Evaluate Long-term Safety, Tolerability and Efficacy of Iptacopan in Study Participants With aHUS

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05795140

Collaborator

(none)

150

Enrollment

Arm

78.3

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This is a multicenter, single arm, open-label, extension study to evaluate the long-term safety, tolerability, and efficacy of iptacopan in participants with aHUS.

Condition or Disease	Intervention/Treatment	Phase
Atypical Hemolytic Uremic Syndrome	Drug: Iptcaopan 200 mg	Phase 3

Detailed Description

The extension study Baseline/Day 1 visit is equivalent to the End of Treatment visit of the parent study. The study will begin on Day 1 followed by on-site visits every 4 months during the study treatment period. A Safety Follow Up tele-visit must be conducted 7 days after last study treatment to collect information on Adverse Events.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

150 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multi-center, Single Arm, Open-label Extension Study to Evaluate the Long-term Safety, Tolerability and Efficacy of Iptacopan in Participants With Atypical Hemolytic Uremic Syndrome (aHUS) Who Have Completed a Preceding Iptacopan Phase 3 Study in aHUS

Anticipated Study Start Date :

Feb 12, 2024

Anticipated Primary Completion Date :

Sep 29, 2027

Anticipated Study Completion Date :

Aug 23, 2030

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Iptacopan 200 mg Open label , single arm	Drug: Iptcaopan 200 mg Open label, participant specific kits, hard gelatin capsules to be taken twice a day Other Names: LNP023

Arm

Intervention/Treatment

Experimental: Iptacopan 200 mg

Open label , single arm

Drug: Iptcaopan 200 mg

Open label, participant specific kits, hard gelatin capsules to be taken twice a day

Other Names:

LNP023

Outcome Measures

Primary Outcome Measures

Number of participants with adverse events and serious adverse events [Throughout the study duration, up to 4 years]
Number of participants with adverse events and serious adverse events will be provided
Number of participants with abnormal safety laboratory parameters, vital signs and ECGs [Throughout the study duration, up to 4 years]
Number of participants with abnormal safety laboratory parameters , vital signs and ECGs will be provided

Secondary Outcome Measures

Number of participants with absence of aHUS relapse without the use of anti-C5 antibody [Throughout the study duration, up to 4 years]
Atypical hemolytic uremic syndrome (aHUS) relapse is defined by the coexistence of at least two of the following at the same visit: thrombocytopenia (platelet count < 150 x 109 /L), microangiopathic hemolytic anemia (hemoglobin < 10 g/dl, LDH > upper limit of normal, undetectable haptoglobin, presence of schistocyte on blood smear), worsening kidney function (serum creatinine or urine protein to creatinine ratio (UPCR) > upper limit of normal and an increase of ≥ 15% compared to baseline levels)
Number of participants with complete TMA response status without the use of anti-C5 antibody therapy [Throughout the study duration, up to 4 years]
Complete thrombotic microangiopathy (TMA) Response is defined as (1) hematological normalization in platelet count (platelet count ≥150 x 109/L) and LDH (below ULN), and (2) improvement in kidney function (≥ 25% serum creatinine reduction from baseline or ≥ 25% serum creatinine reduction compared to serum creatinine values prior to initiation of anti-C5 antibody therapy)
Estimated glomerular filtration rate (eGFR) [Throughout study duration, up to 4 years]
Estimated glomerular filtration rate (eGFR) based on eGFR categories will be collected. Serum creatinine as measured in mg/dL as part of the clinical chemistry panel through the central laboratory will be used to calculate the eGFR applying the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
Chronic kidney disease (CKD) stage [Throughout study duration, up to 4 years]
Chronic kidney disease (CKD) stage (1-5) based on eGFR categories will be provided: Stage 1 (G1): Kidney damage with normal kidney function Stage 2 (G2): Mild loss of kidney function Stage 3 (G3): 3a: Mild to moderate loss of kidney function; 3b: Moderate to severe loss of kidney function Stage 4 (G4): Severe loss of kidney function Stage 5 End stage renal disease (kidney failure): Kidney failure and need for transplant or dialysis
Number of participants by dialysis requirement status [Throughout the study duration, up to 4 years]
Dialysis requirement status will be provided
Number of participants with Thrombotic Microangiopathy (TMA) related adverse events [Throughout study duration, up to 4 years]
TMA related events during the study defined as any of the following: Irreversible (>3 months) reduction in eGFR rate by ≥20%, not attributable to another cause An episode of acute kidney injury (AKI) attributed to a TMA that requires renal replacement therapy A non-renal manifestation of a TMA that requires hospitalization, or causes irreversible organ damage or death.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Signed informed consent must be obtained prior to participation in the open label extension study
Willing and able to comply with the study Schedule of Activities
Participants who have completed the full study treatment period of any prior "Novartis sponsored" iptacopan Phase 3 clinical trial in aHUS, are still on iptacopan study treatment and derive benefit from it as per Investigator's judgement
Prior vaccinations against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections should be up to date (i.e., any boosters required should be administered according to local guidelines)

Exclusion Criteria:

Concomitant treatment with any complement inhibitor as well as concomitant treatment with any of the prohibited drugs
Any comorbidity or medical condition (including but not limited to any active systemic bacterial, viral or fungal infection or malignancy) that, in the opinion of the Investigator could put the participant at risk
Active infection or history of recurrent invasive infections caused by encapsulated bacteria such as Neisseria meningitidis, Streptococcus pneumoniae or Haemophilus influenzae
History of hypersensitivity to iptacopan or its excipients or to drugs of similar chemical classes
Pregnant or nursing (lactating) women
Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of investigational drug and for 1 week after stopping of investigational drug.