First-in-human Study Aiming to Characterize the Safety, Tolerability, Pharmacokinetic and Preliminary Signs of Activity of ABD-3001 in Refractory or Relapsed AML and High Risk MDS Adult Patients

NCT ID: NCT05601726

Last Updated: 2025-01-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-08
• Study Completion Date: 2026-12-31

Brief Summary

This First In Human (FIH) study is a prospective, open-label, multicenter, Phase 1 study, with a dose escalation design, followed by an optimized design. It will consist in a Single Ascending Dose (SAD) part and a Multiple Ascending Dose (MAD) part.

Detailed Description

This FIH study combines, in patients with primary refractory or relapsed AML patients and in patients with high risk MDS a Single Ascending Dose (SAD) part (Part A) and a Multiple Ascending Dose (MAD) part (Part B).

The objective of the SAD phase is to explore a wide range of dose administered as a single and fixed 4-hours intravenous infusion in order to select a dose and a dosing frequency (determined using pharmacokinetic and pharmacodynamics parameters).

The objective of the MAD is to elucidate the pharmacokinetic (PK) and pharmacodynamics (PD) of multiple doses of ABD-3001. The dose levels and dosing intervals (i.e., time between consecutive doses) will be selected as those that are predicted to be safe from the SAD. Dose levels and dosing frequency will be derived from data obtained during the SAD.

Conditions

Acute Myeloid Leukemia, Adult; Myelodysplastic Syndromes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single Administration Dose (SAD) of ABD-3001

Dose escalation of 6 doses level using a 3+3 design.

Group Type: EXPERIMENTAL

ABD-3001

Intervention Type: DRUG

Each patient will receive a fixed 4 hours-intravenous infusion dose of ABD-3001 once or twice a week.

For SAD : The first dose of the first cohort will receive an estimated infusion dose of 18 mg/m² at Day 1. Subsequent cohorts will be given the following doses: 54 mg/m², 135 mg/m², 270 mg/m², 405 mg/m², 540 mg/m².

Multiple Administration Dose (MAD) of ABD-3001

3 doses regimens in parallel during 3 cycles of 28 days

Group Type: EXPERIMENTAL

ABD-3001

Intervention Type: DRUG

For MAD :

Based on all data gathered during the SAD including safety, PK and preliminary efficacy data, up to three doses were selected in accordance with the Safety review Committee (SRC). A dosage optimization analysis was performed at the end of the SAD cohort 6 using population pharmacokinetic modelling to set the optimal frequency of infusion per week for each selected dose to achieve sustained exposition throughout the treatment period. Based on this analysis, the Sponsor, in agreement with the SRC, defined 3 doses regimens that will be set up in parallel, with infusion of ABD-3001 once or twice a week during 3 cycles of 28 days.

Interventions

ABD-3001

Each patient will receive a fixed 4 hours-intravenous infusion dose of ABD-3001 once or twice a week.

For SAD : The first dose of the first cohort will receive an estimated infusion dose of 18 mg/m² at Day 1. Subsequent cohorts will be given the following doses: 54 mg/m², 135 mg/m², 270 mg/m², 405 mg/m², 540 mg/m².

Intervention Type: DRUG

ABD-3001

For MAD :

Based on all data gathered during the SAD including safety, PK and preliminary efficacy data, up to three doses were selected in accordance with the Safety review Committee (SRC). A dosage optimization analysis was performed at the end of the SAD cohort 6 using population pharmacokinetic modelling to set the optimal frequency of infusion per week for each selected dose to achieve sustained exposition throughout the treatment period. Based on this analysis, the Sponsor, in agreement with the SRC, defined 3 doses regimens that will be set up in parallel, with infusion of ABD-3001 once or twice a week during 3 cycles of 28 days.

