A Rollover Extension Program (REP) to Evaluate the Long-term Safety and Tolerability of Open Label Iptacopan/LNP023 in Participants With Primary IgA Nephropathy

Primary IgA Nephropathy Clinical Trial

Official title:

A Multicenter Rollover Extension Program (REP) to Evaluate the Long-term Safety and Tolerability of Open Label Iptacopan in Adult Participants With Primary IgA Nephropathy Who Have Completed Study CLNP023X2203 or CLNP023A2301

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04557462
• Other study ID #: CLNP023A2002B
• Secondary ID: 2020-002200-40
• Status: Recruiting
• Phase: Phase 3
• Start date: September 20, 2021
• Est. completion date: May 31, 2032

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: 1-888-669-6682
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the long-term safety and tolerability, of open label iptacopan in primary IgA nephropathy participants who have completed either the CLNP023X2203 or CLNP023A2301 clinical trials. The open-label design of the current study is appropriate to provide study participants the opportunity to receive treatment with iptacopan until marketing authorizations are received and the drug product becomes commercially available while enabling collection of long-term safety and tolerability data for the investigational drug. Furthermore efficacy assessments conducted every 6 months will afford the opportunity to evaluate the clinical effects of iptacopan on long-term disease progression.

Description:

This is an open-label, non-randomized, multicenter roll-over extension program (REP) to:

• CLNP023X2203, a Phase II trial investigating the dose ranging effects of LNP023 on efficacy, pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability in primary IgAN patients, and

• CLNP023A2301, a Phase III trial, investigating the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), safety and tolerability of LNP023 in patients with primary IgAN.

Subjects completing the CLNP023X2203 and CLNP023A2301 trials on study drug, who want to continue treatment and who meet the inclusion/exclusion requirements of the roll over extension program, will have the opportunity to receive iptacopan until:

• 3 years from LPFV of this study CLNP023A2002B, or

• the participant no longer derives benefit from iptacopan according to the Investigator, or

• the benefit-risk profile of the product in IgAN is no longer positive, or

• initiation of maintenance hemodialysis, kidney transplantation or eGFR < 15 mL/min/1.73m2 , or

• the product becomes commercially available in a specific country following product launch and subsequent reimbursement for IgAN, where applicable, or

• if a marketing application or reimbursement of an investigational product is rejected/not pursued in a region/country for the indication under study or which ever is sooner

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: May 31, 2032
• Est. primary completion date: May 31, 2032
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• For LNP023X2203, participants must have completed part 1 or part 2 of the trial. For LNP023A2301, participants must have completed the entire core trial defined as the full 24 month treatment period.

• 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)

• Per investigator's clinical judgement, the participant may benefit from receiving the open-label treatment of iptacopan 200 mg b.i.d.

• 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.

• All participants must be on supportive care regimen of ACEi or ARB* as per KDIGO guidelines.

• participants who are not taking KDIGO guideline doses because they have documented allergies or intolerance to ACEi and ARB are eligible for the study

Exclusion Criteria:

• participants who screen or baseline failed in the CLNP023X2203 Part 1 or Part 2, or CLNP023A2301 studies or who prematurely withdrew from either study for any reason.

• Evidence of severe urinary obstruction or difficulty in voiding; any urinary tract disorder other than IgAN at screening and before dosing with LNP023.

• Current (within 4 weeks of study drug administration in the REP) acute kidney injury (AKI)

• Presence of Rapidly Progressive Glomerulonephritis (RPGN) as defined by 50% decline in eGFR within the last 3 months.

• Participants treated with immunosuppressive or other immunmodulatory 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 5 half-lives of respective medication or 90 days prior to first study drug administration, whichever is shorter. Rituximab requires 180 days wash out.

• Use of other investigational drugs at the time of enrolment, or within 5 half-lives of enrolment or within 30 days whichever is longer.

• History of recurrent invasive infections caused by encapsulated organisms, such as meningococcus and pneumococcus.

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• Kidney Diseases
• Primary IgA Nephropathy

