Safety and Tolerability Study of AVID200 in Pts With Diffuse Cutaneous Systemic Sclerosis

NCT03831438 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AVID200-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 4

Brief 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. 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.

Conditions

Scleroderma, Diffuse

Outcome Measures

Primary Outcomes (1)

• Primary Outcome: Incidence of treatment related adverse events

  Incidence of treatment related adverse events

  10 Months

Study Arms (1)

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).

Drug: AVID200

Interventions

AVID200 DRUG

Intravenous infusion of AVID200 Q2 weeks for 3 doses

Also known as: AVID200 DP

Dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (4)

UCLA

Los Angeles, California, 90095, United States

Location

Hospital of Special Surgery

New York, New York, 10035, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Scleroderma, Diffuse

Condition Hierarchy (Ancestors)

Scleroderma, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Robert Lafyatis, MD

  University of Pittsburgh Medical Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, uncontrolled, non-randomized study, escalating doses of study drug in sequential patient cohorts

Study Record Dates

• First Submitted: January 31, 2019
• First Posted: February 5, 2019
• Study Start: January 1, 2019
• Primary Completion: June 20, 2020
• Study Completion: June 20, 2020
• Last Updated: November 19, 2024

Record last verified: 2024-11

Locations

US (4)