A Phase 2 Long-Term Extension Study in Rheumatoid Arthritis Treated Patients Previously Treated in a Preceding Study with ABBV-105 Given Alone or in Combination with Upadacitinib.

• Register: EUCTR
• Last refreshed on: 5 January 2021
• Main ID: EUCTR2018-002306-31-ES
• Date of registration: 12/04/2019
• Prospective Registration: No
• Primary sponsor: AbbVie Deutschland GmbH & Co. KG
• Public title: A Phase 2 Long-Term Extension Study in Rheumatoid Arthritis Treated Patients Previously Treated in a Preceding Study with ABBV-105 Given Alone or in Combination with Upadacitinib.
• Scientific 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)
• Date of first enrolment: 04/04/2019
• Target sample size: 120
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2018-002306-31
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: Treatments continue from M16-063, except those initially assigned placebo (switching to ABBV-599). If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 5
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, Czech Republic, Germany, Hungary, Poland, Spain, United Kingdom

Contacts

• Name: EU Clinical Trials Helpdesk
• Affiliation: AbbVie Ltd.

• Name: EU Clinical Trials Helpdesk
• Affiliation: AbbVie Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
Adult male or female, at least 18 years old.

Diagnosis of RA for = 3 months based on the 2010 ACR/EULAR classification criteria for RA.

Females must not be pregnant, breastfeeding, or considering becoming pregnant during the study or for approximately 30 days after the last dose of study drug.

For all females of child-bearing potential: a negative serum pregnancy test at the Screening Visit and a negative urine pregnancy test at baseline prior to the first dose of study drug in the M16-063 study as well as persistently negative urine pregnancy test throughout M16-063 and at entrance into this study.

Female subjects of childbearing potential must practice at least 1 protocol-specified method of birth control that is effective from Study Day 1 through at least 30 days. If required per local practices, male or female condom with or without spermicide OR cap, diaphragm or sponge with spermicide should be used in addition to one of the highly effective protocol-specified birth control methods (excluding true abstinence). A condom is required in the following countries: UK, Germany and Spain. Female subjects of non-childbearing potential do not need to use birth control.

Subjects must have been treated for = 3 months with = 1 bDMARD therapy but continue to exhibit active RA or had to discontinue due to intolerability or toxicity, irrespective of treatment duration.

Subjects must have been receiving csDMARD therapy = 3 months prior to M16-063 baseline visit. The following csDMARDs are allowed: oral or parenteral methotrexate (MTX) (7.5 to 25 mg/week), sulfasalazine (= 3000 mg/day), hydroxychloroquine (= 400 mg/day), chloroquine (= 250 mg/day), and leflunomide (= 20 mg/day). A combination of up to two background csDMARDs is allowed EXCEPT the combination of MTX and leflunomide.

Subjects must have discontinued all bDMARDs prior to the first dose of study drug. The washout period for bDMARDs prior to the first dose of study drug is specified below or should be at least five times the mean terminal elimination half-life of a drug:

- = 4 weeks for etanercept;
- = 10 weeks for adalimumab, infliximab, certolizumab, golimumab, tocilizumab, and abatacept;
- = 1 year for rituximab OR = 6 months if B cells have returned to pretreatment level or normal reference range (central lab) if pretreatment levels are not available.

Subjects must have discontinued all high-potency opiates at least 1 week and oral traditional Chinese medicine for at least 4 weeks prior to the first dose of study.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10

Exclusion criteria:
Laboratory values not meeting toxicity management criteria from the M16-063 study

History of any of the following cardiovascular conditions:

-Moderate to severe congestive heart failure (New York Heart Association Class III or IV).
-Recent history (within past 6 months) of cerebrovascular accident (CVA), myocardial infarction, and/or coronary stenting.
-Uncontrolled hypertension as defined by a persistent systolic blood pressure (BP) > 160 mmHg or diastolic BP > 100 mmHg. For subjects with known hypertension, the subject's BP must be stable for at least 4 weeks on current, stable anti-hypertensive medications.
-Prior unprovoked deep vein thrombosis (DVT) or pulmonary embolism (PE) (i.e., any spontaneous event not directly attributable to trauma or vascular instrumentation).
-Any other condition which, in the opinion of the Investigator, would put the subject at risk by participating in the protocol.

