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 (ODYSSEY)

First-In-Human, Open Label, Dose Escalation Study to Evaluate Safety, PK and PD of ABD-3001 As Monotherapy in Relapsed/Refractory Acute Myeloid Leukemia or High/Very-high Risk Myelodysplastic Syndromes Patients, Ineligible for Intensive or New Generation Targeted Therapy.

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.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndromes; Acute Myeloid Leukemia, Adult
• Intervention / Treatment: Drug: ABD-3001; Drug: ABD-3001

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Guillaume MARTIN; Phone Number: +33 (4) 82 53 89 62; Email: guillaume.martin@a-biodesign.com
• Study Contact Backup: Name: Laurent BASSET; Phone Number: +33 (0)4 28 29 46 78; Email: laurent.basset@a-biodesign.com

Study Locations

• France
  • Marseille, France, 13005
    • Recruiting
    • Hopital de la Timone
    • Contact: Régis COSTELLO; Email: regis.costello@ap-hm.fr
  • Paris, France, 75475
    • Recruiting
    • Hopital Saint-Louis
    • Contact: Lina BENAJIBA; Email: lina.benajiba@aphp.fr
  • Pierre-Bénite, France, 69495
    • Recruiting
    • Centre Hospitalier Lyon Sud
    • Contact: Maël HEIBLIG; Email: mael.heiblig@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)
• Any condition deemed by the investigator to be likely to interfere with a subject's ability to participate in the clinical trial MAD specific exclusion criteria: Patients who have been part of SAD and have experienced a DLT.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Administration Dose (SAD) of ABD-3001; Dose escalation of 6 doses level using a 3+3 design.	Drug: 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.; Other Names: DIMATE; 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.; Other Names: DIMATE
Experimental: Multiple Administration Dose (MAD) of ABD-3001; 3 doses regimens in parallel during 3 cycles of 28 days	Drug: 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.; Other Names: DIMATE; 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.; Other Names: DIMATE

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SAD : Estimation of the Maximum Tolerated Dose (MTD) of ABD-3001 as well as the doses and frequencies to be explored during the MAD	The primary endpoint is to assess the recommended dose range to be tested during the MAD by evaluation of incidence of patients who experienced Dose Limiting Toxicities (DLTs). according to CTCAE v5.0. The recommendation for doses to be tested during the MAD will be determined using all available data, which will include Dose Limiting Toxicities (DLTs), MTD if it has been reached, and other toxicities, signs of anti-leukemic activity, pharmacokinetic and pharmacodynamic characteristics.	7 days for SAD part
MAD : To evaluate the safety, tolerability and to define a recommended dose range for further trials.	To assess the impact of ABD-3001 on safety and on its tolerability by evaluating: Incidence of Adverse Events as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0 Nov. 27, 2017)), timing, seriousness, and relationship to ABD-3001 either observed by the investigator during physical examination, or reported spontaneously by the patient,; Incidence of laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0 Nov. 27, 2017), and timing.	3 months for MAD part.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SAD : To evaluate the overall safety and tolerability profile of ABD-3001	To assess the impact of ABD-3001 on safety and on its tolerability by evaluating: Incidence of Adverse Events as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0 Nov. 27, 2017)), timing, seriousness, and relationship to ABD-3001 either observed by the investigator during physical examination, or reported spontaneously by the patient,; Incidence of laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE v5.0 Nov. 27, 2017), and timing,	7 days for SAD part
SAD: To assess the pharmacokinetic (PK) parameters of ABD-3001	Maximum concentration (Cmax) of DIMATE and metabolites (CEY1410/H11)	7 days for SAD part
SAD: To assess the pharmacokinetic (PK) parameters of ABD-3001	Time to maximum concentration (Tmax)	7 days for SAD part
SAD: To assess the pharmacokinetic (PK) parameters of ABD-3001	Area Under the plasma Concentration versus time curve (AUC)	7 days for SAD part
SAD: To assess the pharmacokinetic (PK) parameters of ABD-3001	Elimination half-life.	7 days for SAD part
MAD : 1. To assess the pharmacokinetic (PK) parameter of multiple administration of ABD-3001.	PK parameter assessment: maximum concentration (Cmax) of DIMATE and metabolites (CEY1410/H11)	3 months for MAD part.
MAD : 2. To assess the pharmacokinetic (PK) parameter of multiple administration of ABD-3001.	PK parameter assessment: time to maximum concentration (Tmax)	3 months for MAD part.
MAD : 3. To assess the pharmacokinetic (PK) parameter of multiple administration of ABD-3001.	PK parameter assessment: Area Under the plasma Concentration versus time curve (AUC)	3 months for MAD part.
MAD : 4. To assess the pharmacokinetic (PK) parameter of multiple administration of ABD-3001.	PK parameter assessment: elimination half-life.	3 months for MAD part.
MAD : 1. To assess the pharmacodynamic (PD) parameter of multiple administration of ABD-3001.	PD parameter assessment: ALDH activity measurement in red blood cells	3 months for MAD part.
MAD : 2. To assess the pharmacodynamic (PD) parameter of multiple administration of ABD-3001.	PD parameter assessment: JUNK protein phosphorylation in plasma.	3 months for MAD part.
MAD : To evaluate the anti-leukemic activity as assessed by overall response rate (ORR: complete response [CR] + complete response with incomplete hematopoiesis [CRi] + morphologic leukemia-free state [MFLS] + partial response [PR])	To assess the potential preliminary evidence of anti-leukemia activity at each cycle using response criteria in AML without MRD assessment as defined by ELN 2022	3 months for MAD part.
MAD: To evaluate the duration of ORR.	To assess duration of ORR.	3 months for MAD part.
MAD: To evaluate Event free survival (EFS) and overall survival (OS) rates at 3-months and 6-months after the end of treatment	To assess the Event Free Survival and the Overall Survival as defined by ELN2022 until 6-months after end of treatment.	3 months for MAD part.
MAD: To assess the PRO-QoL during the treatment.	To assess the impact of ABD-3001 on quality of life according QLQ-C30 questionnaire at D1 of each cycle and at the end of treatment.	3 months for MAD part.

Collaborators and Investigators

• Sponsor: Advanced BioDesign
• Investigators: Study Director: Laurent BASSET, Advanced BioDesign

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 17, 2022
• First Submitted That Met QC Criteria: October 31, 2022
• First Posted (Actual): November 1, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 17, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: First in Human; Myelodysplastic syndromes; Acute Myeloid Leukemia, Adult; ABD-3001
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplasms by Histologic Type; Disease; Hematologic Diseases; Precancerous Conditions; Bone Marrow Diseases; Syndrome; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Myelodysplastic Syndromes
• Other Study ID Numbers: ABD3001CLIN1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No