Hemophilic ArthropathyPhase 2NCT02994147
A Proof-of-Concept Study of AC-201 Controlled-Release Tablet (CR Tablet) in Patients With Hemophilic Arthropathy
A Phase 2 study testing AC-201CR in people with Hemophilic Arthropathy, run by TWi Biotechnology, Inc. at 1 site in Taiwan.
Trial summary
Repeated joint bleeding leads to hemophilic arthropathy (HA), which manifests with chronic synovitis, cartilage damage and bony destruction. Currently available treatments of HA, including analgesics, NSAIDs, and hyaluronic acid, are predominantly directed toward the symptomatic relief of pain and inflammation, with… Read more about this study
- Who is it for?
- Ages 20 to 65 years, men only
- Conditions the study is for
- Hemophilic Arthropathy
- What is being tested?
- AC-201CR
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 1 siteTaiwan
- Study dates
- 21 Mar 2017to 2 Oct 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 20 to 65 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male age 20 to 65 years, inclusive
- Diagnosis of Hemophilia A or B
- Clinical diagnosis of hemophilic arthropathy in the knee(s) for at least 6 months
- Pettersson score (based on X-ray) of 0 to 4 in at least one knee within 1 year of screening
- IPSG (2012) overall score of 3 to 9 (based on MRI) in at least one knee at screening
- Is able to read, understand, and sign the Informed Consent Form (ICF), communicate with the investigator, complete study diaries, and understand and comply with protocol requirements
Who cannot join
- Total knee replacement in the primary knee
- Presence of joint infections in the primary knee
- Knee surgery within 6 months prior to screening in the primary knee
- Intra-articular hyaluronic acid (IAHA) or platelet-rich plasma (PRP) injection in the primary knee within 6 months prior to screening
- Use of any of the following medications after the screening visit:
- NSAID injection (oral NSAIDs including COX-2 inhibitors allowed)
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- Glucosamine or chondroitin
- History of high responder inhibitory antibodies to factor VIII or factor IX clotting factor, with titer >5 Bethesda units (BU), OR clinical evidence for presence of factor inhibitor
- History of rheumatoid arthritis or gouty arthropathy
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) concentration >2x the upper limit of laboratory normal range (ULN), or bilirubin >1.5x ULN at screening
- Positive test for human immunodeficiency virus (HIV), hepatitis B virus (HBV), or TB
Trial locations and contacts
1 site in 1 country.
About this study
Repeated joint bleeding leads to hemophilic arthropathy (HA), which manifests with chronic synovitis, cartilage damage and bony destruction. Currently available treatments of HA, including analgesics, NSAIDs, and hyaluronic acid, are predominantly directed toward the symptomatic relief of pain and inflammation, with no or little effect on joint cartilage degeneration. AC201CR, a control released formulation of AC-201, demonstrates anti-inflammatory effects by reducing NLRP3 inflammasome assembly. AC-201 is also unique in that it influences both the anabolism and catabolism of chondrocytes in vitro and has shown cartilage-sparing properties in animal studies. The study is designed to evaluate the joint structure-modifying and symptom-relieving effects, safety, and tolerability of AC-201CR in subjects with HA.
- Conditions
- Hemophilic Arthropathy
- Being tested
- Placebo, AC-201CR
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo-only control study medication is the same formulation as active treatment without active ingredient
AC-201CRDrug
The investigational product is formulated as controlled-release (CR) tablets
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 1. Subjects will initiate blinded study medication at a once daily (QD) regimen for 4 weeks, then titrate to twice daily (BID) for the remainder of the 24-week blinded treatment period.
2. At Week 24, subjects will discontinue blinded study medication and start open-label treatment with AC-201CR. All subjects will initiate open-label AC-201CR QD for 4 weeks, then titrate to BID for the remainder of the study. Receives: Drug: Placebo |
| AC-201CR 72mg | Experimental | 1. Subjects will initiate blinded study medication at a once daily (QD) regimen for 4 weeks, then titrate to twice daily (BID) for the remainder of the 24-week blinded treatment period.
2. At Week 24, subjects will discontinue blinded study medication and start open-label treatment with AC-201CR. All subjects will initiate open-label AC-201CR QD for 4 weeks, then titrate to BID for the remainder of the study. Receives: Drug: AC-201CR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in IPSG (MRI) score for primary knee
Knee arthropathy will be evaluated according to the 2012 IPSG (International Prophylaxis Study Group) rating scale. This scale is an additive scale with maximum value up to 17 points, comprising 2 subscores of soft tissue changes (maximum 9 points) and osteochondral changes (maximum 8 points).
