Clinical trial NCT04557462: A Rollover Extension Program (REP) to Evaluate the Long-term Safety and Tolerability of Open Label Iptacopan/LNP023 in Participants With Primary IgA Nephropathy
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Primary IgA Nephropathy
Keywords: Immunoglobulin A nephropathy
Primary IgA nephropathy
IgAN
chronic kidney disease
glomerulonephritis
complement alternative pathway
eGFR
UPCR
UACR
LNP023
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2020-09-21
Enrollment: 540
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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

Eligibility criteria: 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.

Primary outcomes:
measure: Number and percentage of participants with serious adverse event
timeFrame: Date of first administration of (Day 1) to 7 days after the date of the last actual administration of study treatment
measure: Number and percentage of participants with adverse event
timeFrame: Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual administration of study treatment
measure: Number and percentage of participants with adverse events of special interest
timeFrame: Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual adminstration of study treatment
measure: Number and percentage of participants with abnormalities in vital signs
timeFrame: Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual administration of study treatment
measure: Number and percentage of participants with abnormalities in ECG
timeFrame: Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual administration of study treatment
measure: Number and percentage of participants with abnormalities in clinical laboratory evaluations
timeFrame: Date of first administration of study treatment (Day 1) to 7 days after the date of the last actual administration of study treatment
Secondary outcomes:
measure: Annualized total eGFR slope
timeFrame: Screening visit, Months 1, 3, 6, 9, 12 and every 6 months thereafter
measure: Change from baseline in eGFR
timeFrame: Screening visit, Months 1, 3, 6, 9, 12 and every 6 months thereafter
measure: Log transformed ratio to baseline in UPCR, UACR
timeFrame: Screening visit, Months 1, 3, 6, 9, 12 and every 6 months thereafter
Other outcomes:
Locations:
city: Glendale
country: United States
facility: AZ Kidney Dise and Hypertension Ctr
state: Arizona
city: San Diego
country: United States
facility: Kaiser Permanente
state: California
city: San Dimas
country: United States
facility: North America Research Institute
state: California
city: Aurora
country: United States
facility: University of Colorado Anschutz
state: Colorado
city: Newark
country: United States
facility: Nephrology Associates PA
state: Delaware
city: Chubbuck
country: United States
facility: CaRe Research
state: Idaho
city: Hinsdale
country: United States
facility: Nep Assoc of Northern Illinois
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
city: Boston
country: United States
facility: Brigham and Womens Hosp Harvard Med School
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: Kansas City
country: United States
facility: Clinical Research Consultants LLC
state: Missouri
city: Las Vegas
country: United States
facility: DaVita Clinical Research
state: Nevada
city: Jersey City
country: United States
facility: New Jersey Kidney Care
state: New Jersey
city: New York
country: United States
facility: Col Uni Med Center New York Presby
state: New York
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aire
country: Argentina
facility: Novartis Investigative Site
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: Cordoba
country: Argentina
facility: Novartis Investigative Site
city: Santa Fe
country: Argentina
facility: Novartis Investigative Site
city: Woolloongabba
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Adelaide
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Edegem
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Roeselare
country: Belgium
facility: Novartis Investigative Site
city: Belo Horizonte
country: Brazil
facility: Novartis Investigative Site
state: MG
city: Curitiba
country: Brazil
facility: Novartis Investigative Site
state: PR
city: Porto Alegre
country: Brazil
facility: Novartis Investigative Site
state: RS
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Jose do Rio Preto
country: Brazil
facility: Novartis Investigative Site
city: Oshawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Beijing
country: China
facility: Novartis Investigative Site
state: Beijing
city: Guangzhou
country: China
facility: Novartis Investigative Site
state: Guangdong
city: Luoyang
country: China
facility: Novartis Investigative Site
state: Henan
city: Changsha
country: China
facility: Novartis Investigative Site
state: Hunan
city: Changchun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Yinchuan
country: China
facility: Novartis Investigative Site
state: Ningxia
city: Taiyuan
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Urumqi
country: China
facility: Novartis Investigative Site
state: Xinjiang
city: Wenzhou
country: China
facility: Novartis Investigative Site
state: Zhejiang
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Guang Zhou
country: China
facility: Novartis Investigative Site
city: Qingdao
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanxi
country: China
facility: Novartis Investigative Site
city: Shenzhen
country: China
facility: Novartis Investigative Site
city: Medellin
country: Colombia
facility: Novartis Investigative Site
state: Antioquia
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
city: Praha
country: Czechia
facility: Novartis Investigative Site
city: Aalborg
country: Denmark
facility: Novartis Investigative Site
city: Arhus N
country: Denmark
facility: Novartis Investigative Site
city: Copenhagen
country: Denmark
facility: Novartis Investigative Site
city: Odense C
country: Denmark
facility: Novartis Investigative Site
city: Marseille
country: France
facility: Novartis Investigative Site
city: Montpellier 5
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Aachen
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Heidelberg
country: Germany
facility: Novartis Investigative Site
city: Magdeburg
country: Germany
facility: Novartis Investigative Site
city: Mainz
country: Germany
facility: Novartis Investigative Site
city: Stuttgart
country: Germany
facility: Novartis Investigative Site
city: Tuebingen
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Pokfulam
country: Hong Kong
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: New Delhi
country: India
facility: Novartis Investigative Site
state: Delhi
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Ashkelon
country: Israel
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Petach Tikva
country: Israel
facility: Novartis Investigative Site
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Kasugai
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Toyoake city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Toyota
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Sapporo-city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Sapporo
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Kawasaki
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Sendai
country: Japan
facility: Novartis Investigative Site
state: Miyagi
city: Matsumoto
country: Japan
facility: Novartis Investigative Site
state: Nagano
city: Okayama-city
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Omihachiman
country: Japan
facility: Novartis Investigative Site
state: Shiga
city: Chiba
country: Japan
facility: Novartis Investigative Site
city: Kyoto
country: Japan
facility: Novartis Investigative Site
city: Niigata
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Cheongju si
country: Korea, Republic of
facility: Novartis Investigative Site
state: Chungcheongbuk do
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho gu
city: Busan
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Taegu
country: Korea, Republic of
facility: Novartis Investigative Site
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
state: Wilayah Persekutuan
city: Kuala Lumpur
country: Malaysia
facility: Novartis Investigative Site
city: Queretaro
country: Mexico
facility: Novartis Investigative Site
city: Groningen
country: Netherlands
facility: Novartis Investigative Site
city: Nordbyhagen
country: Norway
facility: Novartis Investigative Site
state: Oslo
city: Bergen
country: Norway
facility: Novartis Investigative Site
city: Rostov On Don
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Kosice
country: Slovakia
facility: Novartis Investigative Site
city: Ljubljana
country: Slovenia
facility: Novartis Investigative Site
city: Maribor
country: Slovenia
facility: Novartis Investigative Site
city: Salamanca
country: Spain
facility: Novartis Investigative Site
state: Castilla Y Leon
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Pamplona
country: Spain
facility: Novartis Investigative Site
state: Navarra
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: New Taipei City
country: Taiwan
facility: Novartis Investigative Site
city: New Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
state: TUR
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Kocaeli
country: Turkey
facility: Novartis Investigative Site
city: Mersin
country: Turkey
facility: Novartis Investigative Site
city: Talas Kayseri
country: Turkey
facility: Novartis Investigative Site
city: Cambridge
country: United Kingdom
facility: Novartis Investigative Site
city: Leicester
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
city: Salford
country: United Kingdom
facility: Novartis Investigative Site
city: Ho Chi Minh
country: Vietnam
facility: Novartis Investigative Site
state: VNM
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: