RECRUITING

A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

WP44714 is a Phase I/II, open-label, non-randomized, global, multicenter trial consisting of two parts: * Part 1 is a multiple-ascending dose (MAD) study in adult and adolescent male participants with severe or moderate hemophilia A with or without factor VIII (FVIII) inhibitors. * Part 2 is a multiple-dose study in pediatric male participants with severe or moderate hemophilia A with or without FVIII inhibitors. The overall aim of the study is to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy of NXT007.

Official Title

A Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A

Quick Facts

Study Start:2023-09-21

Study Completion:2032-06-16

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05987449

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:2 Years to 59 Years

Sexes Eligible for Study:MALE

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* Diagnosis of severe (Factor VIII \[FVIII\] coagulant activity \<1 IU/dL) or moderate (FVIII coagulant activity ≥1 IU/dL and ≤5 IU/dL) congenital hemophilia A with or without inhibitors against FVIII * Participants with FVIII inhibitors: participants using recombinant activated factor VII (rFVIIa) or willing to switch to rFVIIa as primary bypassing agent for the treatment of breakthrough bleeds, trauma, or procedures * Historic local FVIII inhibitor test results being available during screening to confirm any previous inhibitor history and current status * Participants who previously successfully completed immune tolerance induction (ITI) must have done so at least 5 years before screening and must have no evidence of inhibitor recurrence (permanent or temporary) since. FVIII tolerance defined as \<0.6 Bethesda unit (BU)/mL (\<1.0 BU/mL only for laboratories with an historical sensitivity cutoff for inhibitor detection of 1.0 BU/mL) and in vivo recovery \>66% * Documentation of number and type of bleeding episodes in the last 24 weeks prior to enrollment * Adequate hematologic function, defined as platelet count ≥100,000 cells/μL and hemoglobin ≥11 g/dL at the time of screening * Adequate hepatic function defined as total bilirubin ≤1.5× age-adapted upper limit of normal (ULN) (excluding Gilbert syndrome) and both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3× age-adapted ULN at the time of screening, and no clinical signs or known laboratory/radiographic evidence consistent with cirrhosis. For patients with Gilbert syndrome, bilirubin should be \<4 mg/dL or 68.4 umol/L at the time of screening. * For Part 1 only: Adequate renal function, defined as serum creatinine ≤2.5× age-adapted ULN and calculated creatinine clearance ≥30 mL/min by Cockroft-Gault formula * For Part 2 only: Adequate renal function, defined as serum creatinine ≤1.5× age-adapted ULN. When the serum creatinine is ≥1.5× ULN, creatinine clearance by Bedside Schwartz formula must be \>70 mL/min/1.73m\^2. * Willingness and ability to comply with schedules visits, treatment plans, laboratory tests, and other study procedures	* Inherited or acquired bleeding disorders other than congenital hemophilia A * Ongoing or planned ITI therapy * Previous or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or signs of thromboembolic disease * At high risk for thrombotic microangiopathy (TMA), including past personal or family history of TMA, in the investigator's judgment * For Part 1 only: Personal history of ischemic heart disease, cerebrovascular disease, or diabetes mellitus * For Part 1 only: Strong family history of ischemic heart disease or cerebrovascular disease (i.e., first degree relatives such as parents, full siblings, or children): male relatives diagnosed under the age of 55 years and females under the age of 65 years * For Part 1 only: Previous or concomitant malignancies or leukemia * Other conditions (e.g., autoimmune conditions such as Systemic Lupus erythematosus and other systemic inflammatory disorders) that may currently increase the risk of bleeding or thrombosis * History of clinically significant allergies * Receipt of any of the following: * Protein C activity, protein S free antigen, or anti-thrombin III activity levels below the lower limit of the reference range at screening * Known HIV infection with CD4 counts \<200 cells/μL * History of severe allergic or anaphylactic reactions to monoclonal antibody therapy and to chimeric or humanized antibodies or fusion proteins * Known hypersensitivity to Chinese hamster ovary cell products or to excipient content * History or presence of an abnormal ECG that is deemed clinically significant, (e.g., complete left bundle branch block, second- or third -degree atrioventricular heart block), including atrial fibrillation or evidence of prior myocardial infarction * QT interval corrected through use of Fridericia's formula (QTcF) \>450 ms demonstrated by at least two ECGs \>30 minutes apart * History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome * Current treatment with medications that are well known to prolong the QT interval

