Clinical trial NCT05985915: A Randomized, Double-blind 2-arm NEPTUNUS Extension Study to Assess the Long-term Safety and Efficacy of Ianalumab in Patients With Sjogrens Syndrome.
Official title: A Randomized, Double-blind 2-arm NEPTUNUS Extension Study to Assess the Long-term Safety and Efficacy of Ianalumab in Patients With Sjogrens Syndrome.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Sjogrens Syndrome
Keywords: Sjogrens Syndrome
ianalumab
VAY736
NEPTUNUS
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2023-08-14
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to measure the long-term safety and tolerability of ianalumab in participants with Sjogrens syndrome who have previously completed treatment from one of two NEPTUNUS 1 year core studies (CVAY736A2301 \[NCT05350072\] or CVAY736A2302 \[NCT05349214\]).

* The study treatment is ianalumab 300 mg in a 2 mL pre-filled syringe (PFS) or in a 2 mL autoinjector (AI) for injection. All participants will receive ianalumab either monthly or every 3 months.
* The treatment duration will be 3 years with an additional up to 2-year safety follow-up. The total duration of this extension study will be up to 5 years.
* The visit frequency will be monthly during both the treatment period and mandatory follow-up, and then less frequently during the subsequent conditional follow-up.

Treatment of interest: The randomized treatment (ianalumab) will be received monthly or every 3 months. Participants assigned to treatment every 3 months will receive placebo every month between the ianalumab doses to maintain blinding.

Number of Participants: Approximately 600 participants from the NEPTUNUS core studies will be rolled over into the extension study.

Treatment Groups:There will be no screening period in this trial. From Week 48 of the NEPTUNUS core study, participants will be given the opportunity to consent to this extension study. From Week 52 of the NEPTUNUS core studies (i.e., Day 1 in the extension study), eligible participants will be assigned to either one of the treatment regimens:

* ianalumab 300 mg monthly or
* ianalumab 300 mg once every 3 months

Participants receiving placebo in either of the NEPTUNUS core studies will be randomized 1:1 to receive ianalumab 300 mg monthly or every 3 months starting from Week 60 and participants receiving ianalumab in either of the NEPTUNUS core studies will continue the same treatment in the extension study.

Ianalumab will be given as a subcutaneous injection from a 2 mL pre-filled syringe or a 2 mL autoinjector. Participants will be given the opportunity to self-inject at home on some visits after receiving training.

Detailed description: The primary purpose of this 3-year treatment extension study is the continued evaluation of the safety and tolerability of treatment with ianalumab 300 mg monthly or every 3 months. An additional purpose is to explore the long-term efficacy of both dosing regimens of ianalumab 300 mg.

Trial Design: This is a multicenter, randomized, double-blind, phase 3 study to assess the long-term safety and tolerability of four treatment regimens of ianalumab in participants with Sjogrens syndrome who have taken part in and completed one of two NEPTUNUS core studies, NEPTUNUS-1 (CVAY736A2301) or NEPTUNUS-2 (CVAY736A2302). There will be no screening period in this trial. From week 48 of the NEPTUNUS core study, participants will be given the opportunity to consent to this extension study. Eligible participants will continue their assigned treatment to receive ianalumab 300 mg either monthly or every 3 months for up to 3 additional years of treatment beyond the 1-year core study period. After the treatment period, all participants will enter a follow-up period to be monitored for at least 20 weeks and then a conditional (if B-cell recovery criteria have not been met) follow-up period. The total post treatment follow-up period is up to 2 years.

Study Population: Participants with Sjogrens syndrome who have completed treatment in one of two NEPTUNUS core studies.

Study treatment assignment method: Participants randomized to ianalumab 300 mg monthly or every 3 months in one of the NEPTUNUS core studies will continue their assigned treatment. Participants randomized to placebo in the NEPTUNUS core studies will be randomized in a 1:1 ratio to either ianalumab 300 mg monthly or every 3 months.

Participants randomized to ianalumab 300 mg every 3 months will receive placebo (a dummy treatment) once monthly between doses.

Committees: An independent Data Monitoring Committee (DMC) will be utilized for safety review throughout the study. A steering committee will be formed to ensure overview of the study conduct.