Intervention

Drug:
• LNP023
Capsule 200 mg (b.i.d.) taken orally twice a day

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Cordoba
Argentina	Novartis Investigative Site	Santa Fe
Australia	Novartis Investigative Site	Adelaide	South Australia
Australia	Novartis Investigative Site	Parkville	Victoria
Belgium	Novartis Investigative Site	Edegem	Antwerpen
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Roeselare
Brazil	Novartis Investigative Site	Curitiba	PR
Brazil	Novartis Investigative Site	Porto Alegre	RS
Brazil	Novartis Investigative Site	Sao Paulo	SP
Brazil	Novartis Investigative Site	São Paulo	SP
Canada	Novartis Investigative Site	Oshawa	Ontario
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Guangzhou	Guangdong
China	Novartis Investigative Site	Qingdao
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Shanxi
China	Novartis Investigative Site	Yinchuan	Ningxia
Czechia	Novartis Investigative Site	Praha
Denmark	Novartis Investigative Site	Aalborg
Denmark	Novartis Investigative Site	Arhus N
Denmark	Novartis Investigative Site	Copenhagen
France	Novartis Investigative Site	Paris
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Mainz
Hong Kong	Novartis Investigative Site	Hong Kong SAR
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	New Delhi
Israel	Novartis Investigative Site	Ashkelon
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Petach Tikva
Italy	Novartis Investigative Site	Napoli
Japan	Novartis Investigative Site	Kyoto
Japan	Novartis Investigative Site	Matsumoto	Nagano
Japan	Novartis Investigative Site	Okayama-city	Okayama
Japan	Novartis Investigative Site	Omihachiman	Shiga
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Sapporo	Hokkaido
Japan	Novartis Investigative Site	Sapporo-city	Hokkaido
Japan	Novartis Investigative Site	Sendai	Miyagi
Japan	Novartis Investigative Site	Toyoake city	Aichi
Japan	Novartis Investigative Site	Toyota	Aichi
Japan	Novartis Investigative Site	Yokohama-city	Kanagawa
Korea, Republic of	Novartis Investigative Site	Cheongju si	Chungcheongbuk Do
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho Gu
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Taegu
Malaysia	Novartis Investigative Site	Kuala Lumpur
Malaysia	Novartis Investigative Site	Kuala Lumpur
Netherlands	Novartis Investigative Site	Groningen
Norway	Novartis Investigative Site	Bergen
Norway	Novartis Investigative Site	Nordbyhagen	Oslo
Russian Federation	Novartis Investigative Site	Rostov On Don
Russian Federation	Novartis Investigative Site	St. Petersburg
Singapore	Novartis Investigative Site	Singapore
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taichung
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taoyuan
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Bangkok
Turkey	Novartis Investigative Site	Istanbul	TUR
Turkey	Novartis Investigative Site	Kocaeli
Turkey	Novartis Investigative Site	Talas / Kayseri
United Kingdom	Novartis Investigative Site	Cambridge	Cambrigdeshire
United Kingdom	Novartis Investigative Site	Leicester
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Newcastle Upon Tyne
United Kingdom	Novartis Investigative Site	Salford	Manchester
United States	University of Colorado Anschutz	Aurora	Colorado
United States	AZ Kidney Dise and Hypertension Ctr	Glendale	Arizona
United States	Prolato Clinical Research Center	Houston	Texas
United States	Clinical Research Consultants LLC	Kansas City	Missouri
United States	DaVita Clinical Research	Las Vegas	Nevada
United States	Nephrology Associates PA	Newark	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Brazil,  Canada,  China,  Czechia,  Denmark,  France,  Germany,  Hong Kong,  India,  Israel,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Netherlands,  Norway,  Russian Federation,  Singapore,  Taiwan,  Thailand,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and percentage of participants with serious adverse event	Summary statistics on serious adverse events	Date of first administration of (Day 1) to 7 days after the date of the last actual administration of study treatment
Primary	Number and percentage of participants with adverse event	Summary statistics on adverse events	Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual administration of study treatment
Primary	Number and percentage of participants with adverse events of special interest	Summary statistics on adverse events of special interest	Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual adminstration of study treatment
Primary	Number and percentage of participants with abnormalities in vital signs	Summary statistics on abnormalities in vital sign parameters	Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual administration of study treatment
Primary	Number and percentage of participants with abnormalities in ECG	Summary statistics in abnormalities in ECG parameters	Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual administration of study treatment
Primary	Number and percentage of participants with abnormalities in clinical laboratory evaluations	Summary statistics on abnormalities in clinical laboratory evaluations	Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual administration of study treatment
Secondary	Annualized total eGFR slope	Annualized rate of renal disease progression as measured by mean eGFR slope at post baseline visits	Screening visit, Months 1, 3, 6, 9, 12 and every 6 months thereafter
Secondary	Change from baseline in eGFR	Average change from baseline in eGFR at post-baseline visits	Screening visit, Months 1, 3, 6, 9, 12 and every 6 months thereafter
Secondary	Log transformed ratio to baseline in UPCR, UACR	Log transformed ratio to baseline in UPCR, UACR at post-baseline visits. The log transformation refers to the natural log (base on e)	Screening visit, Months 1, 3, 6, 9, 12 and every 6 months thereafter