Scleroderma, DiffusePhase 1NCT03831438
Safety and Tolerability Study of AVID200 in Pts With Diffuse Cutaneous Systemic Sclerosis
A Phase 1 study testing AVID200 in people with Scleroderma, Diffuse, run by Bristol-Myers Squibb at 4 sites in United States.
Trial summary
Several lines of evidence place TGF-β, a potent pro-fibrotic cytokine, at the centre of the pathogenesis of Systemic Sclerosis (SSC). AVID200 is a novel inhibitor of TGF-β ligands. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Scleroderma, Diffuse
- What is being tested?
- AVID200
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 4 sitesUnited States
- Study dates
- 1 Jan 2019to 20 Jun 2020
- Phase
- Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with the ability to understand and give written informed consent
- Male or female patients, ≥ 18 years
- Patients classified as having systemic sclerosis (SSc) with a total ≥ 9 according to the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for the classification of SSc
- Patients classified as having diffuse cutaneous SSc (dcSSc) subset
- Patients with < 5 years since the onset of first SSc manifestations, other than Raynaud's phenomenon, at the time of enrollment
- Patients with a MRSS ≥ 15, and with a score that has not decreased by > 5 points in the past 2 months (8 weeks)
- Patients with a skin score ≥ 2 on at least one forearm
- Persons of childbearing potential agreeing to use a highly effective, non-hormonal method of contraception during the study
Who cannot join
- Women who are pregnant or intending to become pregnant before study, during study or within 3 months after the last dose of study drug; women who are breastfeeding
- Patients with any of the following hematologic abnormalities at baseline:
- Hemoglobin < 10.0 g/dL*
- Absolute neutrophil count (ANC) < 1,500 per mm3
- Platelet count < 100,000 per mm3
- Iron, iron binding, and transferrin studies to be performed at screening; patients with documented iron deficiency to receive repletion prior to receiving study drug
Show all 37Show fewer
- Patients with any of the following serum chemistry abnormalities at baseline:
- Total bilirubin ≥ 1.5 × the ULN for the institution
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 2.5 × the ULN for the institution (≥ 5× ULN if due to hepatic involvement by disease)
- History of scleroderma renal crisis within 6 months or creatinine > 2.0 mg/dL
- Lack of intravenous (IV) access required for study drug administration
- History of organ transplantation (e.g., stem cell or solid organ)
- Patients with:Active uncontrolled bleeding or a known bleeding diathesis, Active thrombosis, thrombophlebitis, thromboembolism, or hypercoagulable state
- Patients with a significant cardiovascular disease or condition, including:
- Congestive heart failure (CHF), Left ventricular ejection fraction (LVEF) known to be below the lower limit of normal (LLN) for the center, or < 50% by multi-gated acquisition (MUGA) scan or echocardiogram (ECHO) if no LLN is defined by the site
- Need for antiarrhythmic medical therapy for a significant ventricular arrhythmia or other uncontrolled arrhythmia
- Severe conduction disturbance (i.e., trifascicular heart block)
- QTc interval ≥ 480 msec
- Uncontrolled hypertension (per the Investigator's discretion)
- History of acute coronary disease (including myocardial infarction [MI] and angina), coronary angioplasty, stenting, or bypass surgery within 2 years
- Patients with a significant pulmonary disease or condition
- History of ascites or pleural effusion, unless successfully treated and completely resolved and the patient has not been treated for the conditions for > 4 months prior to first study drug administration
- Significant gastrointestinal (GI) or hepatic disease or condition, including but not limited to:
- GI involvement requiring total parenteral nutrition or hospitalization for pseudo-obstruction within 3 months prior to first study drug administration
- Moderate to severe hepatic impairment (i.e., Child-Pugh Class B or C)
- Patients with an active malignancy or history of a malignancy within the last 2 years with specified exceptions
- Patients with a known or suspected hypersensitivity to any of the excipients of formulated AVID200
