NCT03895112

MPN-RC 118 AVID200 in Myelofibrosis

Phase I Study of AVID200 in Patients With Myelofibrosis (Myeloproliferative Neoplasms Research Consortium [MPN-RC] 118)

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 21 (actual)
• Sponsor: John Mascarenhas · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Increased levels of TGF-β1 were detected in serum, plasma and BM and positively correlated with both grade of BMF and extent of leukemic cell infiltration in the marrow. TGF-β likely plays a dual role in promoting myelofibrosis and myeloproliferation, both of which are the bone marrow morphologic hallmark of MF. AVID200 is a drug that targets TGF-β1 and TGF-β3. The study team hypothesizes that inhibiting the TGF-β signaling pathway in MF will decrease the fibrogenic stimuli leading to myelofibrosis and concomitantly interrupt myeloproliferation and restore normal hematopoiesis. This is a first in human, open-label, multicenter, Phase I/Ib trial of AVID200. Patients must have intermediate-2 or higher primary myelofibrosis (PMF), post-essential thrombocythemia or polycythemia-vera related MF (Post ET/PV MF). This study will enroll up to 24 patients. AVID200 is delivered by IV infusion on day 1 of each 3 week cycle.

Detailed description

This is a first in human, open-label, multicenter, Phase I/Ib trial of AVID200. To date, there is no therapy for MF evaluated in the clinic that clearly demonstrates the ability to target the malignant HSC and result in effective and reproducible bone marrow morphologic, cytogenetic and molecular responses. Medicinal therapies that result in disease course modification are urgently needed in this chronic and progressive myeloid malignancy. TGF-β likely plays a dual role in promoting myelofibrosis and myeloproliferation, both of which are the bone marrow morphologic hallmark of MF. The study team proposes that inhibiting the TGF-β signaling pathway in MF will decrease the fibrogenic stimuli leading to myelofibrosis and concomitantly interrupt myeloproliferation and restore normal hematopoiesis. AVID200 is a fusion protein containing TGF-β receptor ectodomains fused to a human Fc IgG domain. AVID200 is a potent TGFβ trap with antibody-like properties which has pM potency against two of the three TGFβ ligands, TGFβ1 and β3.

Conditions

• Primary Myelofibrosis
• Post-essential Thrombocythemia Myelofibrosis
• Post-polycythemia Vera Myelofibrosis
• Post ET MF
• Post PV MF

Interventions

Type	Name	Description
DRUG	AVID200	dose cohorts of 21-day cycles

Timeline

• Start date: 2019-02-15
• Primary completion: 2022-05-16
• Completion: 2022-05-16
• First posted: 2019-03-29
• Last updated: 2023-02-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study