PrimaryThe primary objective is to evaluate the effect of ABT-981 on pain using the Australian/Canadian Osteoarthritis Hand Index (AUSCAN NR3.1) pain subdomain score, in subjects with erosive hand OA at Week 16.Secundary* Evaluate the safety and…
ID
Source
Brief title
Condition
- Joint disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy measurement will be the change of pain from Baseline to 16
weeks as assessed by the AUSCAN NR3.1 pain subdomain score.
Secondary outcome
* Change of total AUSCAN score and individual subdomain (pain, physical
function and stiffness) scores from Baseline using the AUSCAN NR3.1.
* Change of subject index hand resting pain from Baseline using NRS-11 score.
* Change of patient global assessment of arthritis from Baseline using NRS-11
score.
Background summary
Osteoarthritis (OA) is a joint disorder that involves degeneration of articular
cartilage, inflammation of the entire joint as manifested by synovitis, and
changes in the subchondral bone. OA is the most common form of arthritis and
the number one cause of workforce disability.
The importance of inflammatory elements in OA is increasingly recognized; the
role of cytokines and chemokines as the "inflammatory"
mediators that cause inflamed synovial tissue and cartilage in OA have been
extensively studied.
Among these inflammatory mediators, Interleukin-1 (IL-1) is identified as the
key factor in cartilage and synovium tissue signaling pathways. IL-1 has long
been known as the most potent catabolic cytokine and is thought to play a major
role in the development and progression of OA both in terms of disease
(structural progression) and symptoms (pain and functional deterioration).
IL-1α and IL-1β are 2 structurally distinct cytokines that bind to the IL-1
receptor complex. Both induce structural changes, such as cartilage
degradation, bone sclerosis and synovial proliferation, by inducing proteases
and proinflammatory cytokines in joints and have also been shown to play a role
in OA pain.
ABT-981 is a novel biologic drug candidate targeting IL-1α and IL-1β.
Study objective
Primary
The primary objective is to evaluate the effect of ABT-981 on pain using the
Australian/Canadian Osteoarthritis Hand Index (AUSCAN NR3.1) pain subdomain
score, in subjects with erosive hand OA at Week 16.
Secundary
* Evaluate the safety and tolerability of ABT-981 in subjects with erosive hand
OA throughout the study.
* Evaluate the effect of ABT-981 on AUSCAN NR3.1 total and individual subdomain
(pain, physical function and stiffness) scores of erosive hand OA throughout
the study.
* Evaluate the effect of ABT-981 on Subject Assessment of Hand Pain Intensity
via an 11-point Numeric Rating Scale (NRS-11) throughout the study.
* Evaluate the effect of ABT-981 on Patient Global Assessment (PGA) of Hand
Osteoarthritis Status using a NRS-11 throughout the study.
* Evaluate the PK and ADA levels of ABT-981.
Study design
This is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled,
parallel group study designed to evaluate the safety, tolerability, efficacy,
PK and pharmacodynamics (PD) of ABT-981 compared to placebo in subjects with
erosive hand OA.
Approximately 120 subjects meeting the selection criteria will be randomized
into the study at approximately 45 sites.
The duration of the study and subject participation will be approximately 32
weeks. The study consists of 2 periods: 1) a Screening and Washout Period for
approximately 45 days prior to first dose; 2) a 26-Week Study Period.
Intervention
Approximately 120 patients meeting all of the inclusion criteria and none of
the exclusion criteria during Screening (within 45 days prior to the first dose
of study drug) will be enrolled. Patients taking analgesics must complete a
Washout Period and discontinue all analgesic medications for at least 5
half-lives of the longest acting analgesic used, or 48 hours, whichever is
longer, prior to the first dose of study drug. Upon completion of the wash-out
period, the baseline MRI should be performed 7 - 17 days prior to Day 1. During
the Washout Period through Week 26 it is permitted to take acetaminophen as
rescue mediation, but not within 48 hours prior to MRIs and visits with
questionnaires.
Patients will be randomized to one of the two treatment groups to receive
either placebo or 200 mg ABT-981 every other week for 26 weeks (treatment
period).
Patients will undergo 2 X-rays and 2 MRIs during the study.
Study burden and risks
The risks associated with this study are linked together with the possible side
effects of the investigational product. The burden of the subject will continue
to work with the study procedures, visits, and venapunctions. All subjects will
be closely monitored and supervised by experienced doctors and study staff for
possible side effects.
