A First in Human Study of AUR 103 Calcium to Evaluate Safety, Pharmacokinetics and Pharmacodynamics

NCT05607199 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: AUR103-101
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 5

Brief Summary

A Phase I, Open Label, Dose-Escalation, First in Human (FIH) study evaluating the Safety, Pharmacokinetics, Pharmacodynamics and Efficacy of AUR103 Calcium in patients with relapsed advanced malignancies (BHARAT-1).

Conditions

Myelodysplastic Syndromes; Non Hodgkin Lymphoma; Solid Tumor, Adult; Acute Myeloid Leukemia

Keywords

CD 47 inhibitor

Outcome Measures

Primary Outcomes (1)

• Primary Outcome: Optimal Biological Dose (OBD)

  To determine the Optimal Biological Dose (OBD) and evaluate the overall safety profile of single agent AUR103 Calcium in patients with relapsed advanced malignancies

  up to 16 weeks

Secondary Outcomes (6)

• Pharmacokinetics: Area under the curve, 0 to last

  Day 1 and Day 15

• Pharmacokinetics: Area under the curve, 0 to infinity

  Day 1 and Day 15

• Pharmacokinetics: Maximum concentration

  Day 1 and Day 15

• Pharmacokinetics: Time to Maximum concentration

  Day 1 and Day 15

• Pharmacokinetics: Terminal elimination half life

  Day 1 and Day 15

Other Outcomes (8)

• Pharmacodynamics: MCP-1 biomarker levels

  Day 1, Day 8, Day 15

• Pharmacodynamics: MCP-3 biomarker levels

  Day 1, Day 8, Day 15

• Pharmacodynamics: MIP-1 alpha biomarker levels

  Day 1, Day 8, Day 15

Study Arms (1)

AUR103, 25mg to 400mg

EXPERIMENTAL

Currently planned dose levels in Part 1 are 25 mg BID, 50 mg BID, 100 mg BID, 200 mg BID and 400 mg BID

Drug: AUR103

Interventions

AUR103 DRUG

Twice Daily

Also known as: AUR 103 Calcium

AUR103, 25mg to 400mg

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provide signed and dated informed consent and agree to comply with all study related activities.
• Male or female patients aged ≥ 18 years.
• Patients have to meet the following criteria for each of the respective parts of the study:
• Part 1:
• Pathological diagnosis of a solid tumor. Standard curative or life prolonging measures do not exist and patient must have exhausted all effective therapies, available locally. At a minimum, patients should have received at least 2 lines of therapy in the metastatic setting.
• Part 2A and 2B:
• Diagnosis of Acute myeloid leukemia (AML) according to the World Health Organization (WHO 2016, Appendix B) criteria. OR Myelodysplastic syndrome (MDS) according to the WHO classification (WHO 2016, Appendix B). Patients with relapsed / refractory AML (patients should have received at least one line of previous therapy and be eligible for single agent Azacitidine) or Intermediate / High-Risk / Very High-Risk Myelodysplastic syndrome (MDS) with IPSS-R score greater than 3.5, by IPSS - R criterion (Appendix C) who are eligible to receive AZA.
• Part 3A and 3B:
• Patients of CD20+ B cell NHL, who are refractory or relapsed after at least two previous lines of therapy Patients must not have any curative or life prolonging option and must not require immediate cytoreductive therapy Patients with histological sub-types of follicular lymphoma, marginal zone lymphoma (includes nodal marginal zone, splenic marginal zone and extra-nodal marginal zone of MALT tissue), mantle cell lymphoma, diffuse large B cell lymphoma, histologically transformed indolent lymphomas to DLBCL, high-grade B cell lymphomas and Primary Mediastinal Large B cell Lymphoma.
• Patients with indolent lymphomas (e.g., follicular lymphoma, marginal zone lymphoma or mantle cell lymphoma) must have conventional criterion, such as GELF criterion14
• , for requiring treatment Single agent Rituximab is a viable treatment alternative for the patient. Please refer to Appendix F for a detailed list of drugs/previous treatments. Note: The list is not exhaustive and not every treatment may be available locally.
• Patients with respective NHL subtypes should have received the following treatments Sub-Type of CD20+ B Cell Lymphoma : Follicular Lymphoma
• Previous Treatments :
• Patient must have received treatment with chemotherapy and CD20 antibody previously Patients must have received at least two lines of therapy previously and be eligible to receive Rituximab Sub-Type of CD20+ B Cell Lymphoma : Nodal Marginal Zone Lymphoma or Splenic Marginal Zone Lymphoma
• Previous Treatments:

