A Study in Rheumatoid Arthritis Patients Who Have Completed a Preceding Study With ABBV-105 Given Alone or in Combination With Upadacitinib

Rheumatoid Arthritis (RA) Clinical Trial

Official title:

A Phase 2, Multicenter, Double-Blind, Parallel Group Long Term Extension Study in Rheumatoid Arthritis Subjects Who Have Completed a Preceding Phase 2 Randomized Controlled Trial With ABBV-105 Given Alone or in Combination With Upadacitinib (ABBV-599)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03823378
• Other study ID #: M16-763
• Secondary ID: 2018-002306-31
• Status: Terminated
• Phase: Phase 2
• Start date: May 13, 2019
• Est. completion date: September 9, 2020

Study information

• Verified date: August 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This was a long-term extension (LTE) study to assess the safety, tolerability, and efficacy of ABBV-105 (elsubrutinib [ELS]) and ABBV-599 (ELS 60 mg and upadacitinib [UPA] 15 mg) in participants with rheumatoid arthritis (RA) who completed Study M16-063 (NCT03682705).

Description:

This was a Phase 2, double-blind, multicenter, long-term extension (LTE) study to assess the safety, tolerability, and efficacy of 3 doses of ABBV-105 (elsubrutinib [ELS] 5 mg, 20 mg, and 60 mg) and ABBV-599 (ELS 60 mg and upadacitinib [UPA] 15 mg) in adults with active rheumatoid arthritis with inadequate response or intolerance to biologic disease-modifying antirheumatic drugs (bDMARDs). Participants who successfully completed treatment in the feeder Study M16-063, a Phase 2 dose exploratory study, were eligible to participate in this study. Those who met eligibility criteria and entered this study receiving ELS, ABBV-599, or UPA from Study M16-063 continued on their previously assigned treatment through termination of this study. Participants originally randomized to placebo in Study M16-063 rolled over to ABBV-599 in a blinded fashion in this study.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 97
• Est. completion date: September 9, 2020
• Est. primary completion date: September 9, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Participant has completed Study M16-063
• Participant has not developed any laboratory or clinical discontinuation criteria as defined in the Study M16-063 protocol
• Participant is willing and/or able to comply with procedures required in the current study protocol

Exclusion Criteria:

• Participant is currently enrolled or planning to enroll in another interventional clinical study while participating in this study (except the preceding study M16-063)
• Participant requires vaccination with any live vaccine during study participation, including at least 30 days after the last dose of study drug

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis (RA)

Intervention

Drug:
• Elsubrutinib
Elsubrutinib capsule will be administered orally.
• Upadacitinib
Upadacitinib tablet will be administered orally.
• Placebo for elsubrutinib
Placebo capsule for elsubrutinib will be administered orally.
• Placebo for upadacitinib
Upadacitinib placebo tablet will be administered orally.

Locations

Country	Name	City	State
Belgium	UZ Leuven /ID# 207722	Leuven
Belgium	Cliniques Universitaires Saint Luc /ID# 207719	Woluwe-Saint-Lambert	Bruxelles-Capitale
Canada	Rheumatology Research Assoc /ID# 207769	Edmonton	Alberta
Canada	Dr. Latha Naik /ID# 213440	Saskatoon	Saskatchewan
Canada	Mount Sinai Hosp.-Toronto /ID# 206851	Toronto	Ontario
Canada	CIADS Research Co Ltd /ID# 206853	Winnipeg	Manitoba
Canada	Manitoba Clinic /ID# 206852	Winnipeg	Manitoba
Czechia	Revmatolog s.r.o. /ID# 209941	Jihlava 1	Jihlava
Czechia	Revmatologie MUDr. Klara Sirova /ID# 209944	Ostrava
Czechia	CCR Czech a.s /ID# 209942	Pardubice
Czechia	Revmatologicky ustav Praha /ID# 209943	Prague 2	Praha 2
Hungary	Revita Reumatologiai Rendelo /ID# 208187	Budapest
Hungary	CRU Hungary Egeszsegugyi és Szolgaltato Kft. /ID# 208186	Miskolc	Borsod-Abauj-Zemplen
Hungary	Szabolcs-Szatmar-Bereg Megyei Korhazak & Egyetemi Oktatokorhaz /ID# 208184	Nyíregyháza	Szabolcs-Szatmar-Bereg
Hungary	CMED Rehabilitacios es Diagnosztikai Kozpont /ID# 208188	Szekesfehervar
Hungary	Vital Medical Center Orvosi-es Fogaszati Kozpont /ID# 208185	Veszprem
Poland	ClinicMed Daniluk, Nowak Sp.j. /ID# 212578	Bialystok	Podlaskie
Poland	Malopolskie Centrum Kliniczne /ID# 209902	Cracow	Malopolskie
Poland	McBk Sc /Id# 212577	Grodzisk Mazowiecki	Mazowieckie
Poland	NBR Polska /ID# 209904	Warsaw	Mazowieckie
Poland	Reumatika - Centrum Reumatologii NZOZ /ID# 209903	Warsaw
Spain	Hospital Universitario A Coruña - CHUAC /ID# 207732	A Coruña	A Coruna
Spain	Hospital Clinic /ID# 207740	Barcelona
Spain	Hospital Universitario Basurto /ID# 207737	Bilbao
Spain	Hospital Universitario Virgen de las Nieves /ID# 209975	Granada
Spain	Hospital Clinico Universitario San Carlos /ID# 207738	Madrid
Spain	Hospital Regional de Malaga /ID# 207735	Málaga	Malaga
Spain	Hospital Unversitario Marques de Valdecilla /ID# 207729	Santander	Cantabria
Spain	Hospital Universitario y Politecnico La Fe /ID# 207739	Valencia
United Kingdom	University of Oxford /ID# 210571	Oxford

