Adhesive CapsulitisPhase 2ACNCT02006719
Clinical Study for the Treatment of Adhesive Capsulitis of the Shoulder
A Phase 2 study testing Collagenase Clostridium Histolyticum in people with Adhesive Capsulitis and Frozen Shoulder, run by Endo USA Inc., a Keenova Therapeutics Company at 46 sites in 2 countries.
Trial summary
The objectives of this study are to assess the safety, effectiveness, and immunogenicity of AA4500 in the treatment of adhesive capsulitis. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adhesive Capsulitis, Frozen Shoulder
- What is being tested?
- Collagenase Clostridium Histolyticum
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 322 participants
- Where
- 46 sitesin 2 countries
- Study dates
- Nov 2013to Dec 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Unilateral idiopathic adhesive capsulitis of one shoulder for at least 3 months but not more than 12 months (Frozen Stage)
- Normal range of motion in the contralateral shoulder
- Restricted active range of motion (AROM) in the affected shoulder defined as: a deficit of at least 60 degrees in total AROM in the affected shoulder as compared with the total AROM in the contralateral shoulder and a deficit of at least 30 degrees in AROM in at least one of the following planes as compared with the contralateral shoulder:
- Forward flexion
- Abduction
- External rotation with the elbow up to 90 degrees abduction
- Internal rotation with the elbow up to 90 degrees abduction
Who cannot join
- Has received treatment for adhesive capsulitis or is planning to receive treatment for adhesive capsulitis at any time during the study including but not limited to:
- physical therapy or acupuncture within 2 weeks before the first injection of study drug
- intra-articular or intrabursal injection(s) of lidocaine; suprascapular nerve blocks; corticosteroids, electroanalgesic and/or thermoanalgesic modalities within 1 month before the screening visit
- intra-articular or intrabursal injection(s) of sodium hyaluronate and/or glenohumeral distension arthrography within 3 months before the screening visit
- surgical intervention (including shoulder manipulation under anesthesia) at any time
- Has any of the following conditions, as determined by investigator to be potentially confounding to the evaluation of safety and efficacy:
Show all 31Show fewer
- Adhesive capsulitis as a result of traumatic injury (ie, direct injury to the shoulder such as fracture of the humerus or clavicle immediately preceding the onset of this episode of adhesive capsulitis). Traumatic events in the past that are not temporally related to the onset of this episode of adhesive capsulitis would not necessarily exclude a subject from participating in the study.
- Active subacromial impingement in the affected shoulder
- Calcified tendonitis in the affected shoulder
- Glenohumeral joint arthritis in the affected shoulder
- Arthrosis of the affected shoulder
- Chondrolysis of the affected shoulder
- Subscapularis tendon rupture of the affected shoulder
- Other rotator cuff injuries of the affected shoulder
- Uncontrolled hypertension
- Uncontrolled diabetes
- Uncontrolled thyroid disease
- History of thrombosis or post-thrombosis syndrome
- Physical impairment that would preclude performing the protocol defined exercises
- Active infection in area to be treated
- Clinically significant neurological disease
- Bleeding disorder
- Chronic use of anticoagulation medications and the subject cannot be cleared medically to stop taking medication for 7 days prior to each injection. Less than or equal to 150 mg aspirin is allowed during the study.
- Known active hepatitis A, B, or C
- Other significant medical condition (eg, morbid obesity, cervical disc disease), which in the investigator's opinion would make the subject unsuitable for enrollment in the study
- Has received oral or intravenous steroids for any reason within 3 weeks before the screening visit
- Has received an investigational drug or treatment within 30 days before the first dose of study drug.
- Has a known allergy to collagenase or any other excipient of AA4500 or any other procedural medication.
- Has, at any time, received collagenase for the treatment of adhesive capsulitis.
- Is unable to undergo an x-ray or MRI (contraindication) evaluation of the affected shoulder.
- Is planning to be treated with commercial XIAFLEX at any time during the study.
Trial locations and contacts
46 sites in 2 countries.
46 sites in 2 countries
United States35 sites
Blair Orthopedic Associates, Inc.
Altoona, Pennsylvania, 16602
Commonwealth Orthopaedics & Rehabilitation
Arlington, Virginia, 22205
Texas Orthopedic Specialist
Bedford, Texas, 76021
The Neuromusculoskeletal Center of the Cascades d.b.a. The Center
Bend, Oregon, 97701
Alabama Orthopaedic Center-Research
Birmingham, Alabama, 35209
Injury Care Medical Center
Boise, Idaho, 83713
Advance Med Clinical Research
Carlsbad, California, 92008
Danville Orthopedic Clinic, Inc.