You may not qualify if:

• Systemic anti-cancer therapy, such as chemotherapy, or biological therapy, immunomodulatory drug therapy, received within the past 28 days or 5 half-lives, whichever is shorter, from the Cycle 1 Day 1 of the study. Concomitant use of prednisone or medroxyprogesterone is allowed. In Part 1, Patients with CRPC (castrate resistant prostate cancer) should continue to receive ongoing medical castration with LHRH analogues, and such patients are allowed.
• Acute promyelocytic leukemia (AML M3 subtype).
• Patients eligible for intensive chemotherapy for AML (such as the 3 + 7 regimen).
• CML in blast crisis (i.e., patients with known bcr-abl positive disease).
• Presence of an acute or chronic toxicity resulting from prior anti cancer treatment, with the exception of alopecia or nail changes, that has not resolved to Grade Less than 1, as determined by NCI CTCAE v 5.0 (Appendix G).
• Definitive Radiotherapy within the last 21 days of Cycle 1 Day 1 (limited field palliative radiation is allowed and no restrictions during the screening period or during the trial).
• Use of any investigational agent within 28 days or 5 half-lives (whichever is shorter) prior to Cycle 1 Day 1.
• Known symptomatic or untreated or recently treated (Less than 6 months of screening) central nervous system (CNS) metastases or CNS lymphoma or CNS leukemia. Patients with previously treated (greater than 6 months of screening) CNS metastases or CNS lymphoma or CNS leukemia and are now stable and asymptomatic, from CNS perspective, are allowed.
• Major surgery Less than 28 days from Cycle 1 Day 1 (major surgery is defined as a procedure requiring general anesthesia).
• Known to be human immunodeficiency virus (HIV) positive or have an acquired immunodeficiency syndrome-related illness.
• Known active or chronic hepatitis B or hepatitis C infection.
• Uncontrolled congestive heart failure (New York Heart Association \[NYHA\] Class 2-4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, or transient ischemic attack, or pulmonary embolism within 3 months prior to Cycle 1 Day 1
• Ongoing cardiac dysrhythmias requiring treatment of any gradeor treatment of cardiac dysrhythmias in past 3 months, before Cycle 1 Day 1.
• The QTcF (corrected QT interval Fridericia method) value in the screening ECG greater than 450 ms in males and greater than 460 ms in females.
• Previous allogeneic stem cell or bone marrow transplantation

Sponsors & Collaborators

• Aurigene Discovery Technologies Limited: lead

Study Sites (5)

Unique Hospital

Surat, Gujarat, 395002, India

Location

Kiran Multi Super Specialty Hospital

Surat, Gujarat, 395004, India

Location

K R Hospital

Mysore, Karnataka, 570001, India

Location

Grant Medical Foundation Ruby Hall Clinic

Pune, Maharashtra, 411001, India

Location

All India Institute of Medical Sciences

Delhi, National Capital Territory of Delhi, 10029, India

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Lymphoma, Non-Hodgkin

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Akhil Kumar, MD

  Head Clinical Development

  STUDY DIRECTOR

Study Design

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

Model Details: Dose Escalation "3+3" Design

Study Record Dates

• First Submitted: October 21, 2022
• First Posted: November 7, 2022
• Study Start: September 16, 2022
• Primary Completion: November 27, 2024
• Study Completion: November 27, 2024
• Last Updated: April 17, 2026

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

IN (5)