Month 3
Population: Full analysis set - all randomized patients with a baseline and at least one post-baseline value
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LNP023 10 mg BID | Estimation of the Lowest Dose Providing Maximal Reduction of Proteinuria as Measured by the Ratio to Baseline in UPCR at Day 90 | 0.85 Ratio to baseline |
| LNP023 50 mg BID | Estimation of the Lowest Dose Providing Maximal Reduction of Proteinuria as Measured by the Ratio to Baseline in UPCR at Day 90 | 0.80 Ratio to baseline |
| LNP023 100 mg BID - Part 2 | Estimation of the Lowest Dose Providing Maximal Reduction of Proteinuria as Measured by the Ratio to Baseline in UPCR at Day 90 | 0.76 Ratio to baseline |
| LNP023 200 mg BID | Estimation of the Lowest Dose Providing Maximal Reduction of Proteinuria as Measured by the Ratio to Baseline in UPCR at Day 90 | 0.69 Ratio to baseline |
| Placebo | Estimation of the Lowest Dose Providing Maximal Reduction of Proteinuria as Measured by the Ratio to Baseline in UPCR at Day 90 | 0.88 Ratio to baseline |
Secondary
Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Part 2 up to Day 180
eGFR; estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)
Time frame: Baseline and Day 180
Population: Full analysis set 2 - all randomized patients in study Part 2 that consented to receive treatment as per protocol version 04 or higher (i.e. 180 days of treatment)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LNP023 10 mg BID | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Part 2 up to Day 180 | 0.78 mL/min/SSA | Standard Error 1.977 |
| LNP023 50 mg BID | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Part 2 up to Day 180 | -2.35 mL/min/SSA | Standard Error 1.995 |
| LNP023 100 mg BID - Part 2 | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Part 2 up to Day 180 | -2.91 mL/min/SSA | Standard Error 1.359 |
| LNP023 200 mg BID | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Part 2 up to Day 180 | -1.18 mL/min/SSA | Standard Error 1.798 |
| Placebo | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Part 2 up to Day 180 | -3.17 mL/min/SSA | Standard Error 1.868 |
80% CI: [0.42, 7.472]
80% CI: [-2.747, 4.39]
80% CI: [-2.745, 3.262]
80% CI: [-1.368, 5.337]
Secondary
Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Parts 1 and 2 at Day 90
eGFR was calculated according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). The CKD-EPI equation is an established, widely used and Kidney Disease Improving Global Outcomes (KDIGO) guideline recommended method of GFR estimation based on serum creatinine, age, gender and race of the patient. It was derived and validated established from a meta-analyses of multiple studies including large number of patients.
Time frame: Baseline and Day 90
Population: Full analysis set - all randomized patients with a baseline and at least one post-baseline value
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LNP023 10 mg BID | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Parts 1 and 2 at Day 90 | -0.06 mL/min/SSA | Standard Error 1.76 |
| LNP023 50 mg BID | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Parts 1 and 2 at Day 90 | 2.49 mL/min/SSA | Standard Error 1.859 |
| LNP023 100 mg BID - Part 2 | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Parts 1 and 2 at Day 90 | 0.23 mL/min/SSA | Standard Error 1.821 |
| LNP023 200 mg BID | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Parts 1 and 2 at Day 90 | 2.42 mL/min/SSA | Standard Error 1.545 |
| Placebo | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Estimated Glomerular Filtration Rate (eGFR) - Parts 1 and 2 at Day 90 | -3.34 mL/min/SSA | Standard Error 1.606 |
80% CI: [0.21, 6.344]
80% CI: [2.642, 9.01]
80% CI: [0.427, 6.7]
80% CI: [2.882, 8.638]
Secondary
Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Serum Creatinine - Parts 1 and 2 at Day 90
Serum creatinine
Time frame: Baseline and Day 90
Population: Full analysis set - all randomized patients with a baseline and at least one post-baseline value