Danville, Virginia, 24541
Florida Research Associates
DeLand, Florida, 32720
Triangle Orthopedic Associates, PA
Durham, North Carolina, 27704
Triwest Research Associates
El Cajon, California, 92020
Core Orthopedic Medical Center
Encinitas, California, 92024
Colorado Orthopedic Consultants, PC
Englewood, Colorado, 80110
Shrock Orthopedic Research, LLC
Fort Lauderdale, Florida, 33316
Great Falls Clinic
Great Falls, Montana, 59405
Bone and Joint Clinic
Gretna, Louisiana, 70056
Centex Studies
Houston, Texas, 77062
Indiana Hand to Shoulder Center
Indianapolis, Indiana, 46260
Nevada Orthopedic & Spine Center
Las Vegas, Nevada, 89128
Central Kentucky Research Associates
Lexington, Kentucky, 40509
Non-Surgical Orthopedics, P.C. / Georgia Institute for Clinical Research, LLC
Marietta, Georgia, 30060
MedPharmics, LLC
Metairie, Louisiana, 70006
Coastal Clinical Research
Mobile, Alabama, 36608
Temecula Rheumatology & Internal Medicine
Murrieta, California, 92563
Jewett Orthopedic Clinic
Orlando, Florida, 32822
University of Pennsylvania Penn Orthopaedics
Philadelphia, Pennsylvania, 19087
Arizona Research Center, Inc.
Phoenix, Arizona, 85023
Wake Research Associates
Raleigh, North Carolina, 27612
Rockford Orthopedic Associates
Rockford, Illinois, 61107
Rockford Orthopedics Associates
Rockford, Illinois, 61114
Clearview Medical Research
Santa Clarita, California, 91350
Stony Brook University Medical Center (SUNY)
Stony Brook, New York, 11794
Clinical Research of West Florida
Tampa, Florida, 33603
Arthritis and Rheumatism Associates, PC
Wheaton, Maryland, 20902
PRN of Kansas
Wichita, Kansas, 67203
Australia11 sites
Hunter Clinical Research
NSW
Royal Prince Alfred
NSW
St George Hospital
NSW
Peninsula Private Hospital
Queensland
QPharm
Queensland
Sports Medicine Professionals
Richmond, Victoria, 3121
Menzies Research Institute
Tasmania
Emeritus Research
VIC
Epworth Hospital
VIC
Repatriation Hospital
VIC
Hand and Upper Limb Centre
WA
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of AA4500 for the Treatment of Adhesive Capsulitis of the Shoulder
The objectives of this study are to assess the safety, effectiveness, and immunogenicity of AA4500 in the treatment of adhesive capsulitis.
Read the detailed description
Study is a Phase 2b, double-blind, placebo-controlled study of the safety and efficacy of AA4500 for the treatment of adhesive capsulitis of the shoulder. To be eligible for treatment, a subject must have unilateral idiopathic adhesive capsulitis of the shoulder with restricted range of motion in the affected shoulder for at least 3 months but not more than 12 months. Subjects will be screened for study eligibility within 28 days before injection of study drug.
Approximately 300 adult women and men are to be enrolled in this study. Following screening and determination of study eligibility, subjects will be randomized 3:1 to receive 0.58 mg of AA4500 or placebo. Subjects will receive up to 3 injections of study drug. Each injection will be separated by a minimum of 21 days. Subjects will also be instructed in home shoulder exercises after the first injection.
- Conditions
- Adhesive Capsulitis, Frozen Shoulder
- Being tested
- Collagenase Clostridium Histolyticum, Placebo
- Keywords
- Adhesive Capsulitis, Frozen Shoulder, Shoulder Range of Motion limitation, Shoulder Pain
- Medical subject headings
- Bursitis, Shoulder Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Collagenase Clostridium HistolyticumBiological
Also called AA4500, Xiaflex, Xiapex
Treatment of Adhesive Capsulitis
PlaceboOther
Placebo injection
| Study group | Role | What they receive |
|---|---|---|
| Collagenase Clostridium Histolyticum | Experimental | Up to 3 injections of .58 mg/1 mL of collagenase clostridium histolyticum (CCH), minimum of 21 days apart and home shoulder exercise. Receives: Biological: Collagenase Clostridium Histolyticum |
| Placebo | Placebo comparator | Up to 3 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Day 95 in Active Forward Flexion
Active range of motion (AROM) measurement using a goniometer to assess forward flexion in the affected shoulder
Measured: Baseline, day 95
Secondary outcomes (12)
Change From Baseline to Day 95 in Adapted American Shoulder and Elbow Surgeons (ASES) Function Subscale
Function subscale score ranging from 0-50, with 0 being most dysfunctional, derived from participant assessment of ability to do 10 activities with affected shoulder/arm where 0=unable to do to, 1=very difficult to do, 2=somewhat difficult, and 3=not difficult, and calculated as (cumulative total score for the 10 activity items) × (5/3); adapted from ASES Standardized Shoulder Assessment Form, Patient Self-Evaluation (United States adapted version).
