24 hetes, kettős-vak randomizált, placebo-kontrollos vizsgálat a LOU064 hatékonyságának, PK, biztonságosságának értékelésére serdülőknél (12 -
Kettős-vak, randomizált, placebo-kontrollos vizsgálat a Remibrutinib (LOU064) hatékonyságának, farmakokinetikájának és biztonságosságának értékelésére 24 hétig 12 és 18 év alatti serdülőknél krónikus spontán csalánkiütésben, amelyet nem megfelelően kezelt1-antihisztamin opcionális nyílt meghosszabbítás akár további 3 évre és opcionális biztonsági, hosszú távú kezelés nélküli követési időszak, akár további 3 évre
The purpose of this trial is:
- to assess the efficacy, pharmacokinetics, and safety of remibrutinib vs. placebo in adolescents from 12 to < 18 years of age suffering from chronic spontaneous urticaria inadequately controlled by H1-antihistamines
- to collect long-term efficacy, safety and tolerability data on remibrutinib in adolescents after having completed 24 weeks of treatment
- to collect safety data in this population for up to three years after the last dose of study treatment
A tanulmány áttekintése
Állapot
Körülmények
Beavatkozás / kezelés
Részletes leírás
This trial consists of 3 different periods:
- the "core period", which is randomized and double-blind, during which 2/3 participants will receive remibrutinib and 1/3 will receive placebo for 24 weeks. Total duration: approximately 32 weeks (10 site visits).
- an optional "open-label extension (OLE) period" proposed to all participants who completed 24 weeks of treatment of the "core period" and all scheduled assessments planned at week 24 visit . Depending on their CSU symptoms (as assessed by the doctor), participants will either receive remibrutinib for 24 weeks, or enter an observational treatment-free period for 1 year. If the CSU symptoms return during the observational period, the participants can switch to the treatment period at any time (decided by the doctor). At the end of the 24-week treatment period, if CSU is controlled, participants will enter the 1-year observational period, otherwise, they can continue with another cycle of 24-week remibrutinib treatment. The number of remibrutinib treatment or observational cycles will be limited to 6 times each. Total duration: from 1 year to approximately 3 years, and number of visits: from 3 to 15 (depending on the CSU symptoms).
- an optional "long-term treatment-free follow-up period" proposed to all participants who completed at least 4 months treatment in the "OLE period". No treatment will be given. Duration: 3 years with 1 site visit and up to 4 phone call follow-up visits.
The primary clinical question of interest is what is the effect of remibrutinib treatment versus placebo on the change from baseline in UAS7, ISS7 and HSS7 scores after 12 weeks of treatment
Tanulmány típusa
Beiratkozás (Tényleges)
Fázis
- 3. fázis
Kapcsolatok és helyek
Tanulmányi helyek
-
-
-
CABA, Argentína, C1181ACH
- Novartis Investigative Site
-
San Miguel de Tucumán, Argentína, T4000AXL
- Novartis Investigative Site
-
-
Buenos Aires
-
CABA, Buenos Aires, Argentína, C1414AIF
- Novartis Investigative Site
-
-
Santa Fe Province
-
Rosario, Santa Fe Province, Argentína, S2000DEJ
- Novartis Investigative Site
-
-
-
-
Santiago Metropolitan
-
Santiago, Santiago Metropolitan, Chile, 8420383
- Novartis Investigative Site
-
-
-
-
-
Cape Town, Dél-Afrika, 7925
- Novartis Investigative Site
-
-
Gauteng
-
Pretoria, Gauteng, Dél-Afrika, 0181
- Novartis Investigative Site
-
-
-
-
-
Manchester, Egyesült Királyság, M13 9WL
- Novartis Investigative Site
-
Southampton, Egyesült Királyság, SO16 6YD
- Novartis Investigative Site
-
-
Cambridgeshire
-
Peterborough, Cambridgeshire, Egyesült Királyság, PE3 9GZ
- Novartis Investigative Site
-
-
-
-
California
-
Bakersfield, California, Egyesült Államok, 93301
- Kern Research
-
San Diego, California, Egyesült Államok, 92123
