A Dose Escalation Study of FP-045 in Patients With Fanconi Anemia

A Multinational, Multicenter, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Activity of FP 045 in Patients With Fanconi Anemia (FusuciA Study)

This is a multi-center, Phase 1/2 study to determine the Optimal Biologic Dose (OBD) and to evaluate the safety, tolerability, PK, and preliminary activity of FP 045 when administered orally in young adult/adolescent and pediatric patients with Fanconi anemia. The study will enroll a total of 6 young adult/adolescent patients and a minimum of 8 and up to 12 pediatric patients with mild-moderate bone marrow failure who have not undergone hematopoietic cell transplant. This makes the total patient number between 14-18 total. Dose escalation will occur individually for each patient, within each age group. Each patient will receive each of 3 dose levels of FP 045 (intra-patient dose escalation), beginning with Dose Level 1, followed by Dose Levels 2 and 3. Each dose level will be administered for 28 days prior to escalation to the next higher dose level for that patient.

Study Overview

• Status: Recruiting
• Conditions: Fanconi Anemia
• Intervention / Treatment: Drug: FP-045

Detailed Description

Dose escalation will begin with young adult/adolescent patients. The initial two patients enrolled in the study will be > 15 years of age. These patients must complete the entire 28-day period of treatment at Dose Level 1 prior to additional young adult/adolescent patients being enrolled. All 6 young adult/adolescent patients must complete 28 days of treatment at Dose Level 1, and cumulative safety must be reviewed by the Safety Review Committee (SRC), prior to the enrollment of pediatric patients. The initial two pediatric patients enrolled will be > 6 years of age. These patients must complete the entire 28-day period of treatment at Dose Level 1 prior to additional pediatric patients being enrolled. A minimum of 8 and maximum of 12 pediatric patients will be enrolled to allow for at least 4 patients between the ages of 3-6.

Study assessments will be conducted at each visit. Patients will be observed closely for Dose Limiting Toxicity (DLT) during each dosing period. Any patient experiencing a DLT will have study drug interrupted and will not be allowed to escalate to the next higher dose level. The patient may resume treatment at one dose level lower once the DLT has resolved to baseline or to ≤ Grade 1 in severity. The MTD will be defined as the dose level immediately below the dose level at which DLT occurred. Patients requiring an interruption in treatment of > 3 weeks following a DLT will be withdrawn from the study. The MTD will be assessed separately for each individual patient.

Following the completion of dose escalation, each patient will continue treatment at either the highest dose or their individual MTD, and then transition to the OBD for their age group (once defined), for a total of 3 months. Patients failing to receive 75% of planned doses for reasons other than adverse effects may be replaced.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Bassem Elmankabadi, MD; Phone Number: 562 310-8718; Email: Bassem.elmankabadi@foreseepharma.com
• Study Contact Backup: Name: Yisheng Lee, MD, PhD; Phone Number: 408 823-4807; Email: yisheng.lee@foreseepharma.com

Study Locations

• United States
  • California
    • Palo Alto, California, United States, 94305
      • Recruiting
      • Lucille Packard Children's Hospital, Stanford University
      • Contact: Rajni Agarwal-Hashmi, M.D.; Phone Number: 650-497-0753
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • Masonic Cancer Center, University of Minnesota
      • Principal Investigator: Meera Srikanthan, MD
  • New York
    • New York, New York, United States, 10022
      • Recruiting
      • David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
      • Contact: Maria Cancio, M.D.; Phone Number: 212-639-8478; Email: canciom@mskcc.org
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • Not yet recruiting
      • St. Jude Childrens Research Hospital
      • Contact: Olivia McGregor; Email: Olivia.McGregor@STJUDE.ORG
      • Principal Investigator: Clifford Takemoto

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 23 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• male or female aged 3-25
• documented Fanconi anemia by chromosome breakage analysis
• females of child-bearing potential and males required to use highly effective birth control
• mild to moderate bone marrow failure with at least one cytopenia of > grade 1 severity

Exclusion Criteria:

• history of any malignancy except focal squamous cell or basal cell carcinoma of the skin or carcinoma in situ of cervix
• has myelodysplastic syndrome or acute leukemia per world health organization (WHO) criteria
• has history of any significant medical conditions
• has aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 5x upper limit of normal (ULN) or calculated creatinine clearance (Clcr) of < 50 mL/min
• has active Hepatitis B or C
• has an ongoing systemic infection
• requires a strong CYP3A4 inhibitor
• has had major surgery within 30 days
• Active graft versus host disease requiring systemic treatment
• Has a history of bone marrow or stem cell transplant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FP-045; The study will enroll a total of 6 young adult/adolescent patients progressing through three dose levels, followed by a minimum of 8 and up to 12 pediatric patients progressing through up to three dose levels.	Drug: FP-045; activator of aldehyde dehydrogenase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Optimal Biologic Dose (OBP) of FP-045	The OBP of FP-045 in adolescent and pediatric subjects	28 days x up to 3 doses
stabilizing or improving cytopenia in FA	Change from baseline in hemoglobin	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	Frequency of adverse events and serious adverse events	3-6 months
pharmacokinetic profile	Mean AUC of FP-045 by dose level	3- 6 months

Collaborators and Investigators

• Sponsor: Foresee Pharmaceuticals Co., Ltd.
• Investigators: Study Director: Susan Whitaker, Foresee Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2023
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: August 3, 2020
• First Submitted That Met QC Criteria: August 19, 2020
• First Posted (Actual): August 21, 2020

Study Record Updates

• Last Update Posted (Estimated): November 13, 2023
• Last Update Submitted That Met QC Criteria: November 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Bone Marrow Diseases; Hematologic Diseases; Genetic Diseases, Inborn; DNA Repair-Deficiency Disorders; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Renal Tubular Transport, Inborn Errors; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Anemia; Fanconi Syndrome; Fanconi Anemia
• Other Study ID Numbers: FP045C-19-001

Plan for Individual participant data (IPD)

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

Study Data/Documents

1. Study Protocol
   Information comments: clinicaltrials.gov
2. Statistical Analysis Plan
   Information comments: clinicaltrials.gov

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No