Measured: Baseline, day 95
Change From Baseline to Day 95 in Pain With Movement Using 11-point Numeric Rating Scale (NRS)
Participant assessment of pain in response to "How bad is the pain upon movement of your affected shoulder at its worst in the last 24 hours?" using an 11-point NRS where 0=no pain at all and 10=pain as bad as it can be.
Measured: Baseline, day 95
Change From Baseline to Day 95 in Active Abduction
AROM measurement using a goniometer to assess abduction in the affected shoulder
Measured: Baseline, day 95
Change From Baseline to Day 95 in Passive Forward Flexion
Passive range of motion (PROM) measurement using a goniometer to assess forward flexion in the affected shoulder
Measured: Baseline, day 95
Change From Baseline to Day 95 in Passive Abduction
PROM measurement using a goniometer to assess abduction in the affected shoulder
Measured: Baseline, day 95
Change From Baseline to Day 95 in Active Internal Rotation
AROM measurement using a goniometer to assess internal rotation in the affected shoulder
Measured: Baseline, day 95
Change From Baseline to Day 95 in Active External Rotation
AROM measurement using a goniometer to assess external rotation in the affected shoulder
Measured: Baseline, day 95
Change From Baseline to Day 95 in Passive Internal Rotation
PROM measurement using a goniometer to assess internal rotation in the affected shoulder
Measured: Baseline, day 95
Change From Baseline to Day 95 in Passive External Rotation
PROM measurement using a goniometer to assess external rotation in the affected shoulder
Measured: Baseline, day 95
Change From Baseline to Day 95 in Adapted ASES Pain Subscale
Pain subscale score ranging from 0-50, with 0 being greatest pain, derived from participant overall assessment of pain in response to "How bad is the pain in your affected shoulder today?" using an 11-point NRS where 0=no pain at all and 10=pain as bad as it can be and calculated as (10 - NRS score) x 5; adapted from ASES Standardized Shoulder Assessment Form, Patient Self-Evaluation
Measured: Baseline, day 95
Subject Satisfaction With Treatment at Day 95
Participant assessment of satisfaction with treatment rated as very satisfied, quite satisfied, neither satisfied nor dissatisfied, quite dissatisfied, or very dissatisfied.
Measured: Day 95
Investigator Assessment of Improvement With Treatment at Day 95
Investigator assessment of degree of improvement in severity of the participant's treated shoulder compared with screening rated as very much improved, much improved, minimally improved, no change, minimally worse, much worse, or very much worse.
Measured: Day 95
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2013 (estimated)
- Study startNov 2013
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adhesive CapsulitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 322 participants (actual)
Sponsor and investigators
- Lead sponsor
- Endo USA Inc., a Keenova Therapeutics Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Neil H Schusterman, MD FACP, Study director, Endo USA Inc., a Keenova Therapeutics Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02006719
- Sponsor's protocol ID
- AUX-CC-871
- Acronym
- AC
- Status last verified
- Sep 2017
- First submitted
- 2 Dec 2013
- Last updated
- 5 Oct 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of AA4500 for the Treatment of Adhesive Capsulitis of the Shoulder
- ClinicalTrials.gov ID
- NCT02006719
- Acronym / sponsor ID
- AC / AUX-CC-871
- Conditions
- Adhesive Capsulitis, Frozen Shoulder
- Keywords
- Adhesive Capsulitis, Frozen Shoulder, Shoulder Range of Motion limitation, Shoulder Pain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 322 participants (actual)
- Lead sponsor
- Endo USA Inc., a Keenova Therapeutics CompanyIndustry (pharma, biotech, devices)
- Study start
- Nov 2013
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 10 Dec 2013 (estimated)
- Results
- Posted 25 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objectives of this study are to assess the safety, effectiveness, and immunogenicity of AA4500 in the treatment of adhesive capsulitis.