Eligibility criteria: Inclusion Criteria:

1. Signed informed consent prior to participation in the extension study.
2. Participants must have participated in either one of the two NEPTUNUS core studies, CVAY736A2301 or CVAY736A2302, and must have completed the entire treatment up to Week 48 without treatment discontinuation in core NEPTUNUS studies.
3. In the judgement of the Investigator, participants must be expected to clinically benefit from continued ianalumab therapy.

Exclusion Criteria:

1. Use of therapies excluded by the NEPTUNUS-1 and NEPTUNUS-2 study protocols (see NEPTUNUS studies protocols exclusion criteria in Section 5.2 for details).
2. Plans for administration of live vaccines during the study period.
3. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human Chorionic Gonadotropin (hCG) laboratory test.
4. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment during dosing and for 6 months after stopping of investigational drug. Highly effective contraception methods include:

   * Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
   * Female bilateral tubal ligation, female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or total hysterectomy at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
   * Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant.
   * Use of oral (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception.

   In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment.

   Contraception should be used in accordance with locally approved prescribing information of concomitant medications administered.

   Women are considered post-menopausal if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age-appropriate history of vasomotor symptoms). Women are considered of not child-bearing potential if they are post-menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment is she considered not of child-bearing potential.

   If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the informed consent form (ICF).
5. United States (and other countries, if male contraception is locally required): Sexually active males, unless they agree to use barrier protection during intercourse with a woman of child-bearing potential, while taking study treatment. As condom use alone has a reported failure rate exceeding 1% per year, it is recommended that female partners of male study participants use a second method of birth control. Although ianalumab is not teratogenic and/or genotoxic, and not transferred to semen, male contraception is required, as requested by FDA.

Globally, for all sexually active males, contraception should be used in accordance with the locally approved prescribing information of concomitant medications administered.

