Trial Outcomes & Findings for Study of Lademirsen (SAR339375) in Patients With Alport Syndrome (NCT NCT02855268)

Last Updated: 2025-09-11

Results Overview

Adverse event (AE): any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. Serious adverse event (SAE) was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs: AEs with onset after the first dose of investigational medicinal product (IMP) or existing AEs that worsened during TEAE Period (for DB Period: from first IMP administration up to first administration in OLE period for participant who entered OLE period; and up to 7 days post last IMP administration for participant not continuing OLE period; for open-label: time from 1st IMP administration in open-label to last IMP administration+ 10 weeks).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

43 participants

Primary outcome timeframe

DB: from 1st dose of IMP upto 1st dose of IMP in OLE for participant who entered OLE (Week 48); up to 7 days post last dose for participant not continuing to OLE (Week 49); OLE:1st dose of IMP (at Week 48) in OLE upto 10 weeks post last dose (Week 106)

Results posted on

2025-09-11

Participant Flow

The study was conducted at 20 active centers in 7 countries. A total of 67 participants were screened between 02 November 2019 and 30 December 2021, out of which 43 participants were randomized.

The study was planned with 2 Stages/Cohorts. Since the study was terminated early, Stage 2/Cohort 2 was not conducted. In Stage 1 analysis of double blind (DB) period performed until 48 weeks. In Stage 1 open label extension (OLE) period, only safety data was collected and assessed due to early study termination.

Participant milestones

Participant milestones
Measure	Placebo/Lademirsen Participants received subcutaneous (SC) doses of placebo (matched to lademirsen) every week (QW) during the 48 weeks of DB treatment period. Participants who received placebo and completed DB treatment period entered in OLE treatment period and received lademirsen at a dose of 110 milligrams (mg) QW for an additional 48 weeks (i.e., up to Week 96).	Lademirsen/Lademirsen Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period. Participants who completed DB treatment period entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).
DB Period (up to 48 Weeks) STARTED	14	29
DB Period (up to 48 Weeks) COMPLETED	9	19
DB Period (up to 48 Weeks) NOT COMPLETED	5	10
OLE Period (up to 96 Weeks) STARTED	9	19
OLE Period (up to 96 Weeks) COMPLETED	1	0
OLE Period (up to 96 Weeks) NOT COMPLETED	8	19

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo/Lademirsen Participants received subcutaneous (SC) doses of placebo (matched to lademirsen) every week (QW) during the 48 weeks of DB treatment period. Participants who received placebo and completed DB treatment period entered in OLE treatment period and received lademirsen at a dose of 110 milligrams (mg) QW for an additional 48 weeks (i.e., up to Week 96).	Lademirsen/Lademirsen Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period. Participants who completed DB treatment period entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).
DB Period (up to 48 Weeks) Withdrawal by Subject	1	1
DB Period (up to 48 Weeks) Adverse Event	0	2
DB Period (up to 48 Weeks) Sponsor Decision	4	7
OLE Period (up to 96 Weeks) Adverse Event	0	2
OLE Period (up to 96 Weeks) Withdrawal by Subject	1	1
OLE Period (up to 96 Weeks) Early study termination by sponsor	7	16

Baseline Characteristics

Study of Lademirsen (SAR339375) in Patients With Alport Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo/Lademirsen n=14 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period. Participants who received placebo and completed DB treatment period entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).	Lademirsen/Lademirsen n=29 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period. Participants who completed DB treatment period entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	Total n=43 Participants Total of all reporting groups
Age, Continuous	31.4 years STANDARD_DEVIATION 12.0 • n=5 Participants	34.5 years STANDARD_DEVIATION 11.5 • n=7 Participants	33.5 years STANDARD_DEVIATION 11.6 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	19 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants	8 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	7 Participants n=5 Participants	19 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
eGFR value	57.397 mL/min/1.73m^2 STANDARD_DEVIATION 16.514 • n=5 Participants	54.801 mL/min/1.73m^2 STANDARD_DEVIATION 15.726 • n=7 Participants	55.646 mL/min/1.73m^2 STANDARD_DEVIATION 15.837 • n=5 Participants

PRIMARY outcome

Timeframe: DB: from 1st dose of IMP upto 1st dose of IMP in OLE for participant who entered OLE (Week 48); up to 7 days post last dose for participant not continuing to OLE (Week 49); OLE:1st dose of IMP (at Week 48) in OLE upto 10 weeks post last dose (Week 106)

Population: Analysis was performed on safety population that included all participants who received at least one dose or partial of a dose of the IMP, analyzed according to the treatment actually received.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen n=19 Participants Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=14 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=29 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen n=9 Participants Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) TEAE	19 Participants	14 Participants	29 Participants	8 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) TESAE	1 Participants	0 Participants	2 Participants	2 Participants

PRIMARY outcome

Timeframe: Baseline, Week 48

Population: Analysis was performed on primary population that included all randomized participants who completed the double-blinded period (the first 48 weeks) or discontinued double-blinded period early.