Measured: 24 Weeks
Secondary outcomes (8)
Change from baseline in IPSG (MRI) score for non-primary knee
Measured: 24 Weeks
Change from baseline in IPSG score by knee
Measured: 48 Weeks
Change from baseline in IPSG component scores by knee
Measured: 24 Weeks and 48 Weeks
Change from baseline in MRI-measured synovial thickness by knee
Measured: 24 Weeks and 48 Weeks
Change from baseline in ultrasonographic synovial thickness by knee
Measured: 24 Weeks and 48 Weeks
Change from baseline in ultrasonographic hyperemia score by knee
Measured: 24 Weeks and 48 Weeks
Change from baseline in knee pain (by VAS) by knee
Measured: 4, 12, 24, 28, 36 and 48 Weeks
Change from baseline in Short Form-36 score
Measured: 24 Weeks and 48 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2016 (estimated)
- Study start21 Mar 2017
- Primary completion18 Apr 2019
- Study completion2 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophilic ArthropathyStudies 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
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- TWi Biotechnology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02994147
- Sponsor's protocol ID
- AC-201CR-HA-001
- Status last verified
- Jul 2020
- First submitted
- 9 Dec 2016
- Last updated
- 9 Jul 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof-of-Concept Study of AC-201 Controlled-Release Tablet (CR Tablet) in Patients With Hemophilic Arthropathy
- ClinicalTrials.gov ID
- NCT02994147
- Acronym / sponsor ID
- AC-201CR-HA-001
- Conditions
- Hemophilic Arthropathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- TWi Biotechnology, Inc.Industry (pharma, biotech, devices)
- Study start
- 21 Mar 2017 (actual)
- Primary completion
- 18 Apr 2019 (actual)
- Study completion
- 2 Oct 2019 (actual)
- First posted
- 15 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Repeated joint bleeding leads to hemophilic arthropathy (HA), which manifests with chronic synovitis, cartilage damage and bony destruction. Currently available treatments of HA, including analgesics, NSAIDs, and hyaluronic acid, are predominantly directed toward the symptomatic relief of pain and inflammation, with no or little effect on joint cartilage degeneration. AC201CR, a control released formulation of AC-201, demonstrates anti-inflammatory effects by reducing NLRP3 inflammasome assembly. AC-201 is also unique in that it influences both the anabolism and catabolism of chondrocytes in vitro and has shown cartilage-sparing properties in animal studies. The study is designed to evaluate the joint structure-modifying and symptom-relieving effects, safety, and tolerability of AC-201CR in subjects with HA.
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 |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo1. Subjects will initiate blinded study medication at a once daily (QD) regimen for 4 weeks, then titrate to twice daily (BID) for the remainder of the 24-week blinded treatment period. 2. At Week 24, subjects will discontinue blinded study medication and start open-label treatment with AC-201CR. All subjects will initiate open-label AC-201CR QD for 4 weeks, then titrate to BID for the remainder of the study. |
| AC-201CR 72mg | Experimental | Drug: AC-201CR1. Subjects will initiate blinded study medication at a once daily (QD) regimen for 4 weeks, then titrate to twice daily (BID) for the remainder of the 24-week blinded treatment period. 2. At Week 24, subjects will discontinue blinded study medication and start open-label treatment with AC-201CR. All subjects will initiate open-label AC-201CR QD for 4 weeks, then titrate to BID for the remainder of the study. |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male age 20 to 65 years, inclusive
- Diagnosis of Hemophilia A or B
- Clinical diagnosis of hemophilic arthropathy in the knee(s) for at least 6 months
- Pettersson score (based on X-ray) of 0 to 4 in at least one knee within 1 year of screening
- IPSG (2012) overall score of 3 to 9 (based on MRI) in at least one knee at screening
Key exclusion criteria (11 listed)
- Total knee replacement in the primary knee
- Presence of joint infections in the primary knee
- Knee surgery within 6 months prior to screening in the primary knee
- Intra-articular hyaluronic acid (IAHA) or platelet-rich plasma (PRP) injection in the primary knee within 6 months prior to screening
- Use of any of the following medications after the screening visit:
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 |
|---|---|---|
| PlaceboPlacebo-only control study medication is the same formulation as active treatment without active ingredient | Drug | Placebo |
| AC-201CRThe investigational product is formulated as controlled-release (CR) tablets | Drug | AC-201CR 72mg |
Primary outcome
Change from baseline in IPSG (MRI) score for primary knee
Time frame: 24 Weeks
Knee arthropathy will be evaluated according to the 2012 IPSG (International Prophylaxis Study Group) rating scale. This scale is an additive scale with maximum value up to 17 points, comprising 2 subscores of soft tissue changes (maximum 9 points) and osteochondral changes (maximum 8 points).
8 secondary outcomes
Change from baseline in IPSG (MRI) score for non-primary knee
Time frame: 24 Weeks
Change from baseline in IPSG score by knee
Time frame: 48 Weeks
Change from baseline in IPSG component scores by knee
Time frame: 24 Weeks and 48 Weeks
Change from baseline in MRI-measured synovial thickness by knee
Time frame: 24 Weeks and 48 Weeks
Change from baseline in ultrasonographic synovial thickness by knee
Time frame: 24 Weeks and 48 Weeks
Change from baseline in ultrasonographic hyperemia score by knee
Time frame: 24 Weeks and 48 Weeks
Change from baseline in knee pain (by VAS) by knee
Time frame: 4, 12, 24, 28, 36 and 48 Weeks
Change from baseline in Short Form-36 score
Time frame: 24 Weeks and 48 Weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2020.
- Individual participant dataSharing planned: No
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Multicomponent Pain Self-Management in Adults With Haemophilic Arthropathy
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Real-World Joint Outcomes After Selective Transition to Low-Dose Emicizumab in Pediatric Hemophilia A
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AC-201CR in people with Hemophilic Arthropathy, run by TWi Biotechnology, Inc. at 1 site in Taiwan.
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 6 inclusion and 11 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 9 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 in IPSG (MRI) score for primary knee (time frame: 24 Weeks). 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 9 Jul 2020.