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LNP023 10 mg BID | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Serum Creatinine - Parts 1 and 2 at Day 90 | -2.55 umol/L | Standard Error 3.488 |
| LNP023 50 mg BID | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Serum Creatinine - Parts 1 and 2 at Day 90 | -2.60 umol/L | Standard Error 3.665 |
| LNP023 100 mg BID - Part 2 | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Serum Creatinine - Parts 1 and 2 at Day 90 | 0.76 umol/L | Standard Error 3.555 |
| LNP023 200 mg BID | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Serum Creatinine - Parts 1 and 2 at Day 90 | -3.47 umol/L | Standard Error 3.043 |
| Placebo | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline for Serum Creatinine - Parts 1 and 2 at Day 90 | 6.65 umol/L | Standard Error 3.15 |
80% CI: [-15.253, -3.145]
80% CI: [-15.499, -3]
80% CI: [-12.04, 0.26]
80% CI: [-15.763, -4.471]
Secondary
Mixed Model of Repeated Measures (MMRM) of the Change From Baseline in Protein Level Urine Using the Urine Protein-creatinine Ratio (UPCR) From 24 Hour Urine Collection - Part 2 up to Day 180
For UPCR test, participants collected all of their urine over a 24-hour period
Time frame: Baseline, Days 30, 90 and 180
Population: Full analysis set 2 - all randomized patients in study Part 2 that consented to receive treatment as per protocol version 04 or higher (i.e. 180 days of treatment)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LNP023 10 mg BID | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline in Protein Level Urine Using the Urine Protein-creatinine Ratio (UPCR) From 24 Hour Urine Collection - Part 2 up to Day 180 | 1.06 mg/d |
| LNP023 50 mg BID | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline in Protein Level Urine Using the Urine Protein-creatinine Ratio (UPCR) From 24 Hour Urine Collection - Part 2 up to Day 180 | 0.59 mg/d |
| LNP023 100 mg BID - Part 2 | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline in Protein Level Urine Using the Urine Protein-creatinine Ratio (UPCR) From 24 Hour Urine Collection - Part 2 up to Day 180 | 0.66 mg/d |
| LNP023 200 mg BID | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline in Protein Level Urine Using the Urine Protein-creatinine Ratio (UPCR) From 24 Hour Urine Collection - Part 2 up to Day 180 | 0.73 mg/d |
| Placebo | Mixed Model of Repeated Measures (MMRM) of the Change From Baseline in Protein Level Urine Using the Urine Protein-creatinine Ratio (UPCR) From 24 Hour Urine Collection - Part 2 up to Day 180 | 0.91 mg/d |
80% CI: [0.792, 1.692]
80% CI: [0.446, 0.945]
80% CI: [0.518, 0.997]
80% CI: [0.558, 1.146]
Secondary
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Part 2 up to Day 180
The 24-hour urine collection was started 1 day prior to the clinic visit, after participant urinated for the first time, than all urine was collected for the next 24 hours and refrigerated prior to clinic visit.
Time frame: Baseline and Day 180
Population: Full analysis set 2 - all randomized patients in study Part 2 that consented to receive treatment as per protocol version 04 or higher (i.e. 180 days of treatment)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LNP023 10 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Part 2 up to Day 180 | 1.04 Ratio to baseline |
| LNP023 50 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Part 2 up to Day 180 | 0.61 Ratio to baseline |
| LNP023 100 mg BID - Part 2 | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Part 2 up to Day 180 | 0.65 Ratio to baseline |
| LNP023 200 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Part 2 up to Day 180 | 0.69 Ratio to baseline |
| Placebo | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Part 2 up to Day 180 | 0.91 Ratio to baseline |
80% CI: [0.765, 1.699]
80% CI: [0.446, 0.984]
80% CI: [0.501, 0.995]
80% CI: [0.52, 1.107]
Secondary
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Parts 1 and 2 to Day 90
Participants collected all of their urine over a 24-hour period.