Annualized change in eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation (for participants with age greater than 16 years) as: eGFR=142\*min(Scr/K, 1)α\*max(Scr/K, 1)\^-1.200\*0.9938\^Age\*1.012 \[if female\], where Scr = serum creatinine in milligrams per deciliter (mg/dL), K = 0.7 for females (F) and 0.9 for males (M), α = -0.241(F) and -0.302(M); age=years, calculated at time of creatinine measurement. eGFR measurements collected from baseline to Week 48 were the response variable and included fixed effects of treatment (lademirsen or placebo), screening eGFR stratification factor (less than \[\<\]60 versus greater than or equal to \[\>=\]60 milliliters per minute per 1.73 meters squared \[mL/min/1.73 m\^2\]), time, and treatment-by-time interaction. Least square (LS) mean and standard error (SE) estimated by linear mixed effect model.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=10 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=20 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Annualized Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 48	—	-4.70 mL/min/1.73 m^2/year Standard Error 2.69	-4.91 mL/min/1.73 m^2/year Standard Error 1.86	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

Population: Analysis was performed on Intent-to-Treat (ITT) population that included all randomized participants analyzed according to the treatment group allocated by randomization. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.

eGFR was used to measure level of kidney function and determine the stage of kidney disease. eGFR was calculated using CKD-EPI Creatinine Equation as: eGFR =142\*min (Scr/K, 1) α\*max (Scr/K, 1)\^-1.200\*0.9938\^Age\*1.012 \[if female\], where Scr was serum creatinine in mg/dL, K is 0.7 for females and 0.9 for males, α was -0.241 for females and -0.302 for males. Unit of age was years, calculated to reflect the age at the time when creatinine was measured.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=12 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=28 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Absolute Change From Baseline in eGFR Values at Week 24 and 48 Week 24	—	-3.43 mL/min/1.73 m^2 Standard Error 2.74	-5.15 mL/min/1.73 m^2 Standard Error 1.84	—
DB Period: Absolute Change From Baseline in eGFR Values at Week 24 and 48 Week 48	—	-7.08 mL/min/1.73 m^2 Standard Error 3.00	-6.89 mL/min/1.73 m^2 Standard Error 2.02	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

Population: Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=12 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=28 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Percent Change From Baseline in eGFR Values at Week 24 and 48 Week 24	—	-4.78 percent change Standard Error 4.51	-8.44 percent change Standard Error 3.03	—
DB Period: Percent Change From Baseline in eGFR Values at Week 24 and 48 Week 48	—	-10.05 percent change Standard Error 5.64	-12.77 percent change Standard Error 3.79	—

SECONDARY outcome

Timeframe: At Weeks 24 and 48

Population: Analysis was performed on ITT population. Here, 'number analyzed' = participants considered for the analysis for each specified category.

Estimated glomerular filtration rate was used to measure level of kidney function and determine the stage of kidney disease. eGFR was calculated using CKD-EPI Creatinine Equation as: eGFR = 142\*min(Scr/K,1)α\*max(Scr/K,1)\^-1.200\*0.9938\^Age\*1.012 \[if female\], where Scr was serum creatinine in mg/dL, K is 0.7 for females and 0.9 for males, α was -0.241 for females and -0.302 for males. Number of participants with a reduction from baseline in eGFR value of \<10%, \<20%, \<30%, or \<40% at Weeks 24 and 48 were reported in this outcome measure.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=14 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=29 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Number of Participants With a Reduction From Baseline in eGFR of <10%, <20%, <30%, or <40% at Weeks 24 and 48 <10% reduction: Week 24	—	7 Participants	16 Participants	—
DB Period: Number of Participants With a Reduction From Baseline in eGFR of <10%, <20%, <30%, or <40% at Weeks 24 and 48 <20% reduction: Week 24	—	11 Participants	23 Participants	—
DB Period: Number of Participants With a Reduction From Baseline in eGFR of <10%, <20%, <30%, or <40% at Weeks 24 and 48 <30% reduction: Week 24	—	12 Participants	26 Participants	—
DB Period: Number of Participants With a Reduction From Baseline in eGFR of <10%, <20%, <30%, or <40% at Weeks 24 and 48 <40% reduction: Week 24	—	12 Participants	26 Participants	—
DB Period: Number of Participants With a Reduction From Baseline in eGFR of <10%, <20%, <30%, or <40% at Weeks 24 and 48 <10% reduction: Week 48	—	5 Participants	8 Participants	—
DB Period: Number of Participants With a Reduction From Baseline in eGFR of <10%, <20%, <30%, or <40% at Weeks 24 and 48 <20% reduction: Week 48	—	7 Participants	13 Participants	—
DB Period: Number of Participants With a Reduction From Baseline in eGFR of <10%, <20%, <30%, or <40% at Weeks 24 and 48 <30% reduction: Week 48	—	9 Participants	14 Participants	—
DB Period: Number of Participants With a Reduction From Baseline in eGFR of <10%, <20%, <30%, or <40% at Weeks 24 and 48 <40% reduction: Week 48	—	9 Participants	16 Participants	—

