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

Primary Purpose

Hemophilia A

Status
Recruiting
Phase
Phase 1
Locations
New Zealand
Study Type
Interventional
Intervention
NXT007
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemophilia A

Eligibility Criteria

12 Years - 59 Years (Child, Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria: Body weight ≥40 kilograms (kg) at screening 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 AST and ALT ≤3× age-adapted ULN at the time of screening, and no clinical signs or known laboratory/radiographic evidence consistent with cirrhosis Adequate renal function, defined as serum creatinine ≤2.5× age-adapted ULN and calculated creatinine clearance ≥30 mL/min by Cockroft-Gault formula Willingness and ability to comply with schedules visits, treatment plans, laboratory tests, and other study procedures Exclusion Criteria: 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 Personal history of ischemic heart disease, cerebrovascular disease, or diabetes mellitus 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, females under the age of 65 years 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 Previous or concomitant malignancies or leukemia Receipt of any of the following: i) An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration or normalization of targeted parameters (e.g., anti-thrombin), whichever is longer; ii) A non-hemophilia-related investigational drug within last 30 days or 5 half-lives, whichever is shorter; iii) Any other investigational drug currently being administered or planned to be administered; iv) Prior gene therapy or gene therapy planned to be administered. 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

Sites / Locations

  • Auckland Cancer Trial Centre; Ward 64, Auckland City Hospital,Recruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

NXT007 Dose Escalation

Arm Description

Outcomes

Primary Outcome Measures

Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Grading Scale
Number of Participants with at Least One Clinical Laboratory Test Abnormality for Hematology Parameters
Number of Participants with at Least One Clinical Laboratory Test Abnormality for Blood Chemistry Parameters
Number of Participants with at Least One Vital Sign Abnormality
The vital signs that will be assessed are body temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.
Number of Participants with at Least One Abnormality on Electrocardiogram (ECG) Recordings
The ECG parameters that will be assessed are heart rate, PR interval, QRS interval, QT interval, and QTcF inteval.

Secondary Outcome Measures

Plasma Concentration of NXT007 at Specified Timepoints
Maximum Observed Plasma Concentration (Cmax) of NXT007 After the First Dose
Time to Maximum Observed Plasma Concentration (tmax) of NXT007 After the First Dose
Area Under the Plasma Concentration-Time Curve (AUC) of NXT007 After the First Dose
Number of Participants Testing Positive for Anti-Drug Antibodies Against NXT007 at Baseline and During Treatment with Study Drug
Number of Participants Testing Positive for Anti-Factor VIII Inhibitors at Baseline and During Treatment with Study Drug
Model-Based Annualized Bleeding Rate for Treated Bleeds
Mean Calculated Annualized Bleeding Rate for Treated Bleeds
Median Calculated Annualized Bleeding Rate for Treated Bleeds
Model-Based Annualized Bleeding Rate for All Bleeds
Mean Calculated Annualized Bleeding Rate for All Bleeds
Median Calculated Annualized Bleeding Rate for All Bleeds
Model-Based Annualized Bleeding Rate for Treated Spontaneous Bleeds
Mean Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds
Median Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds
Model-Based Annualized Bleeding Rate for Treated Joint Bleeds
Mean Calculated Annualized Bleeding Rate for Treated Joint Bleeds
Median Calculated Annualized Bleeding Rate for Treated Joint Bleeds

