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

Phase 3
Recruiting
Conditions
Atypical Hemolytic Uremic Syndrome
Interventions
Drug: Iptcaopan 200 mg
Registration Number
NCT05795140
Lead Sponsor
Novartis Pharmaceuticals
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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
125
Inclusion Criteria
  1. Signed informed consent must be obtained prior to participation in the open label extension study
  2. Willing and able to comply with the study Schedule of Activities
  3. 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
  4. 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
  1. Concomitant treatment with any complement inhibitor as well as concomitant treatment with any of the prohibited drugs
  2. 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
  3. Active infection or history of recurrent invasive infections caused by encapsulated bacteria such as Neisseria meningitidis, Streptococcus pneumoniae or Haemophilus influenzae
  4. History of hypersensitivity to iptacopan or its excipients or to drugs of similar chemical classes
  5. Pregnant or nursing (lactating) women
  6. 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.

Other protocol-defined inclusion/exclusion criteria may apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Iptacopan 200 mgIptcaopan 200 mgOpen label , single arm
Primary Outcome Measures
NameTimeMethod
Number of participants with adverse events and serious adverse eventsThroughout 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 ECGsThroughout 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
NameTimeMethod
Number of participants with absence of aHUS relapse without the use of anti-C5 antibodyThroughout 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 therapyThroughout 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) stageThroughout 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 statusThroughout the study duration, up to 4 years

Dialysis requirement status will be provided

Number of participants with Thrombotic Microangiopathy (TMA) related adverse eventsThroughout 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.

Trial Locations

Locations (1)

Novartis Investigative Site

🇮🇳

Pune, Maharashtra, India

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