- Allergy and Asthma Medical Group and Research Center
-
-
Florida
-
Miami, Florida, Egyesült Államok, 33156
- Pediatric Dermatology of Miami at the Pediatric CoE
-
-
Idaho
-
Boise, Idaho, Egyesült Államok, 83706
- Treasure Valley Medical Research
-
-
Illinois
-
Glenview, Illinois, Egyesült Államok, 60077
- Endeavor Health
-
-
Kentucky
-
Owensboro, Kentucky, Egyesült Államok, 42301
- Allergy and Asthma Specialist P S C
-
-
Ohio
-
Toledo, Ohio, Egyesült Államok, 43617
- Toledo Institute of Clinical Research
-
-
Oklahoma
-
Oklahoma City, Oklahoma, Egyesült Államok, 73120
- Allergy Asthma and Clinical Research
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, Egyesült Államok, 15241
- Allergy and Clinical Immunology Associates
-
-
Texas
-
San Antonio, Texas, Egyesült Államok, 78213
- RFSA Dermatology
-
-
Utah
-
Sandy City, Utah, Egyesült Államok, 84093
- Allergy Associates of Utah
-
-
-
-
-
Utrecht, Hollandia, 3584 CX
- Novartis Investigative Site
-
-
-
-
Hong Kong
-
Hong Kong, Hong Kong, Hong Kong, 999077
- Novartis Investigative Site
-
-
-
-
Fukuoka
-
Kitakyushu, Fukuoka, Japán, 8078556
- Novartis Investigative Site
-
-
Kumamoto
-
Kamimashi-gun, Kumamoto, Japán, 8613106
- Novartis Investigative Site
-
-
Osaka
-
Sakai, Osaka, Japán, 5938324
- Novartis Investigative Site
-
-
Shimane
-
Izumo, Shimane, Japán, 6938501
- Novartis Investigative Site
-
-
Tokyo
-
tabashi City, Tokyo, Japán, 1738610
- Novartis Investigative Site
-
-
-
-
Quebec
-
Montreal, Quebec, Kanada, H4A 3J1
- Novartis Investigative Site
-
-
-
-
-
Beijing, Kína, 100050
- Novartis Investigative Site
-
Beijing, Kína, 100069
- Novartis Investigative Site
-
-
Guangdong
-
Guangzhou, Guangdong, Kína, 510091
- Novartis Investigative Site
-
-
Sichuan
-
Chengdu, Sichuan, Kína, 610041
- Novartis Investigative Site
-
-
-
-
-
Lodz, Lengyelország, 90-436
- Novartis Investigative Site
-
-
-
-
Sarawak
-
Kuching, Sarawak, Malaysia, 93586
- Novartis Investigative Site
-
-
-
-
-
Berlin, Németország, 13353
- Novartis Investigative Site
-
Tübingen, Németország, 72076
- Novartis Investigative Site
-
-
Hesse
-
Frankfurt am Main, Hesse, Németország, 60590
- Novartis Investigative Site
-
-
-
-
FI
-
Florence, FI, Olaszország, 50139
- Novartis Investigative Site
-
-
PV
-
Pavia, PV, Olaszország, 27100
- Novartis Investigative Site
-
-
SI
-
Siena, SI, Olaszország, 53100
- Novartis Investigative Site
-
-
-
-
-
Valencia, Spanyolország, 46014
- Novartis Investigative Site
-
-
Barcelona
-
Esplugues, Barcelona, Spanyolország, 08950
- Novartis Investigative Site
-
-
-
-
-
Bangkok, Thaiföld, 10330
- Novartis Investigative Site
-
Bangkok, Thaiföld, 10700
- Novartis Investigative Site
-
-
Hat Yai
-
Songkhla, Hat Yai, Thaiföld, 90110
- Novartis Investigative Site
-
-
-
-
-
Adana, Törökország (Türkiye), 01330
- Novartis Investigative Site
-
-
Fatih
-
Istanbul, Fatih, Törökország (Türkiye), 34093
- Novartis Investigative Site
-
-
Sihhiye Altindag
-
Ankara, Sihhiye Altindag, Törökország (Türkiye), 06230
- Novartis Investigative Site
-
-
Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
Egészséges önkénteseket fogad
Tanulmányozható nemek
Leírás
Key Inclusion Criteria:
- Male and female adolescent participants aged >= 12 to < 18 years of age at the time of signing the informed consent
- CSU duration for >= 6 months prior to screening (defined as the onset of CSU determined by the investigator based on all available supporting documentation)
- Diagnosis of CSU inadequately controlled by second-generation H1-AH at the time of randomization defined as:
- The presence of itch and hives for ≥ 6 consecutive weeks prior to screening despite the use of second-generation H1-AH during this time period according to local treatment guidelines
- UAS7 score (range 0 - 42) >= 16, ISS7 score (range 0 - 21) >= 6 and HSS7 score (range 0 - 21) >= 6 during the 7 days prior to randomization (Day 1)