Time frame: Baseline and Day 90
Population: Full analysis set - all randomized patients with a baseline and at least one post-baseline value
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LNP023 10 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Parts 1 and 2 to Day 90 | 0.85 Ratio to baseline |
| LNP023 50 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Parts 1 and 2 to Day 90 | 0.89 Ratio to baseline |
| LNP023 100 mg BID - Part 2 | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Parts 1 and 2 to Day 90 | 0.66 Ratio to baseline |
| LNP023 200 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Parts 1 and 2 to Day 90 | 0.74 Ratio to baseline |
| Placebo | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24 Hour Urine Albumin to Creatinine (UACR) - Parts 1 and 2 to Day 90 | 0.87 Ratio to baseline |
80% CI: [0.794, 1.214]
80% CI: [0.835, 1.269]
80% CI: [0.616, 0.942]
80% CI: [0.704, 1.027]
Secondary
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24hour Urine Protein (UP) - Parts 1 and 2 to Day 90
Participants collected all of their urine over a 24-hour period.
Time frame: Baseline and Day 90
Population: Full analysis set - all randomized patients with a baseline and at least one post-baseline value
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LNP023 10 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24hour Urine Protein (UP) - Parts 1 and 2 to Day 90 | 0.80 Ratio to baseline |
| LNP023 50 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24hour Urine Protein (UP) - Parts 1 and 2 to Day 90 | 0.89 Ratio to baseline |
| LNP023 100 mg BID - Part 2 | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24hour Urine Protein (UP) - Parts 1 and 2 to Day 90 | 0.61 Ratio to baseline |
| LNP023 200 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24hour Urine Protein (UP) - Parts 1 and 2 to Day 90 | 0.70 Ratio to baseline |
| Placebo | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in 24hour Urine Protein (UP) - Parts 1 and 2 to Day 90 | 0.84 Ratio to baseline |
80% CI: [0.742, 1.222]
80% CI: [0.83, 1.356]
80% CI: [0.569, 0.928]
80% CI: [0.669, 1.05]
Secondary
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in Urine Protein to Creatinine (UPCR) From 1st Morning Void - Parts 1 and 2 at Day 90
A midstream urine sample was obtained from the first morning void (FMV) on the visit day.
Time frame: Baseline and Day 90
Population: Full analysis set - all randomized patients with a baseline and at least one post-baseline value
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LNP023 10 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in Urine Protein to Creatinine (UPCR) From 1st Morning Void - Parts 1 and 2 at Day 90 | 0.76 Ratio to baseline |
| LNP023 50 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in Urine Protein to Creatinine (UPCR) From 1st Morning Void - Parts 1 and 2 at Day 90 | 0.81 Ratio to baseline |
| LNP023 100 mg BID - Part 2 | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in Urine Protein to Creatinine (UPCR) From 1st Morning Void - Parts 1 and 2 at Day 90 | 0.61 Ratio to baseline |
| LNP023 200 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in Urine Protein to Creatinine (UPCR) From 1st Morning Void - Parts 1 and 2 at Day 90 | 0.70 Ratio to baseline |
| Placebo | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline in Urine Protein to Creatinine (UPCR) From 1st Morning Void - Parts 1 and 2 at Day 90 | 0.83 Ratio to baseline |
80% CI: [0.723, 1.172]
80% CI: [0.767, 1.249]
80% CI: [0.577, 0.937]
80% CI: [0.678, 1.052]
Secondary
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline of 24 Hour Urine Albumin (UA) - Parts 1 and 2 to Day 90
Participants collected all of their urine over a 24-hour period.
Time frame: Baseline and Day 90
Population: Full analysis set - all randomized patients with a baseline and at least one post-baseline value
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LNP023 10 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline of 24 Hour Urine Albumin (UA) - Parts 1 and 2 to Day 90 | 0.79 Ratio to baseline |
| LNP023 50 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline of 24 Hour Urine Albumin (UA) - Parts 1 and 2 to Day 90 | 0.93 Ratio to baseline |
| LNP023 100 mg BID - Part 2 | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline of 24 Hour Urine Albumin (UA) - Parts 1 and 2 to Day 90 | 0.61 Ratio to baseline |
| LNP023 200 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline of 24 Hour Urine Albumin (UA) - Parts 1 and 2 to Day 90 | 0.73 Ratio to baseline |
| Placebo | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline of 24 Hour Urine Albumin (UA) - Parts 1 and 2 to Day 90 | 0.82 Ratio to baseline |
80% CI: [0.741, 1.25]
80% CI: [0.872, 1.458]
80% CI: [0.574, 0.957]
80% CI: [0.706, 1.132]
Secondary
Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline Protein to Creatinine (UPCR) From 1st Morning Void - Part 2 up to Day 180
A midstream urine sample was obtained from the first morning void (FMV) on the visit day.
Time frame: Baseline and Day 180
Population: Full analysis set 2 - all randomized patients in study Part 2 that consented to receive treatment as per protocol version 04 or higher (i.e. 180 days of treatment)
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| LNP023 10 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline Protein to Creatinine (UPCR) From 1st Morning Void - Part 2 up to Day 180 | 0.81 Ratio to baseline |
| LNP023 50 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline Protein to Creatinine (UPCR) From 1st Morning Void - Part 2 up to Day 180 | 0.72 Ratio to baseline |
| LNP023 100 mg BID - Part 2 | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline Protein to Creatinine (UPCR) From 1st Morning Void - Part 2 up to Day 180 | 0.63 Ratio to baseline |
| LNP023 200 mg BID | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline Protein to Creatinine (UPCR) From 1st Morning Void - Part 2 up to Day 180 | 0.72 Ratio to baseline |
| Placebo | Mixed Model of Repeated Measures (MMRM) of the Ratio to Baseline Protein to Creatinine (UPCR) From 1st Morning Void - Part 2 up to Day 180 | 0.79 Ratio to baseline |
80% CI: [0.68, 1.579]
80% CI: [0.607, 1.39]
80% CI: [0.558, 1.153]
80% CI: [0.614, 1.362]
Secondary
Percent of LNP023 Excreted Into Urine at Day 30
Percent of drug excreted into the urine
Time frame: Baseline and Day 30
Population: PK analyses set - number of participants with evaluable results for each parameter
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LNP023 10 mg BID | Percent of LNP023 Excreted Into Urine at Day 30 | 8.59 percent of dose | Standard Deviation 5.77 |
| LNP023 50 mg BID | Percent of LNP023 Excreted Into Urine at Day 30 | 11.7 percent of dose | Standard Deviation 5.84 |
| LNP023 100 mg BID - Part 2 | Percent of LNP023 Excreted Into Urine at Day 30 | 15.5 percent of dose | Standard Deviation 8.5 |
| LNP023 200 mg BID | Percent of LNP023 Excreted Into Urine at Day 30 | 15.1 percent of dose | Standard Deviation 6.77 |
Secondary
Plasma Pharmacokinetics (PK) of Area Under the Curve at Steady State (AUCtau,ss and AUClast,ss) at Day 30
AUClast,ss: the area under the plasma concentration-time curve from time zero to last quantifiable concentration at steady state AUCtau,ss: the area under the plasma concentration-time curve from time zero to the end of the dosing interval tau at steady state
Time frame: Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs)
Population: PK analyses set - number of participants with evaluable results for each parameter
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LNP023 10 mg BID | Plasma Pharmacokinetics (PK) of Area Under the Curve at Steady State (AUCtau,ss and AUClast,ss) at Day 30 | AUClast,ss | 5820 hr*ng/mL | Standard Deviation 1750 |
| LNP023 10 mg BID | Plasma Pharmacokinetics (PK) of Area Under the Curve at Steady State (AUCtau,ss and AUClast,ss) at Day 30 | AUCtau,ss | 8010 hr*ng/mL | Standard Deviation 2550 |
