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

• ClinicalTrials.gov Identifier: NCT05795140
• Recruitment Status: Not yet recruiting
• First Posted: April 3, 2023
• Last Update Posted: March 20, 2024
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

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

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

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 (Clinical Trial)
• Estimated 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
• Estimated Study Start Date: May 20, 2024
• Estimated Primary Completion Date: September 28, 2029
• Estimated Study Completion Date: October 9, 2029

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 Name: LNP023

Outcome Measures

Primary Outcome Measures :

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

1. Number of participants with absence of aHUS relapse without the use of anti-C5 antibody [ Time Frame: 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)
2. Number of participants with complete TMA response status without the use of anti-C5 antibody therapy [ Time Frame: 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)
3. Estimated glomerular filtration rate (eGFR) [ Time Frame: 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.

4. Chronic kidney disease (CKD) stage [ Time Frame: 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
5. Number of participants by dialysis requirement status [ Time Frame: Throughout the study duration, up to 4 years ]
   Dialysis requirement status will be provided
6. Number of participants with Thrombotic Microangiopathy (TMA) related adverse events [ Time Frame: 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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Novartis Pharmaceuticals; +41613241111; novartis.email@novartis.com

Contact: Novartis Pharmaceuticals

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05795140
• Other Study ID Numbers: CLNP023F12001B
• First Posted: April 3, 2023
• Last Update Posted: March 20, 2024
• Last Verified: March 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

aHUS; iptacopan; atypical hemolytic uremic syndrome; thrombotic microangiopathy; TMA; dialysis; CKD; eGFR; PE/PI; Complement 3 Glomerulopathy (C3G); IgAN; PNH

Additional relevant MeSH terms:

Azotemia; Hemolytic-Uremic Syndrome; Atypical Hemolytic Uremic Syndrome; Syndrome; Hemolysis; Disease; Pathologic Processes; Uremia; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia, Hemolytic; Anemia; Hematologic Diseases; Thrombotic Microangiopathies; Thrombocytopenia; Blood Platelet Disorders; Cytopenia