Detailed description
Study is a Phase 2b, double-blind, placebo-controlled study of the safety and efficacy of AA4500 for the treatment of adhesive capsulitis of the shoulder. To be eligible for treatment, a subject must have unilateral idiopathic adhesive capsulitis of the shoulder with restricted range of motion in the affected shoulder for at least 3 months but not more than 12 months. Subjects will be screened for study eligibility within 28 days before injection of study drug.
Approximately 300 adult women and men are to be enrolled in this study. Following screening and determination of study eligibility, subjects will be randomized 3:1 to receive 0.58 mg of AA4500 or placebo. Subjects will receive up to 3 injections of study drug. Each injection will be separated by a minimum of 21 days. Subjects will also be instructed in home shoulder exercises after the first injection.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Collagenase Clostridium Histolyticum | Experimental | Biological: Collagenase Clostridium HistolyticumUp to 3 injections of .58 mg/1 mL of collagenase clostridium histolyticum (CCH), minimum of 21 days apart and home shoulder exercise. |
| Placebo | Placebo comparator | Other: PlaceboUp to 3 1-mL injections of placebo, minimum of 21 days apart and home shoulder exercise. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Unilateral idiopathic adhesive capsulitis of one shoulder for at least 3 months but not more than 12 months (Frozen Stage)
- Normal range of motion in the contralateral shoulder
- Restricted active range of motion (AROM) in the affected shoulder defined as: a deficit of at least 60 degrees in total AROM in the affected shoulder as compared with the total AROM in the contralateral shoulder and a deficit of at least 30 degrees in AROM in at least one of the following planes as compared with the contralateral shoulder:
Key exclusion criteria (31 listed)
- Has received treatment for adhesive capsulitis or is planning to receive treatment for adhesive capsulitis at any time during the study including but not limited to:
- Has any of the following conditions, as determined by investigator to be potentially confounding to the evaluation of safety and efficacy:
- Has received oral or intravenous steroids for any reason within 3 weeks before the screening visit
- Has received an investigational drug or treatment within 30 days before the first dose of study drug.
- Has a known allergy to collagenase or any other excipient of AA4500 or any other procedural medication.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Collagenase Clostridium HistolyticumAlso: AA4500, Xiaflex, XiapexTreatment of Adhesive Capsulitis | Biological | Collagenase Clostridium Histolyticum |
| PlaceboPlacebo injection | Other | Placebo |
Primary outcome
Change From Baseline to Day 95 in Active Forward Flexion
Time frame: Baseline, day 95
Active range of motion (AROM) measurement using a goniometer to assess forward flexion in the affected shoulder
12 secondary outcomes
Change From Baseline to Day 95 in Adapted American Shoulder and Elbow Surgeons (ASES) Function Subscale
Time frame: Baseline, day 95
Change From Baseline to Day 95 in Pain With Movement Using 11-point Numeric Rating Scale (NRS)
Time frame: Baseline, day 95
Change From Baseline to Day 95 in Active Abduction
Time frame: Baseline, day 95
Change From Baseline to Day 95 in Passive Forward Flexion
Time frame: Baseline, day 95
Change From Baseline to Day 95 in Passive Abduction
Time frame: Baseline, day 95
Change From Baseline to Day 95 in Active Internal Rotation
Time frame: Baseline, day 95
Change From Baseline to Day 95 in Active External Rotation
Time frame: Baseline, day 95
Change From Baseline to Day 95 in Passive Internal Rotation
Time frame: Baseline, day 95
Change From Baseline to Day 95 in Passive External Rotation
Time frame: Baseline, day 95
Change From Baseline to Day 95 in Adapted ASES Pain Subscale
Time frame: Baseline, day 95
Subject Satisfaction With Treatment at Day 95
Time frame: Day 95
Investigator Assessment of Improvement With Treatment at Day 95
Time frame: Day 95
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Adhesive Capsulitis of the Shoulder, Frozen Shoulder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Neil H Schusterman, MD FACP study director
Endo USA Inc., a Keenova Therapeutics Company
46 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Collagenase Clostridium Histolyticum in people with Adhesive Capsulitis and Frozen Shoulder, run by Endo USA Inc., a Keenova Therapeutics Company at 46 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 46 sites in United States, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline to Day 95 in Active Forward Flexion (time frame: Baseline, day 95). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2017.