| LNP023 50 mg BID | Plasma Pharmacokinetics (PK) of Area Under the Curve at Steady State (AUCtau,ss and AUClast,ss) at Day 30 | AUCtau,ss | 17700 hr*ng/mL | Standard Deviation 4250 |
| LNP023 50 mg BID | Plasma Pharmacokinetics (PK) of Area Under the Curve at Steady State (AUCtau,ss and AUClast,ss) at Day 30 | AUClast,ss | 13000 hr*ng/mL | Standard Deviation 2740 |
| LNP023 100 mg BID - Part 2 | Plasma Pharmacokinetics (PK) of Area Under the Curve at Steady State (AUCtau,ss and AUClast,ss) at Day 30 | AUClast,ss | 18400 hr*ng/mL | Standard Deviation 6040 |
| LNP023 100 mg BID - Part 2 | Plasma Pharmacokinetics (PK) of Area Under the Curve at Steady State (AUCtau,ss and AUClast,ss) at Day 30 | AUCtau,ss | 24700 hr*ng/mL | Standard Deviation 8030 |
| LNP023 200 mg BID | Plasma Pharmacokinetics (PK) of Area Under the Curve at Steady State (AUCtau,ss and AUClast,ss) at Day 30 | AUClast,ss | 27900 hr*ng/mL | Standard Deviation 9930 |
| LNP023 200 mg BID | Plasma Pharmacokinetics (PK) of Area Under the Curve at Steady State (AUCtau,ss and AUClast,ss) at Day 30 | AUCtau,ss | 37100 hr*ng/mL | Standard Deviation 13500 |
Secondary
Plasma Pharmacokinetics (PK) of Pre-dose Trough at Steady State (Ctrough,ss) and Maximum Concentrations (Cmax,ss) at Day 30
Cmax,ss: the observed maximum plasma concentration following drug administration at steady state (ng/mL) Ctrough,ss: the pre-dose plasma concentration observed during a dosing interval at steady state (ng/mL)
Time frame: Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs)
Population: PK analyses set - number of participants with evaluable results for each parameter
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LNP023 10 mg BID | Plasma Pharmacokinetics (PK) of Pre-dose Trough at Steady State (Ctrough,ss) and Maximum Concentrations (Cmax,ss) at Day 30 | Ctrough,ss | 515 ng/mL | Standard Deviation 232 |
| LNP023 10 mg BID | Plasma Pharmacokinetics (PK) of Pre-dose Trough at Steady State (Ctrough,ss) and Maximum Concentrations (Cmax,ss) at Day 30 | Cmax,ss | 964 ng/mL | Standard Deviation 264 |
| LNP023 50 mg BID | Plasma Pharmacokinetics (PK) of Pre-dose Trough at Steady State (Ctrough,ss) and Maximum Concentrations (Cmax,ss) at Day 30 | Cmax,ss | 2150 ng/mL | Standard Deviation 480 |
| LNP023 50 mg BID | Plasma Pharmacokinetics (PK) of Pre-dose Trough at Steady State (Ctrough,ss) and Maximum Concentrations (Cmax,ss) at Day 30 | Ctrough,ss | 1130 ng/mL | Standard Deviation 348 |
| LNP023 100 mg BID - Part 2 | Plasma Pharmacokinetics (PK) of Pre-dose Trough at Steady State (Ctrough,ss) and Maximum Concentrations (Cmax,ss) at Day 30 | Ctrough,ss | 1510 ng/mL | Standard Deviation 567 |
| LNP023 100 mg BID - Part 2 | Plasma Pharmacokinetics (PK) of Pre-dose Trough at Steady State (Ctrough,ss) and Maximum Concentrations (Cmax,ss) at Day 30 | Cmax,ss | 3300 ng/mL | Standard Deviation 1080 |
| LNP023 200 mg BID | Plasma Pharmacokinetics (PK) of Pre-dose Trough at Steady State (Ctrough,ss) and Maximum Concentrations (Cmax,ss) at Day 30 | Ctrough,ss | 2200 ng/mL | Standard Deviation 964 |
| LNP023 200 mg BID | Plasma Pharmacokinetics (PK) of Pre-dose Trough at Steady State (Ctrough,ss) and Maximum Concentrations (Cmax,ss) at Day 30 | Cmax,ss | 4940 ng/mL | Standard Deviation 1770 |
Secondary
Plasma Pharmacokinetics (PK) of Time to Maximum Concentration at Steady State (Tmax,ss) at Day 30
Tmax,ss: the time to reach the maximum concentration after drug administration at steady state (h)
Time frame: Baseline (0 hr), Day 15 (0 hr) Day 30 (0, 0.25, 0.5, 1, 2, 4, 6, 8 hrs)
Population: PK analyses set - number of participants with evaluable results for each parameter
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LNP023 10 mg BID | Plasma Pharmacokinetics (PK) of Time to Maximum Concentration at Steady State (Tmax,ss) at Day 30 | 2.00 hour |
| LNP023 50 mg BID | Plasma Pharmacokinetics (PK) of Time to Maximum Concentration at Steady State (Tmax,ss) at Day 30 | 2.00 hour |
| LNP023 100 mg BID - Part 2 | Plasma Pharmacokinetics (PK) of Time to Maximum Concentration at Steady State (Tmax,ss) at Day 30 | 2.00 hour |
| LNP023 200 mg BID | Plasma Pharmacokinetics (PK) of Time to Maximum Concentration at Steady State (Tmax,ss) at Day 30 | 2.00 hour |
Secondary
Renal Clearance From Plasma at Steady State (CLr,ss) at Day 30