- Patients with any of the following, Human immunodeficiency virus (HIV) infection (i.e., HIV RNA-positive)
- Active/chronic infection with hepatitis B virus (HBV) (i.e., HB surface antigen [HBsAg]-positive, HB surface antibody [HBsAb]-negative)
- Active/chronic infection with hepatitis C virus (HCV) (i.e., HCV RNA-positive)
- Patients with known active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of the nail bed), or any other serious/active/uncontrolled infection, any infection requiring hospitalization or treatment with parenteral antibiotics, or unexplained fever > 38.5ºC within 4 weeks prior to first study drug administration
- Patients with unresolved > Grade 1 adverse event (AE) associated with any prior therapy for dcSSc
- Patients with inadequate recovery from any prior surgical procedure, or patients having undergone any major surgical procedure within 4 weeks prior to first study drug administration
- Patients with any other serious, life-threatening, or unstable preexisting medical condition (aside from the underlying diagnosis), including significant organ system dysfunction, or clinically significant laboratory abnormality (ies), which, in the opinion of the Investigator, would either compromise the patient's safety, significantly increase the risk of SAEs, limit life expectancy, or interfere with obtaining informed consent, compliance with study procedures, or evaluation of the safety of the study drug
- Patients with ongoing drug or alcohol abuse that would impact compliance with study-related procedures or evaluations
- Patients with a psychiatric disorder, or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary study-related evaluations
- Patients with the inability or with foreseeable incapacity, in the opinion of the Investigator, to comply with the protocol requirements
Trial locations and contacts
4 sites in 1 country.
United States4 sites
UCLA
Los Angeles, California, 90095
Hospital of Special Surgery
New York, New York, 10035
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
Official title: A Phase 1 Open-Label Study to Determine the Safety and Tolerability of AVID200: A Transforming Growth Factor β (TGFβ) Inhibitor, in Patients With Diffuse Cutaneous Systemic Sclerosis
Several lines of evidence place TGF-β, a potent pro-fibrotic cytokine, at the centre of the pathogenesis of Systemic Sclerosis (SSC). AVID200 is a novel inhibitor of TGF-β ligands. This Phase 1 trial is designed to evaluate the safety, tolerability and preliminary efficacy of AVID200 in SSc patients in order delineate doses to be further evaluated in Phase 2. Approximately 9 to 24 male and female patients with documented SSc (i.e., score ≥ 9 according to the American College of Rheumatology/European League Against Rheumatism classification criteria), and classified as having the diffuse cutaneous SSs (dcSSc) subset (i.e., according to the LeRoy and Medsger Classification), will be entered into this Phase 1a, multicentre, open-label, dose-escalation, cohort study of AVID200.
Read the detailed description
The trial is designed to evaluate the safety and tolerability of sequential escalating doses of AVID200 (study drug), in order delineate a potential effective range of tolerated doses to be further evaluated in Phase 2.
Patients will be treated and followed on an outpatient basis throughout the trial, unless hospitalization is required for other reasons, or to assure patient safety. The choice of doses for further Phase 2 study will be based on clinical and laboratory data obtained during this trial, including safety, PK, and preliminary anti-fibrotic activity.
Upon completion of Cycle 1, and provided re-treatment criteria are met, patients may receive up to 2 additional cycles of study drug unless a criterion for treatment discontinuation has been met.
- Conditions
- Scleroderma, Diffuse
- Being tested
- AVID200
- Medical subject headings
- Scleroderma, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AVID200Drug
Also called AVID200 DP
Intravenous infusion of AVID200 Q2 weeks for 3 doses
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation | Other | Sequential escalating doses of AVID200 when administered once every 2 weeks (Q2W) by 1-hour intravenous (IV) infusion to patient cohorts with diffuse cutaneous systemic sclerosis (dcSSc).