Primary outcomes:
measure: Number of Treatment-emergent AEs (TEAEs)/SAEs
timeFrame: Week 52 to Week 304
Secondary outcomes:
measure: ESSDAI change from baseline
timeFrame: Over time up to Week 204
measure: Percentage of participants achieving ESSPRI ≤ 3 AND ≥ 1.5 points reduction from baseline
timeFrame: Over time up to Week 204
measure: Percentage of participants achieving meaningful improvement in the SSSD score
timeFrame: Over time up to Week 204
measure: Pre-dose Ianalumab serum concentrations
timeFrame: pre-dose at Week 48 (from core study) and Week 64
measure: On-treatment Ianalumab serum concentrations
timeFrame: During treatment (from Week 52 to Week 204) and follow-up (From Week 208 to Week 304)
measure: B-cell count measurement
timeFrame: Week 52 to Week 304
Other outcomes:
Locations:
city: Fullerton
country: United States
facility: Providence Medical Foundation
state: California
city: La Palma
country: United States
facility: Advanced Medical Research
state: California
city: Van Nuys
country: United States
facility: Medvin Clinical Research
state: California
city: Brandon
country: United States
facility: Bay Area Arthritis And Osteoporosis
state: Florida
city: Hollywood
country: United States
facility: GNP Research
state: Florida
city: Sarasota
country: United States
facility: Sarasota Arthritis Res Ctr
state: Florida
city: Tamarac
country: United States
facility: West Broward Rheumatology Associates Inc
state: Florida
city: Augusta
country: United States
facility: Augusta University Georgia
state: Georgia
city: Suwanee
country: United States
facility: North GA Rheumatology Group PC
state: Georgia
city: Orland Park
country: United States
facility: Clin Invest Specialists Inc
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Baton Rouge
country: United States
facility: Ochsner Health System
state: Louisiana
city: Baltimore
country: United States
facility: The John Hopkins Jerome L Greene Sjogren
state: Maryland
city: Boston
country: United States
facility: Tufts School of Dental Medicine
state: Massachusetts
city: Las Cruces
country: United States
facility: Arthritis Osteoporosis Assoc of NM
state: New Mexico
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
city: Potsdam
country: United States
facility: St Lawrence Health System
state: New York
city: Charlotte
country: United States
facility: On Site Clinical Solutions Llc
state: North Carolina
city: Charlotte
country: United States
facility: Arthritis and Osteoporosis
state: North Carolina
city: Dayton
country: United States
facility: STAT Research Inc
state: Ohio
city: Oklahoma City
country: United States
facility: RAO Research LLS
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clin Res
state: Pennsylvania
city: Jackson
country: United States
facility: West Tennessee Research Institute
state: Tennessee
city: Memphis
country: United States
facility: Shelby Research LLC
state: Tennessee
city: Colleyville
country: United States
facility: Precision Comprehensive Research
state: Texas
city: Houston
country: United States
facility: Baylor College Of Medicine
state: Texas
city: Houston
country: United States
facility: Prolato Clinical Research Center
state: Texas
city: Katy
country: United States
facility: Houston Rheumatology & Arthrit
state: Texas
city: San Antonio
country: United States
facility: First Outpatient Research Unit
state: Texas
city: Spring
country: United States
facility: Advanced Rheumatology of Houston
state: Texas
city: Spokane
country: United States
facility: Arthritis Northwest PLLC
state: Washington
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Quilmes
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Tucuman
country: Argentina
facility: Novartis Investigative Site
state: San Miguel De Tucuman
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Ciudad Autonoma de Bs As
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facility: Novartis Investigative Site
city: Maroochydore
country: Australia
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state: Queensland
city: Woodville South
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state: South Australia
city: Hobart
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state: Tasmania
city: Graz
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city: Stockerau
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city: Leuven
country: Belgium
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city: Salvador
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state: BA
city: Vitoria
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state: ES
city: Juiz de Fora
country: Brazil
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state: MG
city: Ribeirao Preto
country: Brazil
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state: SP
city: Sao Paulo
country: Brazil
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state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
city: Burgas
country: Bulgaria
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city: Sofia
country: Bulgaria
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city: Vancouver
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state: British Columbia
city: Sydney
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state: Nova Scotia
city: Rimouski
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state: Quebec
city: Sherbrooke
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city: Trois Rivieres
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state: Quebec
city: Valdivia
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city: Santiago
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state: RM
city: Concepcion
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city: Santiago
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city: Santiago
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facility: Novartis Investigative Site
city: Hefei
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state: Anhui
city: Chongqing
country: China
facility: Novartis Investigative Site
state: Chongqing
city: Guangzhou
country: China
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state: Guangdong
city: Shenzhen
country: China
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state: Guangdong
city: Wuhan
country: China
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state: Hubei
city: Baotou
country: China
facility: Novartis Investigative Site
state: Inner Mongolia
city: Nanjing
country: China
facility: Novartis Investigative Site
state: Jiangsu
city: Nanchang
country: China
facility: Novartis Investigative Site
state: Jiangxi
city: Pingxiang
country: China
facility: Novartis Investigative Site
state: Jiangxi
city: Chang Chun
country: China
facility: Novartis Investigative Site
state: Jilin
city: Shenyang
country: China
facility: Novartis Investigative Site
state: Liaoning
city: Linyi
country: China
facility: Novartis Investigative Site