The renal clearance from plasma at steady state
Time frame: Baseline and Day 30
Population: PK analyses set - number of participants with evaluable results for each parameter
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| LNP023 10 mg BID | Renal Clearance From Plasma at Steady State (CLr,ss) at Day 30 | 0.112 L/hr | Standard Deviation 0.0744 |
| LNP023 50 mg BID | Renal Clearance From Plasma at Steady State (CLr,ss) at Day 30 | 0.348 L/hr | Standard Deviation 0.179 |
| LNP023 100 mg BID - Part 2 | Renal Clearance From Plasma at Steady State (CLr,ss) at Day 30 | 0.719 L/hr | Standard Deviation 0.479 |
| LNP023 200 mg BID | Renal Clearance From Plasma at Steady State (CLr,ss) at Day 30 | 0.942 L/hr | Standard Deviation 0.54 |
Secondary
Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180
Hematuria levels were the number of erythrocytes/high-power-field (hpf) measured through microscopic examination. The table shows the shift in hematuria grade (Low: \<9 rbc/hpf, Intermediate: \>=9 to \<= 50 rbc/hpf, High: \>50 rbc/hpf) from baseline (rows) to Day 180 (columns). A lower grade corresponds to a better outcome. Only patients with both baseline and Day 90 hematuria values are presented. L=low, I=intermediate and H=high in column headings for doses and BL=baseline
Time frame: Baseline and Day 180
Population: Full analysis set - all randomized patients with both baseline and Day 180 hematuria values. The number of participants analyzed corresponds to the column totals (i.e. the number of patients with non-missing baseline and Day 180 values by hematuria level at Day 180 and treatment group).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LNP023 10 mg BID | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Intermediate at baseline | 2 participants |
| LNP023 10 mg BID | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Low at baseline | 1 participants |
| LNP023 10 mg BID | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | High at baseline | 0 participants |
| LNP023 50 mg BID | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | High at baseline | 0 participants |
| LNP023 50 mg BID | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Intermediate at baseline | 1 participants |
| LNP023 50 mg BID | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Low at baseline | 1 participants |
| LNP023 200 mg BID | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Low at baseline | 5 participants |
| LNP023 200 mg BID | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Intermediate at baseline | 1 participants |
| LNP023 200 mg BID | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | High at baseline | 0 participants |
| 100mg-L | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | High at baseline | 2 participants |
| 100mg-L | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Low at baseline | 2 participants |
| 100mg-L | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Intermediate at baseline | 3 participants |
| 100mg-I | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | High at baseline | 1 participants |
| 100mg-I | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Intermediate at baseline | 0 participants |
| 100mg-I | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Low at baseline | 0 participants |
| 200mg-L | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | High at baseline | 0 participants |
| 200mg-L | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Low at baseline | 4 participants |
| 200mg-L | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Intermediate at baseline | 2 participants |
| Pl-L | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Intermediate at baseline | 0 participants |
| Pl-L | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Low at baseline | 4 participants |
| Pl-L | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | High at baseline | 0 participants |
| PL-H | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Low at baseline | 0 participants |
| PL-H | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | Intermediate at baseline | 1 participants |
| PL-H | Shift Table From Baseline for Hematuria Levels - Part 2 at Day 180 | High at baseline | 0 participants |
Secondary
Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90
Hematuria levels were the number of erythrocytes/high-power-field (hpf) measured through microscopic examination. The table shows the shift in hematuria grade (Low: \<9 rbc/hpf, Intermediate: \>=9 to \<= 50 rbc/hpf, High: \>50 rbc/hpf) from baseline (rows) to Day 90 (columns). A lower grade corresponds to a better outcome. Only patients with both baseline and Day 90 hematuria values are presented. L=low, I=intermediate and H=high in column headings for doses and BL=baseline
Time frame: Baseline and Day 90
Population: Full analysis set - all randomized patients with both baseline and Day 90 hematuria values. The number of participants analyzed corresponds to the column totals (i.e. the number of patients with non-missing baseline and day 90 values by hematuria level at Day 90 and treatment group).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| LNP023 10 mg BID | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Intermediate at baseline | 1 participants |
| LNP023 10 mg BID | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Low at baseline | 7 participants |
| LNP023 10 mg BID | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | High at baseline | 0 participants |
| LNP023 50 mg BID | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Intermediate at baseline | 3 participants |
| LNP023 50 mg BID | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | High at baseline | 0 participants |
| LNP023 50 mg BID | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Low at baseline | 1 participants |
| LNP023 200 mg BID | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | High at baseline | 0 participants |
| LNP023 200 mg BID | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Intermediate at baseline | 1 participants |
| LNP023 200 mg BID | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Low at baseline | 13 participants |
| Placebo | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Intermediate at baseline | 1 participants |
| Placebo | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Low at baseline | 0 participants |
| Placebo | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | High at baseline | 0 participants |
| 100mg-L | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | High at baseline | 2 participants |
| 100mg-L | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Low at baseline | 6 participants |
| 100mg-L | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Intermediate at baseline | 4 participants |
| 100mg-I | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Intermediate at baseline | 0 participants |
| 100mg-I | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Low at baseline | 0 participants |
| 100mg-I | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | High at baseline | 1 participants |
| 200mg-L | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Low at baseline | 6 participants |
| 200mg-L | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Intermediate at baseline | 6 participants |
| 200mg-L | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | High at baseline | 0 participants |
| 200mg-I | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Low at baseline | 0 participants |
| 200mg-I | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Intermediate at baseline | 2 participants |
| 200mg-I | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | High at baseline | 0 participants |
| Pl-L | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | High at baseline | 0 participants |
| Pl-L | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Low at baseline | 6 participants |
| Pl-L | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Intermediate at baseline | 4 participants |
| PL-I | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Low at baseline | 2 participants |
| PL-I | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | High at baseline | 0 participants |
| PL-I | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Intermediate at baseline | 0 participants |
| PL-H | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | High at baseline | 0 participants |
| PL-H | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Low at baseline | 0 participants |
| PL-H | Shift Table From Baseline for Hematuria Levels - Parts 1 and 2 at Day 90 | Intermediate at baseline | 1 participants |