Intervention Type: DRUG

Other Intervention Names

DIMATE; DIMATE

Eligibility Criteria

Inclusion Criteria

• Patients with relapsed/refractory Acute Myeloid Leukemia (AML) after failing at least one therapy regimen and a salvage treatment or are not eligible for salvage treatment regimens including targeted therapy
• Patients with relapsed/refractory Myelodysplastic syndrome (MDS) ineligible for salvage treatment who are diagnosed high-risk and very high-risk using Revised International Prognostic Scoring System (IPSS-R) prognostic risk categorization
• Patients not eligible to alloSCT
• Negative blood or serum/urine pregnancy test

Exclusion Criteria

• Patients with acute myeloid leukemia (AML) with Inv(16) MYH11-CBF-Beta or t(8;21) AML-ETO RUNX1-RUNX1 or (PML/RARA) karyotype abnormalities and eligible to targeted therapies
• Participants with clinical symptoms suggestive of active central nervous system (CNS) leukemia or known CNS leukemia
• Ongoing immunosuppressive treatment
• Hematopoietic stem cell transplantation (HSCT) performed within 3 months prior to study Visit 1
• Active infection requiring intravenous anti-infectious treatment during the screening period
• Life-threatening illnesses other than the studied one, uncontrolled medical conditions or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety or interfere with the patient's ability to comply with the study activities
• Anti-tumor therapy within 14 days of study Visit 1
• Prior participation in an interventional investigational clinical study (drug or medical device) within 21 days of study Visit 1
• Radiotherapy within 28 days prior to study Visit 1
• Current history of seropositivity to human immunodeficiency virus (HIV) or infection with active hepatitis C virus (HCV) or active hepatitis B virus (HBV) or active SARS-CoV-2 (Covid-19) or Syphilis, or Cytomegalovirus (CMV), or Epstein-Barr virus (EBV), or Human T-Lymphotropic Virus (HTLV1)
• History of other malignancy in the last 12 months prior to study Visit 1
• Other active solid tumor
• Subjects with New York Heart Association (NYHA) Class III or IV congestive heart failure or Left Ventricular Ejection Fraction (LVEF) <50% attested by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan within 28 days of C1D1 prior to study Visit 1 (Day 1, start of study therapy)
• Subjects with a history of myocardial infarction within the last 3 months prior to study Visit 1 (Day 1, start of study therapy)
• Subjects with heart-rate corrected QT (QTc) interval ≥450 ms or other factors that increase the risk of QT prolongation or arrhythmic events
• Major surgery within 4 weeks prior to study Visit 1 (Day 1, start of study therapy)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Advanced BioDesign

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Laurent BASSET

Role: STUDY_DIRECTOR

Advanced BioDesign

Locations

Hôpital de la Timone

Marseille, France, France

Site Status: RECRUITING

Hôpital Saint-Louis

Paris, France, France

Site Status: RECRUITING

Centre Hospitalier Lyon Sud

Pierre-Bénite, France, France

Site Status: RECRUITING

Countries

France

Central Contacts

Guillaume MARTIN

Role: CONTACT

guillaume.martin@a-biodesign.com

+33 (4) 82 53 89 62

Laurent BASSET

Role: CONTACT

laurent.basset@a-biodesign.com

+33 (0)4 28 29 46 78

Facility Contacts

Régis COSTELLO

Role: primary

regis.costello@ap-hm.fr

Lina BENAJIBA

Role: primary

lina.benajiba@aphp.fr

Maël HEIBLIG

Role: primary

mael.heiblig@chu-lyon.fr

References

Venton G, Colle J, Tichadou A, Quessada J, Baier C, Labiad Y, Perez M, De Lassus L, Loosveld M, Arnoux I, Abbou N, Ceylan I, Martin G, Costello R. Reactive oxygen species and aldehyde dehydrogenase 1A as prognosis and theragnostic biomarker in acute myeloid leukaemia patients. J Cell Mol Med. 2024 Oct;28(19):e70011. doi: 10.1111/jcmm.70011.

Reference Type: DERIVED

PMID: 39392121 (View on PubMed)

Other Identifiers

ABD3001CLIN1

Identifier Type: -

Identifier Source: org_study_id