Arthritis with onset prior to age 17 years or current diagnosis of inflammatory joint disease other than RA (including but not limited to gout, systemic lupus erythematosus, psoriatic arthritis, axial spondyloarthritis including ankylosing spondylitis and non-radiographic axial spondyloarthritis, reactive arthritis, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis, fibromyalgia [currently with active symptoms], or any arthritis with onset prior to age 17 years). Current diagnosis of secondary Sjogren's Syndrome is permitted.

Must not have been treated with any investigational drug, other than those supplied in M16-063, within 30 days or five half-lives of the drug (whichever is longer) prior to the first dose of study drug or is currently enrolled in another clinical study, other than M16-063.

Must not have any active or recurrent viral infection that, based on the Investigator's clinical assessment, makes the subject an unsuitable candidate for the study, including hepatitis B virus (HBV) or hepatitis C virus (HCV), recurrent or disseminated (even a single episode) herpes zoster, disseminated (even a single episode) herpes simplex, or HIV.

Active HBV, HCV, and HIV are defined as:
- HBV: Hepatitis B surface antigen (HBs Ag) positive (+) or, for hepatitis B core antibody (HBc Ab) positive subjects, detection of HBV DNA by polymerase chain reaction (PCR);
- HCV: HCV RNA detectable in any subject with anti-HCV antibody (HCV Ab);
- HIV: Confirmed positive anti-HIV antibody (HIV Ab) test.

Have active TB or meets TB exclusionary parameters (defined as the presence of active TB or latent TB not adequately treated as per protocol requirements).

Have used known strong cytochrome P450 (CYP)3A or CYP1A2 inhibitors or strong CYP3A or CYP1A2 inducers from Screening through the end of the study.

Receipt of any live vaccine within 4 weeks prior to the first dose of study drug, or expected need of live vaccination during study participation including at least 4 weeks after the last dose of oral study drug.

History of any malignancy except for successfully treated non-melanoma skin cancer (NMSC) or localized carcinoma in situ of the cervix.

History of clinically significant (per Investigator's judgment) drug or alcohol abuse within the last 6 months.
History of gastrointestinal perforation (other than appendicitis or penetrating injury), diverticulitis or significantly increased risk for gastrointestinal perforation per investigator judgment.

Any conditions that could interfere with drug absorption including b

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rheumatoid Arthritis
MedDRA version: 20.0 Level: HLT Classification code 10039075 Term: Rheumatoid arthritis and associated conditions System Organ Class: 100000004870

Therapeutic area: Body processes [G] - Immune system processes [G12]

Intervention(s)

Product Code: ABBV-105
Pharmaceutical Form: Capsule
INN or Proposed INN: ABBV-105
CAS Number: 1643570-24-4
Current Sponsor code: ABBV-105
Other descriptive name: ABBV-105
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Code: ABBV-105
Pharmaceutical Form: Capsule
INN or Proposed INN: ABBV-105
CAS Number: 1643570-24-4
Current Sponsor code: ABBV-105
Other descriptive name: ABBV-105
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Capsule
Route of administration of the placebo: Oral use

Product Name: Upadacitinib
Product Code: ABT-494
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Upadacitinib
CAS Number: 1310726-60-3
Current Sponsor code: ABT-494
Other descriptive name: ABT-494
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Change in disease activity score (DAS)28 (C-reactive protein [CRP]) from baseline of Study M16-063.

Secondary Objective: n/a

Main Objective: The primary objective of this study is to evaluate the long-term safety, tolerability, and efficacy of ABBV-105 and ABBV-599 in RA subjects who have completed Study M16-063.

Timepoint(s) of evaluation of this end point: Week 12/Baseline, Week 18, Week 24, Week 30, Week 36, Week 48, Week 60/Premature Discontinuation.

Secondary Outcome(s)

Secondary end point(s): Proportion of subjects achieving DAS Low Disease Activity (LDA), defined as DAS28 CRP =3.2;
Proportion of subjects achieving DAS Clinical Remission (CR), defined as DAS28 CRP < 2.6;
Proportion of subjects achieving American College of Rheumatology (ACR) 20/50/70 response.

Timepoint(s) of evaluation of this end point: Week 12/Baseline, Week 18, Week 24, Week 30, Week 36, Week 48, Week 60/Premature Discontinuation.

Secondary ID(s)

M16-763

2018-002306-31-BE

Source(s) of Monetary Support

AbbVie INC

Ethics review

Status: Approved
Approval date: 20/03/2019
Contact: