A multicenter, single-arm, open-label study to evaluate efficacy and safety of switching from anti-C5 antibody treatment to iptacopan treatment in study participants with aHUS

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novartis Pharma AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

3 Apr 2025 → ongoing

Decision date (initial)

2024-02-02

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Pharmacogenetic, Safety, Therapy, Others

To assess the proportion of participants free of TMA manifestation during the 12 months of iptacopan treatment following the switch of treatment from an anti-C5 antibody to iptacopan treatment

Secondary objectives 6

1. To assess the proportion of participants free of TMA manifestation during 12 months of iptacopan treatment following the switch of treatment from an anti-C5 antibody to iptacopan in study participants with functionally significant mutations in complement genes (i.e., C3, CD46, FH, FI, FB), and/or tested positive for anti-FH antibodies.
2. To assess time to TMA manifestation following the switch of treatment from an anti-C5 antibody to iptacopan treatment
3. To assess the effect of iptacopan treatment on hematologic parameters (platelets, LDH and hemoglobin) and kidney function (serum creatinine, UPCR, eGFR, chronic kidney disease (CKD) stage) at Month 12
4. To assess the effect of iptacopan study treatment on dialysis requirement status
5. To assess safety and tolerability of iptacopan treatment.
6. To evaluate proportion of participants with Thrombotic Microangiopathy (TMA) related events

Conditions and MedDRA coding

Atypical Hemolytic Uremic Syndrome (aHUS)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Signed informed consent must be obtained prior to participation in the study
2. Male and female participants ≥ 18 years of age at the time of consent.
3. Willing and able to comply with the study visit schedule
4. 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.
5. 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 .
6. 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: • Hematological 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 .
7. 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
8. 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 18

1. History of aHUS disease relapse while on anti-C5 antibody treatment.
2. 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: • Any single parameter of alanine amino transferase (ALT), gamma-glutamyl transferase (GGT), alkaline phosphatase must not exceed 3×upper limit of normal (ULN).
3. Any medical condition deemed likely to interfere with the participant’s participation in the study.
4. 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.
5. History of hypersensitivity to iptacopan or any of its excipients or to drugs of similar chemical classes.
6. 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
7. Female participants who are pregnant or breastfeeding, or intending to conceive during the course of the study.
8. 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.
9. eGFR < 30 ml/min/1.73m2.
10. Uncontrolled arterial hypertension (systolic blood pressure >160 mmHg).
11. Active infection or history of recurrent invasive infections caused by encapsulated bacteria, i.e. meningococcus, pneumococcus (eg., N. meningitidis, S. pneumoniae) or H. influenzae.
12. Participants with sepsis or active systemic bacterial, viral (including COVID-19) or fungal infection within 14 days prior to study treatment administration.
13. Human immunodeficiency virus (HIV) infection (known history of HIV or test positive for HIV at screening).
14. 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.
15. History of drug or alcohol abuse within the 12 months prior to dosing.
16. 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).
17. Participants committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
18. Participants dependent on the sponsor, the study site or the Investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 6

1. 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.
2. Time to TMA manifestation during 12 Months of iptacopan treatment
3. Change from baseline in hematologic parameters (platelets, LDH, hemoglobin) and kidney function (serum creatinine, UPCR, eGFR, CKD stage) at Month 12 of iptacopan treatment.
4. Dialysis requirement status (YES/NO) through 12 months of iptacopan treatment
5. Safety evaluations during 12 months of iptacopan treatment (including adverse events/serious adverse events, safety laboratory parameters and vital signs)
6. TMA related events during 12 months of iptacopan treatment. TMA related events are defined as any of the following: • Irreversible (>3 months) reduction in estimated glomerular filtration rate (eGFR) 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel Town

Postcode

4056

Country

Switzerland

Scientific contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Public contact point

Organisation

Novartis Pharma AG

Contact name

Novartis Pharma Arzneimittel GmbH

Third parties 20

Locations

4 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 45 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications