Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Iptacopan · 15 trials · 14 indications
UPCR is measured based on the geometric mean of 2 FMVs obtained preceding each scheduled visit.
The MG-ADL is an 8 item interviewer led patient reporting scale that assesses MG symptoms and their effects on daily activities. MG-ADL is composed of items related to patient's assessment of functional disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. Each item is assessed on a 4-points scale where a score 0 represents normal function and a score 3 represents loss of ability to perform that function. The scores ranges from 0 to 24, with a higher score indicating more disability.
Absence of thrombotic microangiopathy (TMA) manifestation, without use of anti-C5 antibody, during the 12 months of iptacopan treatment following the switch of treatment from an anti-C5 antibody to iptacopan treatment.
To demonstrate the superiority of iptacopan compared to placebo in reducing proteinuria at 6 months.
To evaluate the effect of iptacopan on proteinuria at 18 months.
To evaluate the effect of iptacopan on proteinuria at 18 months.
Change in hemoglobin (Hb) levels as mean of visits between Day 126 and Day 168 compared to baseline. Baseline is defined as as the mean of three Hb assessments conducted at the central laboratory: two during screening and the third on Day 1. The estimation of change from baseline in Hb levels was handled by the hypothetical strategy where participants were assumed as if they did not receive RBC transfusions while on treatment (RBC transfusions were expected to be rare). Assuming that participants had stable Hb levels at study entry, the mean change from baseline in Hb level between Day 126 and Day 168 was expected to be unchanged should participants have continued on anti-C5 treatment. Non-inferiority of iptacopan was therefore tested by the null hypothesis (H0) against the alternate hypothesis (H1) comparing the mean change from baseline in Hb level in iptacopan between Day 126 and Day 168 (μ) to -1 g/dL: H0: μ \<= -1, H1: μ \> -1.
The number/percentage of participants treated with iptacopan achieving complete thrombotic microangiopathy (TMA) response during 26 weeks of study treatment. Complete TMA Response is defined as (1) hematological normalization in platelet count (platelet count ≥150 x 10\^9/L) and LDH (below ULN), and (2) improvement in kidney function (≥ 25% serum creatinine reduction from baseline), maintained for two measurements obtained at least four weeks apart, and any measurement in between
Long term (one year) safety, tolerability and efficacy of iptacopan via 1) safety evaluations including adverse events/serious adverse events, safety laboratory parameters, vital signs etc. after 52 weeks of study treatment, and 2) efficacy evaluations including complete TMA response, hematological parameters (platelets, LDH, hemoglobin), eGFR, PROs after 52 weeks of study treatment
To demonstrate the superiority of iptacopan compared to placebo in reducing proteinuria at 6 months of treatment.
To evaluate the effect of iptacopan on proteinuria at 6 months.
To evaluate the effect of iptacopan on proteinuria at 12 months.
To evaluate the effect of iptacopan on proteinuria at 12 months.
Safety evaluations including but not limited to adverse events/serious adverse events, safety laboratory parameters, vital signs, etc. through End of Study visit
Sustained increase in hemoglobin levels (responder) is defined as an increase from baseline in hemoglobin levels of ≥ 2 g/dL on three out of four measurements between Day 126 and 168 of the core treatment period, without requiring red blood cell (RBC) transfusions between Day 14 and Day 168. Requiring RBC transfusions refers to any patient receiving transfusions or meeting protocol defined criteria (Hemoglobin level of ≤9 g/dL (≤8 g/dL for Chinese population) with signs and or symptoms of sufficient severity to warrant a transfusion or Hemoglobin of ≤7 g/dL (≤6 g/dL for Chinese population), regardless of presence of clinical signs and/or symptoms). The term 'marginal proportion' can be interpreted as the population average probability of being a responder. Results incorporated a method to handle missing data using multiple imputation. Hence, all 40 patients enrolled contributed to the primary analysis.
Mesangial C3c deposition is assessed by intensity of immunofluorescence (IF) staining using the following grading system: 0 (absent) 1 (+) 2 (++) 3 (+++)
To assess the effect of iptacopan in achieving sustained remission compared to standard of care (SOC)
Part 1: To evaluate the proportion of patients achieving complete renal response with iptacopan treatment "A" plus standard of care, compared to treatment alone Part 2: To evaluate the proportion of patients achieving complete renal response with Iptacopan treatment "B" plus standard of care, compared to treatment "D" alone Part 2: To evaluate the proportion of patients achieving complete renal response with Iptacopan treatment "C" plus standard of care, compared to treatment "D" alone Complete Renal Response is defined as meeting the following criteria: estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2 or no less than 85% of baseline value, and 24h urine protein-to-creatinine ratio (UPCR) ≤ 0.5 g/g.
OCT and other imaging will be performed using spectral domain OCT or swept source OCT machines
Serum LDH was used as an intravascular hemolysis marker to assess the effect of iptacopan on the reduction of chronic hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) patients when administered in addition to SoC (monoclonal antibody with anti C5 activity) Baseline is defined as the mean of the last 3 measurements prior to dose administration.
To assess the PK properties of iptacopan after a single oral dose of 200 mg in participants with mild, moderate, or severe hepatic impairment as compared to matched healthy participants with normal hepatic function (Child-Pugh classification).