SECONDARY outcome

Timeframe: From Baseline up to Week 48

Population: Analysis was performed on ITT population.

ESRD was defined as: eGFR \<=15 mL/min/1.73 m\^2; or initiation of hemodialysis; or receiving a renal transplantation during the double-blind treatment period.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=14 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=29 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Number of Participants Who Developed End Stage Renal Disease (ESRD)	—	0 Participants	1 Participants	—

SECONDARY outcome

Timeframe: From Baseline up to Week 48

Population: Analysis was performed on safety population.

Criteria for PCSA included: Hemoglobin (Hb): \<= 115 grams per liter (g/L) (Male), \<= 95 g/L (Female); greater than or equal to (\>=) 185 g/L (18.5 g/dL) (Male), \>= 165 g/L (16.5g/dL) (Female); decrease from Baseline (DFB) = 20 g/L (2g/dL); Hematocrit: \<= 0.37 volume/volume (v/v) (Male); \<= 0.32 v/v (Female); \>= 0.55 v/v (Male); \>= 0.5 v/v (Female); Red Blood Cells (RBCs):\>=6 Tera/ liter (L) and Platelets: \<100 Giga/L; \>= 700 Giga/L.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=14 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=29 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameters Hb:<=115 g/L, <=95 g/L	—	4 Participants	5 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameters Hb: >=185 g/L, >=165 g/L	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameters Hb: DFB >=20 g/L	—	1 Participants	2 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameters Hematocrit: <= 0.37 v/v; <=0.32 v/v	—	9 Participants	18 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameters Hematocrit: >=0.55 v/v; >=0.5 v/v	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameters RBCs: >=6 Tera/L	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameters Platelets: <100 Giga/L	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameters Platelets: >= 700 Giga/L	—	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: From Baseline up to Week 48

Population: Analysis was performed on safety population.

Criteria for potentially clinically significant abnormalities: Creatinine: \>=150 micromol/L (adults); \>=30% change from baseline, \>=100% change from baseline; Blood urea nitrogen: \>=17 millimoles per liter (mmol/L); Uric acid: \<120 micromol/L; \>408 micromol/L; Creatinine clearance: \<15 mL/min; \>=15 to \<30 mL/min; \>=30 to \<60 mL/min; \>=60 to \<90 mL/min; \>=90 mL/min; eGFR: \< 15 mL/min/1.73m\^2; \>=15 to \<30 mL/min/1.73m\^2; \>=30 to \<60 mL/min/1.73m\^2; \>=60 to \<90 mL/min/1.73m\^2; \>=90 mL/min. Participants might be counted more than once for specified categories.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=14 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=29 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Creatinine >=150 micromol/L	—	9 Participants	21 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Creatinine >=30%change from baseline	—	3 Participants	13 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Creatinine >=100% change from baseline	—	0 Participants	2 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Blood urea nitrogen: >=17 mmol/L	—	2 Participants	9 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Uric acid <120 micromol/L	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Uric acid >408 micromol/L	—	13 Participants	22 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Creatinine clearance <15 mL/min	—	0 Participants	1 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Creatinine clearance >=15 to <30mL/min	—	2 Participants	4 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Creatinine clearance >=30 to <60 mL/min	—	8 Participants	21 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Creatinine clearance >=60 to <90 mL/min	—	7 Participants	17 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters Creatinine clearance >=90 mL/min	—	2 Participants	5 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters eGFR <15 mL/min/1.73m^2	—	0 Participants	1 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters eGFR >=15 to <30 mL/min/1.73m^2	—	0 Participants	5 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters eGFR >=30 to <60 mL/min/1.73m^2	—	12 Participants	26 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters eGFR >=60 to <90 mL/min/1.73m^2	—	6 Participants	11 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters eGFR >=90 mL/min	—	1 Participants	3 Participants	—

SECONDARY outcome

Timeframe: From Baseline up to Week 48

Population: Analysis was performed on safety population.