Full Information

First Posted
August 4, 2023
Last Updated
October 6, 2023
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT05987449
Brief Title
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 21, 2023 (Actual)
Primary Completion Date
June 16, 2032 (Anticipated)
Study Completion Date
June 16, 2032 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Study WP44714 is a Phase I/II, open-label, non-randomized, global, multicenter, multiple-ascending dose (MAD) study in adult and adolescent male participants with severe or moderate hemophilia A with or without factor VIII (FVIII) inhibitors. The aim is to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy of multiple ascending doses of NXT007.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
NXT007 Dose Escalation
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
NXT007
Other Intervention Name(s)
RO7589655
Intervention Description
Participants will receive NXT007 administered subcutaneously (SC), 2 loading doses once every two weeks (Q2W) followed by once every 4 weeks (Q4W) maintenance doses based on the schedule.
Primary Outcome Measure Information:
Title
Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Grading Scale
Time Frame
From Baseline until study completion or discontinuation (up to 7.5 years)
Title
Number of Participants with at Least One Clinical Laboratory Test Abnormality for Hematology Parameters
Time Frame
From Baseline until study completion or discontinuation (up to 7.5 years)
Title
Number of Participants with at Least One Clinical Laboratory Test Abnormality for Blood Chemistry Parameters
Time Frame
From Baseline until study completion or discontinuation (up to 7.5 years)
Title
Number of Participants with at Least One Vital Sign Abnormality
Description
The vital signs that will be assessed are body temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.
Time Frame
From Baseline until study completion or discontinuation (up to 7.5 years)
Title
Number of Participants with at Least One Abnormality on Electrocardiogram (ECG) Recordings
Description
The ECG parameters that will be assessed are heart rate, PR interval, QRS interval, QT interval, and QTcF inteval.
Time Frame
From Baseline until study completion or discontinuation (up to 7.5 years)
Secondary Outcome Measure Information:
Title
Plasma Concentration of NXT007 at Specified Timepoints
Time Frame
At prespecified timepoints from Day 1 to Day 155, and every 28 days from Day 169 until study completion (up to 7.5 years)
Title
Maximum Observed Plasma Concentration (Cmax) of NXT007 After the First Dose
Time Frame
At prespecified timepoints from Day 1 to Day 15
Title
Time to Maximum Observed Plasma Concentration (tmax) of NXT007 After the First Dose
Time Frame
At prespecified timepoints from Day 1 to Day 15
Title
Area Under the Plasma Concentration-Time Curve (AUC) of NXT007 After the First Dose
Time Frame
At prespecified timepoints from Day 1 to Day 15
Title
Number of Participants Testing Positive for Anti-Drug Antibodies Against NXT007 at Baseline and During Treatment with Study Drug
Time Frame
Baseline (predose on Day 1) and from first dose of study drug until study completion or discontinuation (up to 7.5 years)
Title
Number of Participants Testing Positive for Anti-Factor VIII Inhibitors at Baseline and During Treatment with Study Drug
Time Frame
Baseline (predose on Day 1) and from first dose of study drug until study completion or discontinuation (up to 7.5 years)
Title
Model-Based Annualized Bleeding Rate for Treated Bleeds
Time Frame
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Title
Mean Calculated Annualized Bleeding Rate for Treated Bleeds
Time Frame
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Title
Median Calculated Annualized Bleeding Rate for Treated Bleeds
Time Frame
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Title
Model-Based Annualized Bleeding Rate for All Bleeds
Time Frame
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Title
Mean Calculated Annualized Bleeding Rate for All Bleeds
Time Frame
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Title
Median Calculated Annualized Bleeding Rate for All Bleeds
Time Frame
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Title
Model-Based Annualized Bleeding Rate for Treated Spontaneous Bleeds
Time Frame
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Title
Mean Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds
Time Frame
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Title
Median Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds
Time Frame
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Title
Model-Based Annualized Bleeding Rate for Treated Joint Bleeds
Time Frame
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Title
Mean Calculated Annualized Bleeding Rate for Treated Joint Bleeds
Time Frame
From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Title
Median Calculated Annualized Bleeding Rate for Treated Joint Bleeds
Time Frame
From first dose of study drug until study completion or discontinuation (up to 7.5 years)

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
59 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Body weight ≥40 kilograms (kg) at screening 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 AST and ALT ≤3× age-adapted ULN at the time of screening, and no clinical signs or known laboratory/radiographic evidence consistent with cirrhosis Adequate renal function, defined as serum creatinine ≤2.5× age-adapted ULN and calculated creatinine clearance ≥30 mL/min by Cockroft-Gault formula Willingness and ability to comply with schedules visits, treatment plans, laboratory tests, and other study procedures Exclusion Criteria: 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 Personal history of ischemic heart disease, cerebrovascular disease, or diabetes mellitus 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, females under the age of 65 years 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 Previous or concomitant malignancies or leukemia Receipt of any of the following: i) An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration or normalization of targeted parameters (e.g., anti-thrombin), whichever is longer; ii) A non-hemophilia-related investigational drug within last 30 days or 5 half-lives, whichever is shorter; iii) Any other investigational drug currently being administered or planned to be administered; iv) Prior gene therapy or gene therapy planned to be administered. 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Reference Study ID Number: WP44714 https://forpatients.roche.com/
Phone
888-662-6728 (U.S. Only)
Email
global-roche-genentech-trials@gene.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Auckland Cancer Trial Centre; Ward 64, Auckland City Hospital,
City
Auckland
ZIP/Postal Code
1023
Country
New Zealand
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
For eligible studies, qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). Roche's Global Policy on the Sharing of Clinical Information describes studies which are eligible for data sharing and how to request access (https://www.roche.com/innovation/process/clinical-trials/data-sharing/).

Learn more about this trial

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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