ATI-450 Plus MTX vs. Placebo Plus MTX potilailla, joilla on kohtalainen tai vaikea aktiivinen RA
ATI-450 Plus MTX vs. Placebo Plus MTX potilailla, joilla on keskivaikea tai vaikea aktiivinen nivelreuma ja joilla on ollut riittämätön vaste pelkästään MTX:lle
This study evaluates ATI-450 plus MTX versus placebo plus MTX in participants with moderate to severe active RA who have had an inadequate response to MTX alone.
Tutkimuksen yleiskatsaus
Tila
Ehdot
Yksityiskohtainen kuvaus
This is a Phase 2b, randomized, multicenter, double-blind, parallel group, placebo controlled, dose ranging study to investigate the efficacy, safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of ATI-450 plus MTX versus placebo plus MTX in participants with moderate to severe active RA who have had an inadequate response to MTX alone.
Opintotyyppi
Ilmoittautuminen (Todellinen)
Vaihe
- Vaihe 2
Yhteystiedot ja paikat
Opiskelupaikat
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Pleven, Bulgaria, 5800
- Aclaris Investigational Site
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Plovdiv, Bulgaria, 4000
- Aclaris Investigational Site
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Plovdiv, Bulgaria, 4001
- Aclaris Investigational Site
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Plovdiv, Bulgaria, 4002
- Aclaris Investigational Site
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Plovdiv, Bulgaria, 4004
- Aclaris Investigational Site
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Sofia, Bulgaria, 1336
- Aclaris Investigational Site
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Sofia, Bulgaria, 1431
- Aclaris Investigational Site
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Sofia, Bulgaria, 1606
- Aclaris Investigational Site
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Varna, Bulgaria, 9000
- Aclaris Investigational Site
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Bialystok, Puola, 15-297
- Aclaris Investigational Site
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Bialystok, Puola, 15-879
- Aclaris Investigational Site
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Dąbrówka, Puola, 62-069
- Aclaris Investigational Site
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Krakow, Puola, 30-363
- Aclaris Investigational Site
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Lublin, Puola, 20-607
- Aclaris Investigational Site
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Nowa Sól, Puola, 67-100
- Aclaris Investigational Site
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Poznan, Puola, 60-218
- Aclaris Investigational Site
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Poznan, Puola, 60-446
- Aclaris Investigational Site
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Poznan, Puola, 61-397
- Aclaris Investigational Site
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Sochaczew, Puola, 96-500
- Aclaris Investigational Site
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Torun, Puola, 87-100
- Aclaris Investigational Site
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Warsaw, Puola, 04-141
- Aclaris Investigational Site
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Wroclaw, Puola, 52-442
- Aclaris Investigational Site
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Lesser Poland Voivodeship
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Krakow, Lesser Poland Voivodeship, Puola, 30-002
- Aclaris Investigational Site
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Lubelski
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Tomaszów Lubelski, Lubelski, Puola, 22-600
- Aclaris Investigational Site
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Lublin Voivodeship
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Lublin, Lublin Voivodeship, Puola, 20-362
- Aclaris Investigational Site
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Masovian Voivodeship
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Nadarzyn, Masovian Voivodeship, Puola, 05-830
- Aclaris Investigational Site
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Mzowieckie
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Grodzisk Mazowiecki, Mzowieckie, Puola, 05-825
- Aclaris Investigational Site
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Podlaskie Voivodeship
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Bialystok, Podlaskie Voivodeship, Puola, 15-351
- Aclaris Investigational Site
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Silesian Voivodeship
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Katowice, Silesian Voivodeship, Puola, 40-282
- Aclaris Investigational Site
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Warm.Maz.
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Elblag, Warm.Maz., Puola, 82-300
- Aclaris Investigational Site
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Warmińsko-Mazurskien
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Olsztyn, Warmińsko-Mazurskien, Puola, 10-117
- Aclaris Investigational Site
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Wielkopolska
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Poznan, Wielkopolska, Puola, 61-113
- Aclaris Investigational Site
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Brno, Tšekki, 615 00
- Aclaris Investigational Site
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Hlučín, Tšekki, 748 01
- Aclaris Investigational Site
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Ostrava, Tšekki, 702 00
- Aclaris Investigational Site
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Pardubice, Tšekki, 530 02
- Aclaris Investigational Site
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Prague, Tšekki, 128 50
- Aclaris Investigational Site
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Prague, Tšekki, 140 00
- Aclaris Investigational Site
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Uherské Hradiště, Tšekki, 686 01
- Aclaris Investigational Site
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California
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El Cajon, California, Yhdysvallat, 92020
- Aclaris Investigational Site
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Encino, California, Yhdysvallat, 91436
- Aclaris Investigational Site
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La Jolla, California, Yhdysvallat, 92093
- Aclaris Investigational Site
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Palm Desert, California, Yhdysvallat, 92260
- Aclaris Investigational Site
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Florida
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Tampa, Florida, Yhdysvallat, 33613
- Aclaris Investigational Site
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Oklahoma
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Oklahoma City, Oklahoma, Yhdysvallat, 73103
- Aclaris Investigational Site
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Pennsylvania
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Duncansville, Pennsylvania, Yhdysvallat, 16635
- Aclaris Investigational Site
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Tennessee
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Jackson, Tennessee, Yhdysvallat, 38305
- Aclaris Investigational Site
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Texas
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Cypress, Texas, Yhdysvallat, 77429
- Aclaris Investigational Site
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Mesquite, Texas, Yhdysvallat, 75150
- Aclaris Investigational Site
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San Antonio, Texas, Yhdysvallat, 78229
- Aclaris Investigational Site
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
Inclusion Criteria:
- Able to comprehend and be willing to sign the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved participant ICF prior to administration of any study-related procedures.
- Diagnosis of adult-onset RA as defined by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria.
- Have active moderate to severe RA at Screening.
- A minimum of 12 weeks on MTX with a stable MTX dose.
Exclusion Criteria:
- Current acute or chronic immunoinflammatory disease other than RA which may impact the course or assessment of RA.
- Uncontrolled non-immunoinflammatory disease that may place the participant at increased risk during the study or impact the interpretation of results (eg, previous malignancy, recurrent infection, previous venous thromboembolism).
- Participant has experience with > 2 biologics, > 1 JAK inhibitor, or a combination of 1 biologic experience and 1 JAK inhibitor.
- Currently receiving corticosteroids at doses > 10 mg/day of prednisone (or equivalent) or have been receiving an unstable dosing regimen of corticosteroids within 2 weeks of screening.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Satunnaistettu
- Inventiomalli: Rinnakkaistehtävä
- Naamiointi: Nelinkertaistaa
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
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Kokeellinen: ATI-450 20 mg BID plus Methotrexate
ATI-450 20 mg oral tablet twice daily (BID) with a stable weekly dose of methotrexate for 12 weeks |
15 mg to 25 mg weekly Oral, small molecule MK2 inhibitor
Muut nimet:
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Kokeellinen: ATI-450 50 mg BID plus Methotrexate
ATI-450 50 mg oral tablet BID with a stable weekly dose of methotrexate for 12 weeks |
15 mg to 25 mg weekly Oral, small molecule MK2 inhibitor
Muut nimet:
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Placebo Comparator: Placebo plus Methotrexate
Placebo oral tablet BID with a stable weekly dose of methotrexate for 12 weeks |
15 mg to 25 mg weekly Placebo tablet manufactured to match ATI-450 in appearance |
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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Percentage of Participants Achieving ACR20 at Week 12
Aikaikkuna: Week 12
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Participants achieving American College of Rheumatology (ACR) 20 (responders) were defined as having ≥20% improvement in both the number of swollen and tender joints (66/68 joint counts) and ≥20% improvement in ≥3 of the following 5 measures: Patient's Global Assessment of Disease Activity (VAS), Patient's Assessment of Arthritis Pain (VAS), Health Assessment Questionnaire-Disability Index (HAQ-DI), Physician's Global Assessment of Disease Activity (VAS), and acute phase reactant as measured by hsCRP. Model-based estimates and 95% confidence intervals (CIs) were produced. |
Week 12
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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
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ATI-450:n ja metaboliitin (CDD-2164) pitoisuudet
Aikaikkuna: 2 tuntia annoksen jälkeen päivinä 1, 8 ja 85
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2 tuntia annoksen jälkeen päivinä 1, 8 ja 85
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Percentage of Participants Achieving ACR50 at Week 12
Aikaikkuna: Week 12
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Participant achieving ACR50 (responders) were defined as having ≥50% improvement in both the number of swollen and tender joints (66/68 joint counts) and ≥50% improvement in ≥3 of the following 5 measures: Patient's Global Assessment of Disease Activity (VAS), Patient's Assessment of Arthritis Pain (VAS), HAQ-DI, Physician's Global Assessment of Disease Activity (VAS), Acute phase reactant as measured by hsCRP. Model-based estimates and 95% CIs were produced. |
Week 12
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Percentage of Participants Achieving ACR70 at Week 12
Aikaikkuna: Week 12
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Participants achieving ACR70 (responders) were defined as having ≥70% improvement in both the number of swollen and tender joints (66/68 joint counts) and ≥70% improvement in ≥3 of the following 5 measures: Patient's Global Assessment of Disease Activity (VAS), Patient's Assessment of Arthritis Pain (VAS), HAQ-DI, Physician's Global Assessment of Disease Activity (VAS), Acute phase reactant as measured by hsCRP. Model-based estimates and 95% CIs were produced. |
Week 12
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Change From Baseline in DAS28-CRP at Week 12
Aikaikkuna: Baseline, Week 12
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The DAS28-CRP consists of a composite score of the following variables: TJC28, SJC28, CRP (hsCRP was used for the purposes of this study), and Patient's Global Assessment of Disease Activity. Interpretation of the DAS28-CRP is on a scale of 0 to 9.4, where <2.6 is considered remission, ≥2.6 to <3.2 is considered low/minimal disease activity, ≥3.2 to ≤5.1 is considered moderate disease activity, and >5.1 is considered high/severe disease activity. The least square (LS) mean change from baseline in DAS28-CRP at Week 12 was estimated from the Mixed Model Repeated Measures (MMRM) model. |
Baseline, Week 12
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Percentage of Participants Achieving DAS28-CRP Remission (Score <2.6) at Week 12
Aikaikkuna: Week 12
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The Disease Activity Score using 28 Joint Count-C-reactive protein (DAS28-CRP) consists of a composite score of the following variables: TJC28, SJC28, CRP (hsCRP is used for the purposes of this study), and Patient's Global Assessment of Disease Activity. Interpretation of the DAS28-CRP is on a scale of 0 to 9.4, where <2.6 is considered remission, ≥2.6 to <3.2 is considered low/minimal disease activity, ≥3.2 to ≤5.1 is considered moderate disease activity, and >5.1 is considered high/severe disease activity. Model-based estimates and 95% CIs were produced. |
Week 12
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Percentage of Participants Achieving DAS28-CRP Low Disease Activity (Score ≤ 3.2) at Week 12
Aikaikkuna: Week 12
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The DAS28-CRP consists of a composite score of the following variables: TJC28, SJC28, CRP (hsCRP is used for the purposes of this study), and Patient's Global Assessment of Disease Activity. Interpretation of the DAS28-CRP is on a scale of 0 to 9.4, where <2.6 is considered remission, ≥2.6 to <3.2 is considered low/minimal disease activity, ≥3.2 to ≤5.1 is considered moderate disease activity, and >5.1 is considered high/severe disease activity. Model-based estimates and 95% CIs were produced. |
Week 12
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Change From Baseline in HAQ-DI Score at Week12
Aikaikkuna: Baseline, Week 12
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The HAQ-DI (standard disability method calculation) was utilized to assess the participant's physical function or disability according to the participant. The HAQ-DI is a 20-item, validated questionnaire used to assess the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities [errands and chores]). Responses in each functional area are scored from 0 (no difficulty) to 3 (inability to perform a ask in that area). Overall score was computed as the sum of category scores and divided by the number of categories answered, ranging from 0 to 3. A lower score demonstrated less disability. LS mean change from baseline in HAQ-DI score at Week 12 was estimated from the MMRM model. |
Baseline, Week 12
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Change From Baseline in CDAI Score at Week 12
Aikaikkuna: Baseline, Week 12
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The Clinical Disease Activity Index (CDAI) was the sum of 4 outcome parameters:
Interpretation of the CDAI disease activity was measured on a scale of 0 to 76, where ≤2.8 was considered remission, >2.8 to ≤10 was considered low/minimal disease activity, >10 to ≤22 was considered moderate disease activity, and >22.0 was considered high/severe disease activity. LS mean change from baseline in CDAI score at Week 12 was estimated from the MMRM model. |
Baseline, Week 12
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Percentage of Participants Achieving CDAI Remission (Score ≤ 2.8)
Aikaikkuna: Week 12
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The CDAI was the sum of 4 outcome parameters:
Interpretation of the CDAI disease activity was measured on a scale of 0 to 76, where ≤2.8 was considered remission, >2.8 to ≤10 was considered low/minimal disease activity, >10 to ≤22 was considered moderate disease activity, and >22.0 was considered high/severe disease activity. Model-based estimates and 95% CIs were produced. |
Week 12
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Percent Change From Baseline in hsCRP Level at Week 12
Aikaikkuna: Baseline, Week 12
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Blood samples were evaluated to measure levels of hsCRP. |
Baseline, Week 12
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Change From Baseline in Short Form Health Survey SF-36 Physical Component Summary (PCS) Score at Week 12
Aikaikkuna: Baseline, Week 12
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The PCS is composed of 4 scales of the Short Form-36 Health Status Survey Questionnaire (SF-36) version 2 assessing physical function, role limitations caused by physical problems, bodily pain, and general health. The range of the SF-36 PCS is between 0 and 100, where higher scores represent better physical functioning. A 2.5 to 5-point change from baseline is established as the minimum clinically-important difference for the PCS in RA participants. LS mean change from baseline in SF-36 PCS score at Week 12 was estimated from the MMRM model. |
Baseline, Week 12
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Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue Scale (FACIT-Fatigue) Score at Week 12
Aikaikkuna: Baseline, Week 12
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The FACIT-Fatigue is a 13-item questionnaire that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a 4 point Likert scale (4 = not at all fatigued to 0 = very much fatigued). The total score range is from 0 to 52. The higher the score, the lower the fatigue level. LS mean change from baseline in FACIT-Fatigue score at Week 12 was estimated from the MMRM model. |
Baseline, Week 12
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Yhteistyökumppanit ja tutkijat
Sponsori
Tutkijat
- Opintojohtaja: Ajay Aggarwal, Aclaris Therapeutics, Inc.
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Ensisijainen valmistuminen (Todellinen)
Opintojen valmistuminen (Todellinen)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Todellinen)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
Muita asiaankuuluvia MeSH-ehtoja
- Tuki- ja liikuntaelinten sairaudet
- Nivelsairaudet
- Reumaattiset sairaudet
- Sidekudostaudit
- Autoimmuunisairaudet
- Immuunijärjestelmän sairaudet
- Iho- ja sidekudostaudit
- Niveltulehdus
- Niveltulehdus, nivelreuma
- Heterosykliset yhdisteet
- Heterosykliset yhdisteet, 2-rengas
- Heterosykliset yhdisteet, sulatettu rengas
- Pterinit
- Pteridiinit
- Aminopteriini
- Metotreksaatti
Muut tutkimustunnusnumerot
- ATI-450-RA-202
- 2021-002860-31 (EudraCT-numero)
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