Criteria for PCSA: Total bilirubin (TBILI): \>1.5 upper limit of normal (ULN); \>2 ULN; Alanine Aminotransferase (ALT): \>3 ULN; \>5 ULN; \>10 ULN; \>20 ULN; Aspartate aminotransferase (AST): \>3ULN; \>5 ULN; \>10 ULN; \>20 ULN; Alkaline phosphatase: \>1.5 ULN; ALT\>3 ULN and TBILI\>2 ULN and Direct Bilirubin\> 35% TBILI and TBILI\> 1.5 ULN.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=14 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=29 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters TBILI >1.5 ULN	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters TBILI >2 ULN	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters ALT >3 ULN	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters ALT >5 ULN	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters ALT >10 ULN	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters ALT >20 ULN	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters AST >3 ULN	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters AST >5 ULN	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters AST >10 ULN	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters AST >20 ULN	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters ALP >1.5 ULN	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters ALT >3 ULN and TBILI >2 ULN	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters Direct Bilirubin >35% TBILI and TBILI >1.5 ULN	—	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: From Baseline up to Week 48

Population: Analysis was performed on safety population.

Criteria for potentially clinically significant vital sign abnormalities: Systolic blood pressure (SBP):\<=95 mmHg and DFB \>=20 mmHg; \>=160 mmHg and increase from baseline (IFB) \>=20 mmHg; SBP (Orthostatic): \<=-20mmHg; Diastolic blood pressure (DBP): \<=45 mmHg and DFB \>=10 mmHg; \>=110 mmHg and IFB \>=10 mmHg; DBP (Orthostatic): \<=10 mmHg; heart rate (HR): \<=50 beats per minute (bpm) and DFB \>=20 bpm; \>=120 bpm and IFB\>=20 bpm and Weight: \>=5% DFB; \>=5% IFB.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=14 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=29 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs SBP <=95 mmHg and DFB >=20 mmHg	—	0 Participants	1 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs SBP >=160 mmHg and IFB >=20 mmHg	—	0 Participants	2 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs SBP (Orthostatic) <=-20mmHg	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs DBP <=45 mmHg and DFB >=10 mmHg	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs DBP >=110 mmHg and IFB >=10 mmHg	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs DBP (Orthostatic) <=-10 mmHg	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs HR <=50 bpm and DFB >=20 bpm	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs HR >=120 bpm and IFB>=20 bpm	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs Weight >=5% DFB	—	1 Participants	3 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs Weight >=5% IFB	—	4 Participants	4 Participants	—

SECONDARY outcome

Timeframe: From Baseline up to Week 48

Population: Analysis was performed on safety population.

Criteria for potentially clinically significant ECG abnormalities: HR: \<50 bpm; \<50 bpm and DFB \>=20 bpm; \<40 bpm; \<40 bpm and DFB \>=20 bpm; \<30 bpm; \<30 bpm and DFB \>=20 bpm; \>90 bpm; \>=90 bpm and IFB \>=20 bpm; \>100 bpm; \>=100bpm and IFB \>=20 bpm; \>120 bpm; \>=120 bpm and IFB \>=20 bpm; PR Interval: \>200 millisecond(ms); \>200 ms and IFB \>=25%; \>220 ms; \>220 ms and IFB \>=25%; \>240 ms; \>240 ms and IFB\>=25%; QRS Interval: \>110 ms; \>110 ms and IFB \>=25%; \>120 ms; \>120 ms and IFB \>=25%; QT Interval: \>500 ms and QTc Fridericia (QTc F): \>450 ms; \>480 ms; \>500 ms; IFB \>30 and \<=60 ms; IFB \>60 ms.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=14 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=29 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings HR <50 bpm	—	2 Participants	3 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings HR <50 bpm and DFB >=20 bpm	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings HR <40 bpm	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings HR <40 bpm and DFB >=20 bpm	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings HR <30 bpm	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings HR <30 bpm and DFB >=20 bpm	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings HR >90 bpm	—	1 Participants	1 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings HR >=90 bpm and IFB >=20 bpm	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings HR >100 bpm	—	1 Participants	1 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings HR >=100 bpm and IFB >=20 bpm	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings HR >120 bpm	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings HR >=120 bpm and IFB >=20 bpm	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings PR >200 ms	—	0 Participants	1 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings PR >200 ms and IFB >=25%	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings PR >220 ms	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings PR >220 ms and IFB >=25%	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings PR >240 ms	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings PR >240 ms and IFB>=25%	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings QRS Interval >110 ms	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings QRS Interval >110 ms and IFB >=25%	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings QRS Interval >120 ms	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings QRS Interval >120 ms and IFB >=25%	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings QT Interval >500 ms	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings QTcF >450 ms	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings QTcF >480 ms	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings QTcF >500 ms	—	0 Participants	0 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings QTcF IFB >30 and <=60 ms	—	1 Participants	4 Participants	—
DB Period: Number of Participants With Potentially Clinically Significant Abnormalities in 12-lead Electrocardiogram (ECG) Findings QTcF IFB >60 ms	—	0 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Post-dose (4 hours) on Day 1, Weeks 24 and 48

Population: Analysis was performed on PK population that included all participants who received at least one dose of IMP and had at least one post-dose PK sample. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for placebo arm.

Post-dose (4 hours) plasma concentration of lademirsen, its active major metabolite (RG0005), and SUM (lademirsen+RG0005) on Day 1, and at Weeks 24 and 48 are reported in the outcome measure. 4-hour SUM concentrations are calculated values (sum of measured lademirsen+RG0005).

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=21 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Pharmacokinetics (PK): Plasma Concentration of Lademirsen, Its Metabolite (RG0005) and SUM (Lademirsen+RG0005) Lademirsen: Day 1	—	2070 nanograms per milliliter Standard Deviation 1150	—	—
DB Period: Pharmacokinetics (PK): Plasma Concentration of Lademirsen, Its Metabolite (RG0005) and SUM (Lademirsen+RG0005) Lademirsen: Week 24	—	2180 nanograms per milliliter Standard Deviation 976	—	—
DB Period: Pharmacokinetics (PK): Plasma Concentration of Lademirsen, Its Metabolite (RG0005) and SUM (Lademirsen+RG0005) Lademirsen: Week 48	—	3080 nanograms per milliliter Standard Deviation 2170	—	—
DB Period: Pharmacokinetics (PK): Plasma Concentration of Lademirsen, Its Metabolite (RG0005) and SUM (Lademirsen+RG0005) RG0005: Day 1	—	765 nanograms per milliliter Standard Deviation 524	—	—
DB Period: Pharmacokinetics (PK): Plasma Concentration of Lademirsen, Its Metabolite (RG0005) and SUM (Lademirsen+RG0005) RG0005: Week 24	—	835 nanograms per milliliter Standard Deviation 441	—	—
DB Period: Pharmacokinetics (PK): Plasma Concentration of Lademirsen, Its Metabolite (RG0005) and SUM (Lademirsen+RG0005) RG0005: Week 48	—	876 nanograms per milliliter Standard Deviation 460	—	—
DB Period: Pharmacokinetics (PK): Plasma Concentration of Lademirsen, Its Metabolite (RG0005) and SUM (Lademirsen+RG0005) Lademirsen + RG0005: Day 1	—	2840 nanograms per milliliter Standard Deviation 1660	—	—
DB Period: Pharmacokinetics (PK): Plasma Concentration of Lademirsen, Its Metabolite (RG0005) and SUM (Lademirsen+RG0005) Lademirsen + RG0005: Week 24	—	3020 nanograms per milliliter Standard Deviation 1410	—	—
DB Period: Pharmacokinetics (PK): Plasma Concentration of Lademirsen, Its Metabolite (RG0005) and SUM (Lademirsen+RG0005) Lademirsen + RG0005: Week 48	—	3960 nanograms per milliliter Standard Deviation 2350	—	—

SECONDARY outcome

Timeframe: Pre-dose (up to 4 hours before study drug administration) on Weeks 4, 12, 24, 36 and 48

Population: Analysis was performed on PK population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category. Data for this outcome measure was not planned to be collected and analyzed for placebo arm.

Ctrough was measured from the pre-dose (up to 4 hours before study drug administration) plasma samples collected at Weeks 4, 12, 24, 36 and 48. SUM concentrations (lademirsen+RG0005) are measured values (assay measures lademirsen+ RG0005).

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=13 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Pharmacokinetics: Trough Plasma Concentrations (Ctrough) of SUM (Lademirsen+RG0005) Week 36	—	18.6 nanograms per milliliter Standard Deviation 8.18	—	—
DB Period: Pharmacokinetics: Trough Plasma Concentrations (Ctrough) of SUM (Lademirsen+RG0005) Week 4	—	7.65 nanograms per milliliter Standard Deviation 3.36	—	—
DB Period: Pharmacokinetics: Trough Plasma Concentrations (Ctrough) of SUM (Lademirsen+RG0005) Week 12	—	12.6 nanograms per milliliter Standard Deviation 7.05	—	—
DB Period: Pharmacokinetics: Trough Plasma Concentrations (Ctrough) of SUM (Lademirsen+RG0005) Week 24	—	15.1 nanograms per milliliter Standard Deviation 8.65	—	—
DB Period: Pharmacokinetics: Trough Plasma Concentrations (Ctrough) of SUM (Lademirsen+RG0005) Week 48	—	19.5 nanograms per milliliter Standard Deviation 10.2	—	—