Wegalaan 9
Hoofddorp 2132JD
NL
Wegalaan 9
Hoofddorp 2132JD
NL
Listed location countries
Age
Inclusion criteria
1. Male or female between the ages of 35 to 80 years (inclusive) at the time of signing the informed consent.
2. Subject must fulfill 1990 American College of Rheumatology (ACR) hand OA criteria, defined as
hand pain, aching, or stiffness and three or four of the following features:
* hard tissue enlargement of two or more of the following 10 selected joints: the second and
third distal interphalangeal (DIP) joint of both hands, the second and third proximal
interphalangeal (PIP) joints of both hands, the first carpometacarpal (CMC) joints of both hands,
* hard tissue enlargement of two or more DIP joints,
* fewer than three swollen metacarpophalangeal (MCP) joints, and
* deformity of at least one of the 10 selected joints.
3. Subject must have radiographic evidence of erosive hand OA with evidence of an "E" (erosive) or "E/R" (erosive with remodeling) joint as defined by Verbruggen and colleagues in at least one of the hand interphalangeal joints based on hand x-rays obtained during the Screening Period or within 3 months of the Screening Visit (a qualified central reader will perform the eligibility reading
according to a pre-defined criterion).
4. Subject has one or more clinical signs and symptoms of active inflammation in at least three hand joints, with active inflammation defined as localized tenderness and/or soft tissue swelling at Screening and Day 1 Visit.
5. Subject Assessment of Hand Pain Intensity in at least one hand is >= 6 (11-point Numeric Rating
Scale [NRS-11]) at Screening and Day 1 Visit.
6. Patient Global Assessment of Arthritis Status is >= 6 (NRS-11) at Screening and Day 1 Visit.
Exclusion criteria
1. Previous exposure to any anti-IL-1 treatment including (and not limited to) anakinra, canakinumab and rilonacept OR one or more of the following:
* Oral, intramuscular (IM), intravenous (IV), epidural or intra-articular corticosteroids within 1 month prior to Screening,
* Intra-articular hyaluronic acid injection into hand joint(s) within 6 months prior to Screening,
* Any investigational drug product of chemical or biologic nature within 1 month or 5 half-lives
of the drug (whichever is longer) prior to the first dose of study drug,
Any immunosuppressive biologic therapy including (and not limited to), etanercept,
adalimumab, infliximab, golimumab, certolizumab, abatacept, tocilizumab, natalizumab,
efalizumab, ustekinumab, belimumab or rituximab within 1 month or 5 half-lives (whichever is
longer) prior to the first dose of study drug,
* Current use of immunosuppressive oral medications including (and not limited to) Tofacitinib,
hydroxychloroquine, azathioprine, methotrexate, leflunomide, mycophenolate, sulfasalazine,
gold, cyclophosphamide, penicillamine and/or tacrolimus, or tetracycline based agents within
3 months or 5 half-lives (whichever is longer) prior to the first dose of study drug,
* Colchicine within 1 month prior to the first dose of study drug,
* Vaccination with a live viral agent (including live attenuated influenza vaccine via nasal spray)
<= 30 day prior to Screening Visit through 10 weeks (5 × the half-life of ABT-981) after the last
dose of study drug.
2. Absolute neutrophil count (ANC) < 2,000/mm3 at Screening.
3. Diagnosis of one or more of the following:
* Fibromyalgia,
* Inflammatory arthritis such as rheumatoid arthritis, peripheral seronegative
spondyloarthropathy,
* Psoriatic arthritis, evidence of psoriasis,
* Microcrystalline (including gout and pseudo gout) arthritis affecting the hands,
* Any OA of the hands due to an infectious origin or acute traumatic episode,
* Secondary OA due to (but not limited to) hemochromatosis, alkaptonuria, Wilson's disease,
acromegaly and/or hyperparathyroidism,
* OA linked to cartilage and bone dysplasia,
* Other chronic painful syndromes that could interfere with assessment of pain at the hand(s).
4. Any uncontrolled medical illness or an unstable treatment or therapy.
5. Clinically significant cardiac disease (including MI, coronary stenting or CVA) within last 12 months of Study Day 1 or clinically significant findings at Screening ECG including QT interval corrected for heart rate by Fridericia's formula (QTcF) > 470 msec in females or > 450 msec in males or PR interval > 220 msec.
6. Evidence of dysplasia or history of malignancy (including lymphoma and leukemia) within the past
5 years other than a successfully treated non-metastatic cutaneous squamous cell or basal cell
carcinoma or localized carcinoma in situ of the cervix.
7. History of persistent chronic or active infection(s) requiring hospitalization or treatment with
antimicrobials/antibiotics (intravenous, oral, or injection) within 1 month prior to the first dose of
study drug.
8. Any reason that prohibits a subject to undergo an MRI (e.g., pacemaker, certain types of metal
implants, etc.). The number of subjects not undergoing an MRI will be limited to 10 per arm
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2014-001096-31-NL |
| CCMO | NL51904.058.15 |