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

Belgium,  Canada,  Czechia,  Hungary,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events (AEs)	An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug as either having a reasonable possibility or no reasonable possibility. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after the first dose of study drug.	On or after the first dose of study drug in Study M16-763, and up to 30 days after the last dose of study drug in Study M16-763, up to 52 weeks
Secondary	Change in Disease Activity Score 28 C-reactive Protein (DAS28-CRP) From Baseline of Study M16-063 at Each Study Visit in Study M16-763	The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from Baseline indicates improvement in disease activity.	Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763
Secondary	Percentage of Participants Achieving Low Disease Activity (LDA) Based on Disease Activity Score 28 C-reactive Protein (DAS28-CRP)	The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Low Disease Activity (LDA) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than or equal to 3.2.	Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763
Secondary	Percentage of Participants Achieving Clinical Remission (CR) Based on Disease Activity Score 28 C-reactive Protein (DAS28-CRP)	The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. Clinical Remission (CR) based on DAS28 (CRP) is defined as achieving a DAS28 (CRP) of less than 2.6.	Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763
Secondary	Change in Clinical Disease Activity Index (CDAI) From Baseline of Study M16-063	The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. A negative change from Baseline indicates improvement in disease activity.	Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763
Secondary	Percentage of Participants Achieving Low Disease Activity (LDA) Based on Clinical Disease Activity Index (CDAI) Criteria	The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. Low Disease Activity (LDA) based on CDAI is defined as achieving a total CDAI score of less than or equal to 10.	Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763
Secondary	Percentage of Participants Achieving Clinical Remission (CR) Based on Clinical Disease Activity Index (CDAI) Criteria	The CDAI is a composite index for assessing disease activity based on the summation of the total tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), patient global assessment of disease activity measured on a VAS from 0 to 10 cm, and physician global assessment of disease activity measured on a VAS from 0 to 10 cm. The total CDAI score ranges from 0 to 78 with higher scores indicating higher disease activity. Complete Remission (CR) based on CDAI is defined as achieving a total CDAI score of less than or equal to 2.8.	Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763
Secondary	Percentage of Participants With an American College of Rheumatology 20% (ACR20) Response	Participants who met the following 3 conditions for improvement from baseline of Study M16-063 were classified as meeting the American College of Rheumatology 20% response (ACR20) criteria: = 20% improvement in 68-tender joint count from Baseline of Study M16-063; = 20% improvement in 66-swollen joint count from Baseline of Study M16-063 and; = 20% improvement in at least 3 of the 5 following parameters from Baseline of Study M16-063: Patient's Assessment of Pain (Visual Analog Scale [VAS]); Patient's Global Assessment of Disease Activity (PtGA); Physician's Global Assessment of Disease Activity (PhGA); Health Assessment Questionnaire Disability Index (HAQ-DI); High-sensitivity C-reactive protein (hsCRP)	Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763
Secondary	Percentage of Participants With an American College of Rheumatology 50% (ACR50) Response	Participants who met the following 3 conditions for improvement from baseline of Study M16-063 were classified as meeting the American College of Rheumatology 50% response (ACR50) criteria: = 50% improvement in 68-tender joint count from Baseline of Study M16-063; = 50% improvement in 66-swollen joint count from Baseline of Study M16-063 and; = 50% improvement in at least 3 of the 5 following parameters from Baseline of Study M16-063: Patient's Assessment of Pain (Visual Analog Scale [VAS]); Patient's Global Assessment of Disease Activity (PtGA); Physician's Global Assessment of Disease Activity (PhGA); Health Assessment Questionnaire Disability Index (HAQ-DI); High-sensitivity C-reactive protein (hsCRP)	Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763