SECONDARY outcome

Timeframe: From first IMP administration (Day 1) up to first administration in OLE period for participant who entered OLE period (i.e., up to W48) & up to 7 days post last IMP administration for participant not continuing OLE period (i.e., up to W49)

Population: Analysis was performed on ADA population that included all randomized participants who received at least one dose of study drugs and had at least one post-baseline ADA sample.

ADA responses were categorized as: treatment-induced, and treatment-boosted response. Participant whose ADA status was negative at baseline but positive (ADA titer value \>=50) anytime post-baseline or missing at baseline was considered to have treatment-induced ADA. Participant whose ADA status was positive at baseline (pre-existing ADA) and the ADA titer level anytime post-baseline was significantly higher (\>= twice the minimum required dilution) than that at baseline was considered to have treatment-boosted ADA.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=11 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=22 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Number of Participants With Treatment-emergent Anti-drug Antibodies (ADAs) Response Treatment-induced ADAs	—	0 Participants	6 Participants	—
DB Period: Number of Participants With Treatment-emergent Anti-drug Antibodies (ADAs) Response Treatment-boosted ADAs	—	0 Participants	0 Participants	—

SECONDARY outcome

Population: Analysis was performed on ADA population. For this outcome measure analysis was done separately for TE-ADA positive and negative participants for placebo and lademirsen arms respectively. Here, "0" in the "overall number of participants analyzed" signifies that no participants had ADA positive response in the placebo arm.

TEAEs: AE developed/worsened/became serious during TEAE period (from first IMP administration in DB period to first administration in OLE period for those who entered OLE (i.e., up to W48), up to 7 days post last dose for those not continuing to OLE period (i.e., up to W49). TESAEs: any untoward medical occurrence that resulted in death, was life-threatening, required inpatient hospitalization/prolongation of hospitalization, resulted in persistent/significant disability, was a congenital anomaly/birth defect, or a medically important event. ADA response was categorized as treatment-induced (participant whose ADA status was positive \[ADA titer value \>=50\] anytime post-baseline and was negative/missing at baseline), treatment-boosted (participant whose ADA status was positive at baseline \& ADA titer level anytime post-baseline was significantly higher). In this outcome measure, number of participants with TEAEs as per ADA responses (positive or negative) were reported.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen n=16 Participants Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=11 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen n=6 Participants Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Associated With Anti-drug Antibody (ADA) Responses TEAEs	16 Participants	—	11 Participants	6 Participants
DB Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs) Associated With Anti-drug Antibody (ADA) Responses TESAEs	1 Participants	—	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

Population: Data for this outcome measure could not be analyzed and reported as the samples for circulating microRNA-21 at the predefined timepoints, Weeks 24 and 48 were not collected and analyzed due to early study termination.

Circulating microRNA-21 were the supportive biomarkers assessed in study.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

BUN was the supportive biomarker assessed during the study. Change from Baseline in BUN at Weeks 24 and 48 was reported in this outcome measure.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=12 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=28 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Change From Baseline in Blood Urea Nitrogen (BUN) Values at Weeks 24 and 48 Week 24	—	-0.89 milligrams per deciliter (mg/dL) Standard Deviation 5.96	2.54 milligrams per deciliter (mg/dL) Standard Deviation 8.07	—
DB Period: Change From Baseline in Blood Urea Nitrogen (BUN) Values at Weeks 24 and 48 Week 48	—	-1.54 milligrams per deciliter (mg/dL) Standard Deviation 7.23	5.80 milligrams per deciliter (mg/dL) Standard Deviation 6.09	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

Urine protein and creatinine were the supportive biomarker assessed during the study. Change from Baseline in urine protein to creatinine ratio at Weeks 24 and 48 was reported in this outcome measure.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=11 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=22 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Change From Baseline in Urine Protein/Creatinine Ratio at Weeks 24 and 48 Week 24	—	-0.085 ratio Standard Deviation 1.680	0.438 ratio Standard Deviation 1.451	—
DB Period: Change From Baseline in Urine Protein/Creatinine Ratio at Weeks 24 and 48 Week 48	—	0.300 ratio Standard Deviation 2.308	0.745 ratio Standard Deviation 1.149	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