state: Shandong
city: Taiyuan
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Taiyuan
country: China
facility: Novartis Investigative Site
state: Shanxi
city: Chengdu
country: China
facility: Novartis Investigative Site
state: Sichuan
city: Yinchuan City
country: China
facility: Novartis Investigative Site
state: The Ningxia Hui Autonomous Reg
city: Beijing
country: China
facility: Novartis Investigative Site
city: Beijing
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facility: Novartis Investigative Site
city: Beijing
country: China
facility: Novartis Investigative Site
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Shanxi
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Xinxiang
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facility: Novartis Investigative Site
city: Medellin
country: Colombia
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state: Antioquia
city: Barranquilla
country: Colombia
facility: Novartis Investigative Site
state: Atlantico
city: Bucaramanga
country: Colombia
facility: Novartis Investigative Site
state: Santander
city: Bogota
country: Colombia
facility: Novartis Investigative Site
city: Brno
country: Czechia
facility: Novartis Investigative Site
city: Uherske Hradiste
country: Czechia
facility: Novartis Investigative Site
city: Angers Cedex 9
country: France
facility: Novartis Investigative Site
city: Brest
country: France
facility: Novartis Investigative Site
city: Dijon
country: France
facility: Novartis Investigative Site
city: Le Kremlin Bicetre
country: France
facility: Novartis Investigative Site
city: Le Mans
country: France
facility: Novartis Investigative Site
city: Lille
country: France
facility: Novartis Investigative Site
city: Paris cedex 10
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: St Etienne
country: France
facility: Novartis Investigative Site
city: Strasbourg
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Erlangen
country: Germany
facility: Novartis Investigative Site
city: Freiburg
country: Germany
facility: Novartis Investigative Site
city: Hannover
country: Germany
facility: Novartis Investigative Site
city: Herne
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Ludwigshafen
country: Germany
facility: Novartis Investigative Site
city: Wuerzburg
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala City
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala
country: Guatemala
facility: Novartis Investigative Site
city: Guatemala
country: Guatemala
facility: Novartis Investigative Site
city: Quetzaltenango
country: Guatemala
facility: Novartis Investigative Site
city: Szekesfehervar
country: Hungary
facility: Novartis Investigative Site
state: Fejer
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Eger
country: Hungary
facility: Novartis Investigative Site
city: Gyula
country: Hungary
facility: Novartis Investigative Site
city: Szeged
country: Hungary
facility: Novartis Investigative Site
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: New Delhi
country: India
facility: Novartis Investigative Site
city: Kfar Saba
country: Israel
facility: Novartis Investigative Site
city: Ramat Gan
country: Israel
facility: Novartis Investigative Site
city: Ancona
country: Italy
facility: Novartis Investigative Site
state: AN
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Salerno
country: Italy
facility: Novartis Investigative Site
state: SA
city: Napoli
country: Italy
facility: Novartis Investigative Site
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Kitakyushu
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Sapporo city
country: Japan
facility: Novartis Investigative Site
state: Hokkaido
city: Yokohama
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Kuwana
country: Japan
facility: Novartis Investigative Site
state: Mie
city: Sasebo
country: Japan
facility: Novartis Investigative Site
state: Nagasaki
city: Kurashiki
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chuo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Itabashi-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Meguro-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho Gu
city: Gwangju
country: Korea, Republic of
facility: Novartis Investigative Site
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
city: Ciudad de Mexico
country: Mexico
facility: Novartis Investigative Site
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Novartis Investigative Site
state: Jalisco
city: Culiacan
country: Mexico
facility: Novartis Investigative Site
state: Sinaloa
city: Merida
country: Mexico
facility: Novartis Investigative Site
state: Yucatan
city: Mexico
country: Mexico
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
state: Dolnoslaskie
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
state: Dolnoslaskie
city: Krakow
country: Poland
facility: Novartis Investigative Site
state: Malopolskie
city: Poznan
country: Poland
facility: Novartis Investigative Site
state: Wielkopolskie
city: Bydgoszcz
country: Poland
facility: Novartis Investigative Site
city: Krakow
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Braga
country: Portugal
facility: Novartis Investigative Site
city: Guarda
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Lisboa
country: Portugal
facility: Novartis Investigative Site
city: Brasov
country: Romania
facility: Novartis Investigative Site
city: Bucuresti
country: Romania
facility: Novartis Investigative Site
city: Cluj Napoca
country: Romania
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Bratislava
country: Slovakia
facility: Novartis Investigative Site
city: Kosice
country: Slovakia
facility: Novartis Investigative Site
city: Zvolen
country: Slovakia
facility: Novartis Investigative Site
city: Panorama
country: South Africa
facility: Novartis Investigative Site
city: Stellenbosch
country: South Africa
facility: Novartis Investigative Site
city: Cordoba
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sabadell
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Santander
country: Spain
facility: Novartis Investigative Site
state: Cantabria
city: Badalona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: La Coruna
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Bilbao
country: Spain
facility: Novartis Investigative Site
state: Pais Vasco
city: Vigo
country: Spain
facility: Novartis Investigative Site
state: Pontevedra
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Valencia
country: Spain
facility: Novartis Investigative Site
city: Stockholm
country: Sweden
facility: Novartis Investigative Site
state: SE
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Taichung
country: Taiwan
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Kocaeli
country: Turkey
facility: Novartis Investigative Site
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: Liverpool
country: United Kingdom
facility: Novartis Investigative Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: