A rollover extension program (REP) to evaluate the long-term safety and tolerability of open label iptacopan in adult participants with primary IgA nephropathy

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

20 Sep 2021 → ongoing

Decision date (initial)

2024-05-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-508690-92-00

EudraCT number

2020-002200-40

ClinicalTrials.gov

NCT04557462

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Therapy, Efficacy, Safety, Others

The primary objective is to evaluate the long-term safety and tolerability
of iptacopan in eligible participants.

Secondary objectives 1

1. The secondary objective is to characterize the clinical benefit (efficacy) of iptacopan in eligible participants receiving open-label iptacopan.

Conditions and MedDRA coding

IgA Nephropathy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Signed informed consent must be obtained prior to participation in the REP; participants should be able to communicate well with the Investigator, understand and comply with the requirements of the study.
2. For CLNP023X2203, participants must have completed Part 1 or Part 2 of the trial. For other parent trials participants must have completed the entire parent trial duration defined by the respective protocol.
3. eGFR* ≥ 20 mL/min/1.73m2. *eGFR calculated using the CKD-EPI formula (or modified MDRD formula according to specific ethnic groups and local practice guidelines).
4. Per Investigator’s clinical judgment, the participant may benefit from receiving the open-label treatment of iptacopan 200 mg b.i.d.
5. Prior vaccination against Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae infections should be up to date (i.e. any boosters required administered according to local regulations).
6. All participants must be on supportive care regimen of stable dose of ACEi or ARB* as per KDIGO guidelines (KDIGO 2021). * Participants with allergies or intolerance to ACEi and ARB are eligible for the study but the Investigator should clearly document the reasons for not being on maximal ACEi/ARB dose in the source documents.

Exclusion criteria 17

1. Participants who are screen or baseline failed in any of the iptacopan parent studies in IgAN or who prematurely withdrew from iptacopan parent studies in IgAN for any reason.
2. Evidence of severe urinary obstruction or difficulty in voiding; any urinary tract disorder other than IgAN at screening and before dosing with iptacopan.
3. Current (within 4 weeks prior to study treatment administration in the REP) acute kidney injury (AKI) defined by AKIN criteria.
4. Presence of Rapidly Progressive Glomerulonephritis (RPGN) as defined by 50% decline in eGFR within the last 3 months.
5. Participants treated with immunosuppressive or other immunomodulatory agents such as but not limited to cyclophosphamide, rituximab, infliximab, eculizumab, canakinumab, mycophenolate mofetil (MMF) or mycophenolate sodium (MPS), cyclosporine, tacrolimus, sirolimus, everolimus and/or systemic corticosteroids exposure (>7.5 mg/d prednisone/prednisolone equivalent) within 90 days prior to first study drug administration. Rituximab requires 180 days wash out. Participants treated with endothelin (receptor) antagonists within 90 days prior to first study drug administration.
6. Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment or within 30 days whichever is longer
7. History of recurrent invasive infections caused by encapsulated organisms, such as Neisseria meningitidis, Streptococcus pneumoniae and Hemophilus influenzae.
8. All transplanted participants (any solid organ, or bone marrow transplantation).
9. Major concurrent comorbidities including but not limited to severe uncontrolled hypertension, other chronic kidney disease (with or without kidney failure), advanced cardiac disease (e.g., NYHA class IV), severe pulmonary disease (e.g., severe pulmonary hypertension (WHO class IV), or hepatic disease (e.g. active hepatitis) that in the opinion of the Investigator precludes participant's participation in the study.
10. Any medical condition deemed likely to interfere with the participant’s participation in the study.
11. Active systemic bacterial, viral (including COVID-19) or fungal infection within 14 days prior to study treatment administration.
12. Presence of fever ≥ 38°C (100.4°F) within 7 days prior to study treatment administration.
13. History of Human Immunodeficiency Virus (HIV) infection (known history of HIV or test positive for HIV antibody at Screening).
14. Liver disease or liver injury as indicated by abnormal liver function tests (LFT) at screening as defined below. ALT (SGPT), AST (SGOT), GGT, alkaline phosphatase and serum bilirubin will be tested. • Any single parameter of ALT, AST, GGT, alkaline phosphatase must not exceed 3 × upper limit of normal (ULN) • Serum bilirubin must not exceed 2 × ULN Participants from CLNP023X2203 study or any other parent study participants if required by local regulations will be additionally tested for HBsAg and HCV-RNA and are not eligible if the results are positive.
15. History of hypersensitivity to any of the study treatments or its excipients or to drugs of similar chemical classes or any participant who discontinued study treatment in the parent study due to a suspected treatment-related AE.
16. History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer treated with curative intent), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
17. Pregnant or breastfeeding females, where pregnancy is confirmed by a positive Human Chorionic Gonadotrophin (HCG) test.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety and tolerability endpoints (including but not limited to AEs/SAEs, safety laboratory parameters, vital signs).

Secondary endpoints 3

1. Annualized total eGFR slope.
2. Change from baseline in eGFR.
3. Log transformed ratio to baseline in UPCR, UACR.

Investigational products

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

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novartis Pharma AG

Sponsor organisation

Novartis Pharma AG

Address

Lichtstrasse 35

City

Basel

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 14

Locations

13 EU/EEA countries · 38 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 83 files

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

Application history

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