- Documentation of hives within three months before randomization (either at screening and/or at randomization; or documented in the participants' medical history)
Key Exclusion criteria:
- Previous use of remibrutinib or other BTK inhibitors
- Significant bleeding risk or coagulation disorders
- History of gastrointestinal bleeding
- Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited
- History or current hepatic disease
- Evidence of clinically significant cardiovascular, neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders, gastrointestinal disease or immunodeficiency that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant
- History of hypersensitivity to any of the study drugs or its excipients or to drugs of similar chemical classes
- Participants having a clearly defined predominant or sole trigger of their chronic urticaria (chronic inducible urticaria) including urticaria factitia (symptomatic dermographism), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergic-, or contact-urticaria
- Other diseases with symptoms of urticaria or angioedema, including but not limited to urticaria vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary angioedema, or drug-induced urticaria
- Any other skin disease associated with chronic itching that might influence in the investigator's opinion the study evaluations and results, e.g., atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or psoriasis
Other protocol-defined inclusion/exclusion criteria may apply.
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Kiosztás: Véletlenszerűsített
- Beavatkozó modell: Párhuzamos hozzárendelés
- Maszkolás: Négyszeres
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
|---|---|
|
Kísérleti: Arm 1: LOU064 (blinded)
LOU064 (blinded) taken orally b.i.d. for 24 weeks, followed by LOU064 (open-label) taken orally b.i.d. for up to 6 cycles of 24 weeks. |
LOU064 (blinded) active treatment
Más nevek:
|
|
Placebo Comparator: Arm 2: LOU064 placebo (blinded)
LOU064 placebo (blinded) taken orally b.i.d. for 24 weeks (randomized in a 2:1 ratio arm 1: arm 2) |
matching active drug |
Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
|
Change from baseline in UAS7
Időkeret: Baseline, week 12
|
The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. Complete UAS7 response is UAS7 = 0. Negative change from baseline indicates improvement. |
Baseline, week 12
|
|
Change fron baseline in ISS7
Időkeret: Baseline, Week 12
|
Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate). Negative change from baseline indicates improvement. |
Baseline, Week 12
|
|
Change from baseline in HSS7
Időkeret: Baseline, Week 12
|
Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (>12 hives/12 hours). Negative change from baseline indicates improvement. |
Baseline, Week 12
|
Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
|
Cmax of remibrutinib
Időkeret: At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
|
The maximum (peak) observed blood drug concentration after single dose administration |
At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
|
|
Tmax of remibrutinib
Időkeret: At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
|
The time to reach maximum (peak) blood drug concentration after single dose administration |
At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
|
|
AUClast of remibrutinib
Időkeret: At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
|
The Area Under the Curve (AUC) from pre-dose to the last measurable concentration sampling time |
At Week 12, before study drug intake, then after 30 min, 1 h, 2h, 3h and 4 h after study drug intake
|
|
Absolute change from baseline in ISS7
Időkeret: Baseline - Week 12
|
