IPTACOPAN for Atypical hemolytic uremic syndrome

Inclusion criteria

• {"criterion_text":"- Signed informed consent must be obtained prior to participation in the study"}
• {"criterion_text":"- Male and female participants ≥ 18 years of age at the time of consent."}
• {"criterion_text":"- Willing and able to comply with the study visit schedule"}
• {"criterion_text":"- Participants with diagnosis of aHUS for whom etiologies of other types of TMA (eg., Thrombotic Thrombocytopenic Purpura (TTP), Shiga Toxin producing Escherichia Coli (STEC)-TMA, Pneumococcal hemolytic uremic syndrome, TMA secondary to cobalamin C defect, TMA related to Diacylglycerol kinase ε (DGKE) nephropathy) and non-aHUS kidney disease have been excluded."}
• {"criterion_text":"- Currently on the recommended (as per label) dosage regimen of anti-C5 antibody treatment (eg., eculizumab or ravulizumab), for at least 3 months prior to entering the screening period ."}
• {"criterion_text":"- In the opinion of the investigator the participant has responded to anti-C5 antibody treatment prior to screening and has clinical evidence of response (in absence of PE/PI) during the Screening period. Clinical evidence of response to anti-C5 antibody treatment (in absence of PE/PI) confirmed during the Screening period by central laboratory at two visits 12 weeks apart. Clinical evidence of response is defined as: •\tHematological normalization in platelet count ≥150 x 109/L and LDH below upper limit of normal [ULN], and Stable kidney function as defined by serum creatinine values within ±15% during the Screening period ."}
• {"criterion_text":"- Vaccination against Neisseria meningitidis and Streptococcus pneumoniae infections is required prior to the start of treatment with iptacopan. If the participant has not been previously vaccinated or if a booster is required, the vaccine(s) should be given, according to local regulations, at least 2 weeks prior to first iptacopan dosing. If iptacopan treatment has to start earlier than 2 weeks post-vaccination, prophylactic antibiotic treatment must be initiated at the start of iptacopan study treatment and for at least 2 weeks after vaccination"}
• {"criterion_text":"- If not received previously or if a booster is required, vaccination against Haemophilus influenzae infection, should be given, if available and according to local regulations, at least 2 weeks prior to first iptacopan dosing."}

Exclusion criteria

• {"criterion_text":"- History of aHUS disease relapse while on anti-C5 antibody treatment."}
• {"criterion_text":"- Uncontrolled arterial hypertension (systolic blood pressure >160 mmHg)."}
• {"criterion_text":"- Active infection or history of recurrent invasive infections caused by encapsulated bacteria, i.e. meningococcus, pneumococcus (eg., N. meningitidis, S. pneumoniae) or H. influenzae."}
• {"criterion_text":"- Participants with sepsis or active systemic bacterial, viral (including COVID-19) or fungal infection within 14 days prior to study treatment administration."}
• {"criterion_text":"- Human immunodeficiency virus (HIV) infection (known history of HIV or test positive for HIV at screening)."}
• {"criterion_text":"- Kidney, bone marrow transplant (BMT)/hematopoietic stem cell transplant (HSCT), heart, lung, small bowel, pancreas, liver transplantation or any other cell or solid organ transplantation."}
• {"criterion_text":"- History of drug or alcohol abuse within the 12 months prior to dosing."}
• {"criterion_text":"- Women of child-bearing potential (WCBP), defined as all women physiologically capable of becoming pregnant from menarche until becoming post-menopausal, unless they are using effective methods of contraception during dosing of iptacopan and for 1 week after stopping of iptacopan. Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., hormonal profile confirming menopause and/or age-appropriate history of vasomotor symptoms)."}
• {"criterion_text":"- Participants committed to an institution by virtue of an order issued either by the judicial or the administrative authorities"}
• {"criterion_text":"- Participants dependent on the sponsor, the study site or the Investigator"}
• {"criterion_text":"- Liver disease, such as active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection defined as hepatitis B virus surface antibody (HBsAg) positive or HCV RNA positive, or liver injury as indicated by abnormal liver function tests at Screening as defined below: •\tAny single parameter of alanine amino transferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase must not exceed 3×upper limit of normal (ULN)."}
• {"criterion_text":"- Any medical condition deemed likely to interfere with the participant’s participation in the study."}
• {"criterion_text":"- Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations."}
• {"criterion_text":"- History of hypersensitivity to iptacopan or any of its excipients or to drugs of similar chemical classes."}
• {"criterion_text":"- History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer) treated or untreated within the past 5 years, regardless of whether there is evidence of local recurrence or metastases"}
• {"criterion_text":"- Female participants who are pregnant or breastfeeding, or intending to conceive during the course of the study."}
• {"criterion_text":"- Women of child-bearing potential (WCBP), defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of iptacopan and for 1 week after stopping of iptacopan."}
• {"criterion_text":"- eGFR < 30 ml/min/1.73m2."}

Primary endpoints

• {"endpoint_text":"- Absence of TMA manifestation without use of anti-C5 antibody (for TMA manifestation) during 12 months of iptacopan treatment following the switch of treatment from an anti-C5 antibody to iptacopan treatment.","definition_or_measurement_approach":"Measured as absence of TMA manifestation and no use of anti-C5 antibody over 12 months of iptacopan treatment following the switch; assessed over the 12-month treatment period."}

Secondary endpoints

• {"endpoint_text":"- Absence of TMA manifestation without the use of anti-C5 antibody (for TMA manifestation) during 12 months of iptacopan treatment following the switch of treatment from an anti-C5 antibody to iptacopan treatment.","definition_or_measurement_approach":"Same as primary: absence of TMA manifestation and no use of anti-C5 antibody during 12 months of iptacopan treatment."}
• {"endpoint_text":"- Time to TMA manifestation during 12 Months of iptacopan treatment","definition_or_measurement_approach":"Time-to-event measurement: time from switch to first TMA manifestation within 12 months of iptacopan treatment."}
• {"endpoint_text":"- Change from baseline in hematologic parameters (platelets, LDH, hemoglobin) and kidney function (serum creatinine, UPCR, eGFR, CKD stage) at Month 12 of iptacopan treatment.","definition_or_measurement_approach":"Change from baseline to Month 12 in specified laboratory and renal function parameters."}
• {"endpoint_text":"- Dialysis requirement status (YES/NO) through 12 months of iptacopan treatment","definition_or_measurement_approach":"Binary assessment (YES/NO) of dialysis requirement status during the 12-month treatment period."}
• {"endpoint_text":"- Safety evaluations during 12 months of iptacopan treatment (including adverse events/serious adverse events, safety laboratory parameters and vital signs)","definition_or_measurement_approach":"Safety assessments including recording of AEs/SAEs, laboratory safety parameters and vital signs over 12 months."}
• {"endpoint_text":"- TMA related events during 12 months of iptacopan treatment. TMA related events are defined as any of the following: •\tIrreversible (>3 months) reduction in estimated glomerular filtration rate (eGFR) by ≥20%, not attributable to another cause •\tAn episode of acute kidney injury (AKI) attributed to a TMA that requires renal replacement therapy •\tA non-renal manifestation of a TMA that requires hospitalization, or causes irreversible organ damage or death.","definition_or_measurement_approach":"TMA related events defined explicitly as: irreversible ≥20% eGFR reduction (>3 months) not attributable to other cause; AKI attributed to TMA requiring renal replacement therapy; non-renal TMA manifestations requiring hospitalization or causing irreversible organ damage or death; assessed during 12 months."}

Methods

• Study-related materials (posters, flyers) and patient recruitment/retention materials provided by Publicis Healthcare Communications Group Limited (United Kingdom); country-specific recruitment arrangements documented (recruitment arrangements documents exist per country).

Italy

Earliest CTIS Part Ii Submission Date

18-12-2023

Latest Decision Or Authorization Date

14-01-2026

Processing Time Days

758

Number Of Sites

3

Number Of Participants

4

Spain

Earliest CTIS Part Ii Submission Date

19-12-2023

Latest Decision Or Authorization Date

13-01-2026

Processing Time Days

756

Number Of Sites

6

Number Of Participants

6

Germany

Earliest CTIS Part Ii Submission Date

20-12-2023

Latest Decision Or Authorization Date

15-01-2026

Processing Time Days

757

Number Of Sites

2

Number Of Participants

4

France

Earliest CTIS Part Ii Submission Date

29-01-2024

Latest Decision Or Authorization Date

16-01-2026

Processing Time Days

718

Number Of Sites

8

Number Of Participants

14

Primary sponsor

Full Name

Novartis Pharma AG

Organisation Type

Pharmaceutical company

Country Of Registered Address

Switzerland

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

SAP, TFL shells, SDTMs, ADaMs, TFLs and defins.xmls.

Name

IQVIA Limited

Responsibilities

Randomization Management of drug supply logistics and dispensing

Name

Parexel International (IRL) Limited

Responsibilities

Clinical trial support (code 12) as listed

Name

Syneos Health Inc.

Responsibilities

Provided services (code 1) - responsibilities listed in sponsor third parties

Third parties

• {"country":"United Kingdom","full_name":"Publicis Healthcare Communications Group Limited","duties_or_roles":"Provide study related materials (print/digital) i.e posters, flyers, Patient recruitment/retention","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Medical Equipment Supplies And Management Limited","duties_or_roles":"Ancillary Supplies","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Somalogic Operating Co. Inc.","duties_or_roles":"Protein profiling in serum, urine, saliva as applicable","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"RWS Life Sciences Inc.","duties_or_roles":"PRO formatting, translations and licensing","organisation_type":"Pharmaceutical company"}
• {"country":"France","full_name":"SGS France","duties_or_roles":"Analysis blood biomarkers","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Adelphi Values Limited","duties_or_roles":"Provider of Patient Experience Interview","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"SAP, TFL shells, SDTMs, ADaMs, TFLs and defins.xmls.","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"Eurofins Genomics Europe Genotyping A/S","duties_or_roles":"DNA Analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"EPL Pathology Archives LLC","duties_or_roles":"Biomarkers Aliquoting.","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Italy","full_name":"Opis S.r.l.","duties_or_roles":"TMF archive - Activation sites activities","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Collection of safety laboratory assessments, biomarkers, PK and Genetics blood samples.","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Randomization Management of drug supply logistics and dispensing","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Eurofins Central Laboratory B.V.","duties_or_roles":"Analysis urine biomarkers","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Labcorp Central Laboratory Services LP","duties_or_roles":"aHUS related genetic abnormalities testing & anti-FH Ab titer, subcontracted to Machaon Diagnostics.","organisation_type":"Pharmaceutical company"}
• {"country":"India","full_name":"Veeda Clinical Research Limited","duties_or_roles":"Compound Pharmacokinetics (PK) analysis, PK sample analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"Provided services (code 1) - unspecified in listing","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Novartis Pharmaceuticals Corp.","duties_or_roles":"Long term storage","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"Provided services (code 12)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Yprime LLC","duties_or_roles":"PRO management, PRO licensing and translations, data collection via tablet, PRO assessment","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"Collection and analyses of aHUS related genetic abnormalities & Anti-FH antibody titer. Subcontracted to Machaon Diagnostics","organisation_type":"Pharmaceutical company"}