Each 2-week dosing period equals 1 cycle; patients may receive up to 3 cycles of AVID200 (i.e., dosing on D1, 15, and 29 of overall 6 week treatment period). Receives: Drug: AVID200 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Outcome: Incidence of treatment related adverse events
Incidence of treatment related adverse events
Measured: 10 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2019
- Study start1 Jan 2019
- Primary completion20 Jun 2020
- Study completion20 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Scleroderma, DiffuseStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open-label, uncontrolled, non-randomized study, escalating doses of study drug in sequential patient cohorts
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert Lafyatis, MD, Study chair, University of Pittsburgh Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03831438
- Sponsor's protocol ID
- AVID200-01
- Status last verified
- Nov 2024
- First submitted
- 31 Jan 2019
- Last updated
- 19 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Open-Label Study to Determine the Safety and Tolerability of AVID200: A Transforming Growth Factor β (TGFβ) Inhibitor, in Patients With Diffuse Cutaneous Systemic Sclerosis
- ClinicalTrials.gov ID
- NCT03831438
- Acronym / sponsor ID
- AVID200-01
- Conditions
- Scleroderma, Diffuse
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 20 Jun 2020 (actual)
- Study completion
- 20 Jun 2020 (actual)
- First posted
- 5 Feb 2019 (actual)
- 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.
Several lines of evidence place TGF-β, a potent pro-fibrotic cytokine, at the centre of the pathogenesis of Systemic Sclerosis (SSC). AVID200 is a novel inhibitor of TGF-β ligands. This Phase 1 trial is designed to evaluate the safety, tolerability and preliminary efficacy of AVID200 in SSc patients in order delineate doses to be further evaluated in Phase 2. Approximately 9 to 24 male and female patients with documented SSc (i.e., score ≥ 9 according to the American College of Rheumatology/European League Against Rheumatism classification criteria), and classified as having the diffuse cutaneous SSs (dcSSc) subset (i.e., according to the LeRoy and Medsger Classification), will be entered into this Phase 1a, multicentre, open-label, dose-escalation, cohort study of AVID200.
Detailed description
The trial is designed to evaluate the safety and tolerability of sequential escalating doses of AVID200 (study drug), in order delineate a potential effective range of tolerated doses to be further evaluated in Phase 2.
Patients will be treated and followed on an outpatient basis throughout the trial, unless hospitalization is required for other reasons, or to assure patient safety. The choice of doses for further Phase 2 study will be based on clinical and laboratory data obtained during this trial, including safety, PK, and preliminary anti-fibrotic activity.
Upon completion of Cycle 1, and provided re-treatment criteria are met, patients may receive up to 2 additional cycles of study drug unless a criterion for treatment discontinuation has been met.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open-label, uncontrolled, non-randomized study, escalating doses of study drug in sequential patient cohorts
| Arm | Type | Receives |
|---|---|---|
| Dose escalation | Other | Drug: AVID200Sequential escalating doses of AVID200 when administered once every 2 weeks (Q2W) by 1-hour intravenous (IV) infusion to patient cohorts with diffuse cutaneous systemic sclerosis (dcSSc). Each 2-week dosing period equals 1 cycle; patients may receive up to 3 cycles of AVID200 (i.e., dosing on D1, 15, and 29 of overall 6 week treatment period). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients with the ability to understand and give written informed consent
- Male or female patients, ≥ 18 years
- Patients classified as having systemic sclerosis (SSc) with a total ≥ 9 according to the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for the classification of SSc
- Patients classified as having diffuse cutaneous SSc (dcSSc) subset
- Patients with < 5 years since the onset of first SSc manifestations, other than Raynaud's phenomenon, at the time of enrollment
Key exclusion criteria (37 listed)
- Women who are pregnant or intending to become pregnant before study, during study or within 3 months after the last dose of study drug; women who are breastfeeding
- Patients with any of the following hematologic abnormalities at baseline:
- Patients with any of the following serum chemistry abnormalities at baseline:
- History of scleroderma renal crisis within 6 months or creatinine > 2.0 mg/dL
- Lack of intravenous (IV) access required for study drug administration
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 |
|---|---|---|
| AVID200Also: AVID200 DPIntravenous infusion of AVID200 Q2 weeks for 3 doses | Drug | Dose escalation |
Primary outcome
Primary Outcome: Incidence of treatment related adverse events
Time frame: 10 Months
Incidence of treatment related adverse events
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 19 Nov 2024.
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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.
Robert Lafyatis, MD study chair
University of Pittsburgh Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AVID200 in people with Scleroderma, Diffuse, run by Bristol-Myers Squibb at 4 sites in United States.
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 8 inclusion and 37 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 19 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Primary Outcome: Incidence of treatment related adverse events (time frame: 10 Months). 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 19 Nov 2024.