Itch Severity Score (ISS) scale is 0 to 3. Score (ISS7) is derived by adding up average daily scores of 7 days preceding visit. Possible range of weekly score is therefore 0 to 21. Itch Severity Score scale: 0 - None 1 - Mild (minimal awareness, easily tolerated) 2 - Moderate (definite awareness, bothersome but tolerable) 3 - Severe (difficult to tolerate). Negative change from baseline indicates improvement. |
Baseline - Week 12
|
|
Absolute change from baseline in HSS7
Időkeret: Baseline - Week 12
|
Hives Severity Score (HSS) scale is 0 to 3. A weekly score (HSS7) is derived by adding up the average daily scores of the 7 days preceding the visit. Possible range of the weekly score is therefore 0 to 21. Hives Severity Score scale: 0 - None 1 - Mild (1-6 hives/12 hours) 2 - Moderate (7-12 hives/12 hours) 3 - Severe (>12 hives/12 hours). Negative change from baseline indicates improvement. |
Baseline - Week 12
|
|
Achievement of UAS7 ≤ 6 (yes/no)
Időkeret: Week 12 and over time
|
Disease activity control is defined as UAS7 ≤ 6. The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. |
Week 12 and over time
|
|
Achievement of UAS7 = 0 (yes/no)
Időkeret: Week 12 and over time
|
Complete absence of hives and itch is defined as UAS7 = 0. The Urticaria Activity Score (UAS) is sum of the Hive Severity Score (HSS) and the Itch Severity Score (ISS). UAS7 is sum of the HSS7 and the ISS7 scores. Possible range of weekly UAS7 score is 0 to 42. |
Week 12 and over time
|
|
Absolute change from baseline in CDLQI score
Időkeret: Week 12
|
The Children Dermatology life Quality Index (CDLQI) score range is 0 to 30, with 0 (meaning no impact of skin disease on quality of life) to 30 (meaning maximum impact on quality of life). |
Week 12
|
|
Number of weeks without angioedema, assessed by the cumulative number of weeks with an AAS7 = 0 response
Időkeret: baseline - Week 12
|
Angioedema Activity Score (AAS7) is a measure of the frequency and intensity of angioedema episodes. The total possible range of scores over 7 days is 0-105 where higher scores indicate increased angioedema activity. |
baseline - Week 12
|
|
Occurrence of treatment-emergent adverse events (AE) and serious adverse events (SAE) during the core period
Időkeret: 28 weeks
|
To demonstrate the safety and tolerability of remibrutinib by assessing occurrence of treatment emergent adverse events and serious adverse events during the core period of the study. |
28 weeks
|
|
Occurrence of treatment emergent AEs, and SAEs during the Open Label Extension (OLE) period
Időkeret: 3 years
|
To demonstrate the safety and tolerability of remibrutinib by assessing occurrence of treatment emergent adverse events and serious adverse events during the OLE period of the study. |
3 years
|
Együttműködők és nyomozók
Szponzor
Nyomozók
- Tanulmányi igazgató: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete (Tényleges)
Elsődleges befejezés (Becsült)
A tanulmány befejezése (Becsült)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Tényleges)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
Kulcsszavak
További vonatkozó MeSH feltételek
Egyéb vizsgálati azonosító számok
- CLOU064F12301
- 2022-502159-78-00 (Egyéb azonosító: EU CT Number)
Terv az egyéni résztvevői adatokhoz (IPD)
Tervezi megosztani az egyéni résztvevői adatokat (IPD)?
IPD terv leírása
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Gyógyszer- és eszközinformációk, tanulmányi dokumentumok
Egy amerikai FDA által szabályozott gyógyszerkészítményt tanulmányoz
Egy amerikai FDA által szabályozott eszközterméket tanulmányoz
Ezt az információt közvetlenül a clinicaltrials.gov webhelyről szereztük be, változtatás nélkül. Ha bármilyen kérése van vizsgálati adatainak módosítására, eltávolítására vagy frissítésére, kérjük, írjon a következő címre: register@clinicaltrials.gov. Amint a változás bevezetésre kerül a clinicaltrials.gov oldalon, ez a webhelyünkön is automatikusan frissül. .