Secondary	Percentage of Participants With an American College of Rheumatology 70% (ACR70) Response	Participants who met the following 3 conditions for improvement from baseline of Study M16-063 were classified as meeting the American College of Rheumatology 70% response (ACR70) criteria: = 70% improvement in 68-tender joint count from Baseline of Study M16-063; = 70% improvement in 66-swollen joint count from Baseline of Study M16-063 and; = 70% improvement in at least 3 of the 5 following parameters from Baseline of Study M16-063: Patient's Assessment of Pain (Visual Analog Scale [VAS]); Patient's Global Assessment of Disease Activity (PtGA); Physician's Global Assessment of Disease Activity (PhGA); Health Assessment Questionnaire Disability Index (HAQ-DI); High-sensitivity C-reactive protein (hsCRP)	Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763
Secondary	Change in Swollen Joint Count 66 (SJC66) From Baseline of Study M16-063	Sixty-six joints were assessed for swelling by physical examination. Swelling of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with swelling) to 66 (worst possible score/66 joints with swelling). Negative values indicate improvement from baseline.	Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763
Secondary	Change in Tender Joint Count 68 (TJC68) From Baseline of Study M16-063	Sixty-eight joints were assessed for tenderness by physical examination. Pain or tenderness of each joint was classified as present (1) or absent (0), for a total possible score of 0 (0 joints with tenderness) to 68 (worst possible score/68 joints with tenderness). Negative values indicate improvement from baseline.	Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763
Secondary	Change in Participant's Assessment of Pain (Visual Analog Scale [VAS]) From Baseline of Study M16-063	Participants rated their pain on a visual analogue scale (VAS) of 0 to 100 (mm), with 0 representing no pain and 100 representing the worst possible pain. Negative values indicate improvement from baseline.	Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763
Secondary	Change in Patient's Global Assessment of Disease Activity (PtGA) From Baseline of Study M16-063	Participants rated their disease activity for the past 24 hours using a Patient's Global Assessment of Disease Activity Global visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline.	Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763
Secondary	Change in Physician's Global Assessment of Disease Activity (PhGA) From Baseline of Study M16-063	The physician assessed a participant's disease activity at the time of the visit using a Physician's Global Assessment of Disease visual analogue scale (VAS). The range is 0 to 100 mm, with 0 representing no disease activity and 100 representing severe disease activity. Negative values indicate improvement from baseline.	Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763
Secondary	Change in Health Assessment Questionnaire Disability Index (HAQ-DI) From Baseline of Study M16-063	The Health Assessment Questionnaire - Disability Index is a patient-reported questionnaire that measures the degree of difficulty a person has in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and errands and chores) over the past week. Participants assessed their ability to do each task on a scale from 0 (without any difficulty) to 3 (unable to do). Scores were averaged to provide an overall score ranging from 0 to 3, where 0 represents no disability and 3 represents very severe, high-dependency disability. A negative change from baseline in the overall score indicates improvement.	Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763
Secondary	Change in High-Sensitivity C-Reactive Protein (Hs-CRP) From Baseline of Study M16-063	C-reactive protein is a blood test marker for inflammation in the body, and levels rise in response to inflammation. A negative change from baseline indicates improvement.	Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763
Secondary	Change in Morning Stiffness Severity From Baseline of Study M16-063	Morning stiffness severity was assessed by a numeric rating-scale (NRS). Participants rated the severity of morning stiffness during the past week from 0 to 10 with 0 representing "not severe" and 10 "very severe". Negative values indicate improvement from baseline.	Baseline in Study M16-063, Weeks 18, 24, 30, 36, 48, and 60 in Study M16-763

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