Urine albumin and creatinine were the supportive biomarker assessed during the study. Change from Baseline in urine albumin to creatinine ratio at Weeks 24 and 48 was reported in this outcome measure.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=11 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=24 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Change From Baseline in Urine Albumin/Creatinine Ratio at Weeks 24 and 48 Week 24	—	11.65 ratio Standard Deviation 1436.63	271.28 ratio Standard Deviation 1066.40	—
DB Period: Change From Baseline in Urine Albumin/Creatinine Ratio at Weeks 24 and 48 Week 48	—	206.01 ratio Standard Deviation 1585.93	447.54 ratio Standard Deviation 863.94	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

EGF and creatinine were the supportive biomarker assessed during the study. Change from Baseline in urine EGF to creatinine ratio at Weeks 24 and 48 was reported in this outcome measure.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=6 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=19 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Change From Baseline in Urine Epidermal Growth Factor (EGF)/Creatinine Ratio at Weeks 24 and 48 Week 24	—	-5.03 ratio Standard Deviation 5.42	1.84 ratio Standard Deviation 7.28	—
DB Period: Change From Baseline in Urine Epidermal Growth Factor (EGF)/Creatinine Ratio at Weeks 24 and 48 Week 48	—	-5.48 ratio Standard Deviation 7.04	0.37 ratio Standard Deviation 2.00	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

Creatinine was the supportive biomarker assessed during the study. Change from Baseline in blood creatinine values at Weeks 24 and 48 was reported in this outcome measure.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=12 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=28 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Change From Baseline in Blood Creatinine Values at Weeks 24 and 48 Week 24	—	0.082 mg/dL Standard Deviation 0.201	0.173 mg/dL Standard Deviation 0.354	—
DB Period: Change From Baseline in Blood Creatinine Values at Weeks 24 and 48 Week 48	—	0.119 mg/dL Standard Deviation 0.186	0.201 mg/dL Standard Deviation 0.403	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

Creatinine was the supportive biomarker assessed during the study. Change from Baseline in urine creatinine values at Weeks 24 and 48 was reported in this outcome measure.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=12 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=27 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Change From Baseline in Urine Creatinine Values at Weeks 24 and 48 Week 24	—	-0.319 mg/dL Standard Deviation 62.960	-3.595 mg/dL Standard Deviation 38.344	—
DB Period: Change From Baseline in Urine Creatinine Values at Weeks 24 and 48 Week 48	—	-16.461 mg/dL Standard Deviation 55.160	-24.880 mg/dL Standard Deviation 30.789	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

Cystatine C was the supportive biomarker assessed during the study. Change from Baseline in blood cystatine C values at Weeks 24 and 48 was reported in this outcome measure.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=12 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=28 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Change From Baseline in Blood Cystatine C Values at Weeks 24 and 48 Week 24	—	0.061 mg/dL Standard Deviation 0.191	0.159 mg/dL Standard Deviation 0.269	—
DB Period: Change From Baseline in Blood Cystatine C Values at Weeks 24 and 48 Week 48	—	0.147 mg/dL Standard Deviation 0.258	0.282 mg/dL Standard Deviation 0.387	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

Cystatin C and Creatinine were the supportive biomarker assessed during the study. Change from Baseline in urine cystatin C to creatinine ratio at Weeks 24 and 48 was reported in this outcome measure.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=4 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=15 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Change From Baseline in Urine Cystatin C/Creatinine Ratio at Weeks 24 and 48 Week 24	—	35.203 ratio Standard Deviation 146.405	201.681 ratio Standard Deviation 1030.016	—
DB Period: Change From Baseline in Urine Cystatin C/Creatinine Ratio at Weeks 24 and 48 Week 48	—	81.309 ratio Standard Deviation 106.162	41.290 ratio Standard Deviation 194.150	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

Transforming growth factor beta 1 was the supportive biomarker assessed during the study. Change from Baseline in blood transforming growth factor beta 1 values at Week 24 and 48 was reported in this outcome measure.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=5 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=15 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Change From Baseline in Blood Transforming Growth Factor Beta 1 Values at Week 24 and 48 Week 24	—	15.66 nanograms per milliliter (ng/mL) Standard Deviation 19.59	0.06 nanograms per milliliter (ng/mL) Standard Deviation 21.46	—
DB Period: Change From Baseline in Blood Transforming Growth Factor Beta 1 Values at Week 24 and 48 Week 48	—	-5.87 nanograms per milliliter (ng/mL) Standard Deviation 13.76	0.89 nanograms per milliliter (ng/mL) Standard Deviation 15.08	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

Transforming growth factor beta 1 and creatinine were the supportive biomarker assessed during the study. Change from Baseline in urine transforming growth factor beta 1 to creatinine ratio at Week 24 and 48 was reported in this outcome measure.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=6 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=19 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Change From Baseline in Urine Transforming Growth Factor Beta 1/Creatinine Ratio at Week 24 and 48 Week 24	—	6031.03 ratio Standard Deviation 13412.10	1088.87 ratio Standard Deviation 4990.98	—
DB Period: Change From Baseline in Urine Transforming Growth Factor Beta 1/Creatinine Ratio at Week 24 and 48 Week 48	—	-636.16 ratio Standard Deviation 2864.99	1268.16 ratio Standard Deviation 6000.78	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

Blood Lipocalin-2 was the supportive biomarker assessed during the study. Change from Baseline in blood lipocalin-2 at Weeks 24 and 48 was reported in this outcome measure.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=12 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=28 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Change From Baseline in Blood Lipocalin-2 Values at Weeks 24 and 48 Week 24	—	6.3989 micrograms per liter (mcg/L) Standard Deviation 38.2043	14.9748 micrograms per liter (mcg/L) Standard Deviation 62.3959	—
DB Period: Change From Baseline in Blood Lipocalin-2 Values at Weeks 24 and 48 Week 48	—	25.5433 micrograms per liter (mcg/L) Standard Deviation 32.6328	31.0391 micrograms per liter (mcg/L) Standard Deviation 41.2171	—

SECONDARY outcome

Timeframe: Baseline, Weeks 24 and 48

Lipocalin-2 and Creatinine were the supportive biomarker assessed during the study. Change from Baseline in urine lipocalin-2 to creatinine ratio at Weeks 24 and 48 was reported in this outcome measure.

Outcome measures

Outcome measures
Measure	OLE Period: Lademirsen/Lademirsen Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).	DB Period: Placebo n=10 Participants Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=26 Participants Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).
DB Period: Change From Baseline in Urine Lipocalin-2/Creatinine Ratio at Weeks 24 and 48 Week 24	—	-14.7119 ratio Standard Deviation 25.6736	16.7727 ratio Standard Deviation 173.1358	—
DB Period: Change From Baseline in Urine Lipocalin-2/Creatinine Ratio at Weeks 24 and 48 Week 48	—	65.9768 ratio Standard Deviation 107.4255	47.5224 ratio Standard Deviation 101.1673	—

Adverse Events

DB Period: Placebo

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

DB Period: Lademirsen

Serious events: 2 serious events

Other events: 29 other events

Deaths: 0 deaths

OLE Period: Placebo/Lademirsen

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

OLE Period: Lademirsen/Lademirsen

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	DB Period: Placebo n=14 participants at risk Participants received SC doses of placebo (matched to lademirsen) QW during the 48 weeks of DB treatment period.	DB Period: Lademirsen n=29 participants at risk Participants received SC doses of lademirsen 110 mg QW during the 48 weeks of DB treatment period.	OLE Period: Placebo/Lademirsen n=9 participants at risk Participants who completed DB treatment period with placebo (matched to lademirsen) QW, entered in OLE treatment period and received lademirsen at a dose of 110 mg QW for an additional 48 weeks (i.e., up to Week 96).	OLE Period: Lademirsen/Lademirsen n=19 participants at risk Participants who completed DB treatment period with lademirsen 110 mg QW, entered in OLE treatment period and continued the same lademirsen treatment in OLE period for an additional 48 weeks (i.e., up to Week 96).
Infections and infestations Respiratory Tract Infection	0.00% 0/14 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.	3.4% 1/29 • Number of events 1 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.	0.00% 0/9 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.	0.00% 0/19 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.
Nervous system disorders Complex Regional Pain Syndrome	0.00% 0/14 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.	0.00% 0/29 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.	11.1% 1/9 • Number of events 1 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.	0.00% 0/19 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.
Investigations Blood Creatinine Increased	0.00% 0/14 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.	0.00% 0/29 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.	11.1% 1/9 • Number of events 1 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.	0.00% 0/19 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.
Investigations Glomerular Filtration Rate Decreased	0.00% 0/14 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.	3.4% 1/29 • Number of events 1 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.	11.1% 1/9 • Number of events 1 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.	5.3% 1/19 • Number of events 1 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.
Injury, poisoning and procedural complications Hand Fracture	0.00% 0/14 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.	0.00% 0/29 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.	11.1% 1/9 • Number of events 1 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.	0.00% 0/19 • DB period: First IMP administration in DB period up to first IMP administration in OLE period for participant who entered OLE period (i.e., up to Week 48); and up to 7 days post last IMP administration for participant who didn't enter OLE period (i.e., up to Week 49). OLE period: first IMP administration (at Week 48) in OLE period upto 10 weeks post last IMP administration (i.e., up to Week 106) Analysis was performed on safety population.

Other adverse events

Additional Information

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