Inclusion Criteria

Exclusion Criteria

* Diagnosis of severe (Factor VIII \[FVIII\] coagulant activity \<1 IU/dL) or moderate (FVIII coagulant activity ≥1 IU/dL and ≤5 IU/dL) congenital hemophilia A with or without inhibitors against FVIII
* Participants with FVIII inhibitors: participants using recombinant activated factor VII (rFVIIa) or willing to switch to rFVIIa as primary bypassing agent for the treatment of breakthrough bleeds, trauma, or procedures
* Historic local FVIII inhibitor test results being available during screening to confirm any previous inhibitor history and current status
* Participants who previously successfully completed immune tolerance induction (ITI) must have done so at least 5 years before screening and must have no evidence of inhibitor recurrence (permanent or temporary) since. FVIII tolerance defined as \<0.6 Bethesda unit (BU)/mL (\<1.0 BU/mL only for laboratories with an historical sensitivity cutoff for inhibitor detection of 1.0 BU/mL) and in vivo recovery \>66%
* Documentation of number and type of bleeding episodes in the last 24 weeks prior to enrollment
* Adequate hematologic function, defined as platelet count ≥100,000 cells/μL and hemoglobin ≥11 g/dL at the time of screening
* Adequate hepatic function defined as total bilirubin ≤1.5× age-adapted upper limit of normal (ULN) (excluding Gilbert syndrome) and both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3× age-adapted ULN at the time of screening, and no clinical signs or known laboratory/radiographic evidence consistent with cirrhosis. For patients with Gilbert syndrome, bilirubin should be \<4 mg/dL or 68.4 umol/L at the time of screening.
* For Part 1 only: Adequate renal function, defined as serum creatinine ≤2.5× age-adapted ULN and calculated creatinine clearance ≥30 mL/min by Cockroft-Gault formula
* For Part 2 only: Adequate renal function, defined as serum creatinine ≤1.5× age-adapted ULN. When the serum creatinine is ≥1.5× ULN, creatinine clearance by Bedside Schwartz formula must be \>70 mL/min/1.73m\^2.
* Willingness and ability to comply with schedules visits, treatment plans, laboratory tests, and other study procedures

* Inherited or acquired bleeding disorders other than congenital hemophilia A
* Ongoing or planned ITI therapy
* Previous or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing) or signs of thromboembolic disease
* At high risk for thrombotic microangiopathy (TMA), including past personal or family history of TMA, in the investigator's judgment
* For Part 1 only: Personal history of ischemic heart disease, cerebrovascular disease, or diabetes mellitus
* For Part 1 only: Strong family history of ischemic heart disease or cerebrovascular disease (i.e., first degree relatives such as parents, full siblings, or children): male relatives diagnosed under the age of 55 years and females under the age of 65 years
* For Part 1 only: Previous or concomitant malignancies or leukemia
* Other conditions (e.g., autoimmune conditions such as Systemic Lupus erythematosus and other systemic inflammatory disorders) that may currently increase the risk of bleeding or thrombosis
* History of clinically significant allergies
* Receipt of any of the following:
* Protein C activity, protein S free antigen, or anti-thrombin III activity levels below the lower limit of the reference range at screening
* Known HIV infection with CD4 counts \<200 cells/μL
* History of severe allergic or anaphylactic reactions to monoclonal antibody therapy and to chimeric or humanized antibodies or fusion proteins
* Known hypersensitivity to Chinese hamster ovary cell products or to excipient content
* History or presence of an abnormal ECG that is deemed clinically significant, (e.g., complete left bundle branch block, second- or third -degree atrioventricular heart block), including atrial fibrillation or evidence of prior myocardial infarction
* QT interval corrected through use of Fridericia's formula (QTcF) \>450 ms demonstrated by at least two ECGs \>30 minutes apart
* History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
* Current treatment with medications that are well known to prolong the QT interval

Contacts and Locations

Study Contact

Reference Study ID Number: WP44714 https://forpatients.roche.com/

CONTACT

888-662-6728 (U.S. Only)

global-roche-genentech-trials@gene.com

Principal Investigator

Clinical Trials

STUDY_DIRECTOR

Hoffmann-La Roche

Study Locations (Sites)

UC Davis Cancer Center

Sacramento, California, 95817

United States

Georgetown Uni Medical Center

Washington, District of Columbia, 20007

United States

Indiana Hemophilia & Thrombosis center

Indianapolis, Indiana, 46260

United States

University of Iowa Hospitals and Clnics Dept of Pediatrics

Iowa City, Iowa, 52242

United States

Collaborators and Investigators

Sponsor: Hoffmann-La Roche

Clinical Trials, STUDY_DIRECTOR, Hoffmann-La Roche

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-09-21

Study Completion Date2032-06-16

Study Record Updates

Study Start Date2023-09-21

Study Completion Date2032-06-16

Terms related to this study

Additional Relevant MeSH Terms

Hemophilia A