To assess the PK properties of iptacopan after a single oral dose of 200 mg in participants with mild, moderate, or severe hepatic impairment as compared to matched healthy participants with normal hepatic function (Child-Pugh classification).
To assess the PK properties of iptacopan after a single oral dose of 200 mg in participants with mild, moderate, or severe hepatic impairment as compared to matched healthy participants with normal hepatic function (Child-Pugh classification).
to assess the PK properties of iptacopan after a single oral dose of 200 mg in participants with mild, moderate, or severe hepatic impairment as compared to matched healthy participants with normal hepatic function (Child-Pugh classification).
| Arm | Type | Description |
|---|---|---|
| iptacopan | EXPERIMENTAL | Participants in Cohort 1 (12 to \< 18 years old) will receive iptacopan at the dose of 200 mg twice per day. Participants in Cohort 2 (2 to \< 12 years old) will receive iptacopan at a dose tbd. |
| Matching Placebo | PLACEBO_COMPARATOR | Placebo orally for 6 months (double-blind) followed by open-label iptacopan for up to 60 months |
| iptacopan 200 mg b.i.d. | EXPERIMENTAL | open label arm of iptacopan 200 mg b.i.d. |
| iptacopan 200mg b.i.d | EXPERIMENTAL | iptacopan 200mg b.i.d |
| Placebo to iptacopan 200mg b.i.d. | PLACEBO_COMPARATOR | Placebo to iptacopan 200mg b.i.d. |
| LNP023 200mg b.i.d. | EXPERIMENTAL | Iptacopan (LNP023) at a dose of 200 mg b.i.d. orally |
| Iptacopan 200 mg b.i.d | EXPERIMENTAL | Single arm open-label with 50 adult patients receiving 200mg oral twice daily doses of iptacopan |
| iptacopan 200mg | EXPERIMENTAL | iptacopan 200 mg b.i.d. |
| Placebo to iptacopan 200mg | PLACEBO_COMPARATOR | Placebo to iptacopan 200mg b.i.d. |
| LNP023 | EXPERIMENTAL | Participants receive LNP023 at a dose of 200 mg orally b.i.d |
| Control | PLACEBO_COMPARATOR | Matching placebo |
| Iptacopan + standard of care (part 1) | ACTIVE_COMPARATOR | Iptacopan + standard of care |
| Placebo matching iptacopan + standard of care (part 1) | PLACEBO_COMPARATOR | Placebo matching iptacopan standard of care |
| Iptacopan + standard of care (part 2) | ACTIVE_COMPARATOR | Iptacopan + standard of care |
| Iptacopan + placebo (part 2) | ACTIVE_COMPARATOR | Iptacopan + placebo standard of care |
| Placebo matching iptacopan + standard of care (part 2) | ACTIVE_COMPARATOR | Placebo matching iptacopan + standard of care |
| Iptacopan (LNP023) | EXPERIMENTAL | Iptacopan (LNP023) oral use capsules |
| Placebo | PLACEBO_COMPARATOR | Placebo matched to study drug, oral use capsules |
| Cohort 1: LNP023 200mg bid + SoC | EXPERIMENTAL | Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 |
| Cohort 2: LNP023 50mg/200mg bid + SoC | EXPERIMENTAL | Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values. |
| Healthy participants | EXPERIMENTAL | Iptacopan 200 mg single dose |
| Mild hepatic impairment patients | EXPERIMENTAL | Iptacopan 200 mg single dose |
| Moderate hepatic impairment patients | EXPERIMENTAL | Iptacopan 200 mg single dose |
| Severe hepatic impairment patients | EXPERIMENTAL | Iptacopan 200 mg single dose |
| Name | Type | Description |
|---|---|---|
| iptacopan | DRUG | Cohort 1 (12 to \< 18 years of age): Iptacopan 200 mg b.i.d.(twice daily) Cohort 2 (2 to \< 12 years old): Dosing tbd |
| Matching Placebo | OTHER | Hard gelatin capsule |
| Placebo | DRUG | Placebo to iptacopan 200mg b.i.d. (Adults 200mg b.i.d; Adolescents 2x 100mg b.i.d) |
| Iptacopan (LNP023) | DRUG | Taken orally b.i.d. Dosage supplied: 200mg Dosage form: Hard gelatin capsule Route of Administration: oral |
| Rituximab | DRUG | Standard of care |
| Iptacopan (part 1) | DRUG | Taken for 52 Weeks |
| Iptacopan (part 2) | DRUG | Taken for 52 Weeks |
| Placebo + standard of care | DRUG | Taken for 52 Weeks |
| Iptacopan + placebo | DRUG | Taken for 52 Weeks |
| Standard of Care | COMBINATION_PRODUCT | Standard of Care (SoC) is defined as an antibody with anti C5 activity. At the time of study start, eculizumab was the only available SoC; eculizumab will be hereafter referred to as SoC. |
Inclusion Criteria: * Male and female participants 2 to \< 18 years of age as of Day 1. * eGFR ≥ 30 mL/min/1.73m2 where eGFR is calculated using the modified Schwartz formula at Screening and confirmed during the Run-in Period. * Kidney biopsy-proven primary IgAN\*, with biopsy performed within 3 y...