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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hemophilia A
• Intervention / Treatment: Drug: NXT007

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: WP44714 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6H 3N1
      • Recruiting
      • British Columbia Children's Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Recruiting
      • Hamilton Health Sciences Corporation
• Italy
  • Lombardy
    • Milan, Lombardy, Italy, 20122
      • Recruiting
      • IRCCS Ca' Granda Ospedale Maggiore Policlinico
    • Rozzano (MI), Lombardy, Italy, 20089
      • Recruiting
      • Istituto Clinico Humanitas
• New Zealand
  • Auckland, New Zealand, 1023
    • Recruiting
    • Auckland Cancer Trial Centre
• Poland
  • Gda?sk, Poland, 80-214
    • Recruiting
    • Uniwersyteckie Centrum Kliniczne
  • Warsaw, Poland, 02-776
    • Recruiting
    • Instytut Hematologii i Transfuzjologii
• Spain
  • Madrid, Spain, 28046
    • Recruiting
    • Hospital Universitario La Paz
  • Málaga, Spain, 29010
    • Active, not recruiting
    • Hospital Regional Universitario Carlos Haya
  • Barcelona
    • Esplugues de Llobregat, Barcelona, Spain, 08950
      • Recruiting
      • Hospital Sant Joan de Déu
• United States
  • California
    • Sacramento, California, United States, 95817
      • Recruiting
      • UC Davis Cancer Center
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • Withdrawn
      • Georgetown Uni Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Recruiting
      • Indiana Hemophilia & Thrombosis center
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa Hospitals and Clnics Dept of Pediatrics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion 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

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
• 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:

  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; v) Use of systemic immunomodulators (e.g., interferon or rituximab) at enrollment or planned use during the study, with the exception of anti-retroviral therapy to treat HIV.

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Cohort 1 - NXT007 Dose Level 1 (Low)	Drug: NXT007; 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.; Other Names: RO7589655; RG6512; Zemocimig
Experimental: Part 1: Cohort 2 - NXT007 Dose Level 2	Drug: NXT007; 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.; Other Names: RO7589655; RG6512; Zemocimig
Experimental: Part 1: Cohort 3 - NXT007 Dose Level 3	Drug: NXT007; 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.; Other Names: RO7589655; RG6512; Zemocimig
Experimental: Part 1: Cohort 4 - NXT007 Dose Level 4	Drug: NXT007; 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.; Other Names: RO7589655; RG6512; Zemocimig
Experimental: Part 1: Cohort 5 - NXT007 Dose Level 5 (High)	Drug: NXT007; 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.; Other Names: RO7589655; RG6512; Zemocimig
Experimental: Part 2: Cohort A - NXT007	Drug: NXT007; 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.; Other Names: RO7589655; RG6512; Zemocimig

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and Severity of Adverse Events, with Severity Determined According to National Cancer Institute Common Terminology Criteria for Adverse Events Grading Scale		From Baseline until study completion or discontinuation (up to 7.5 years)
Number of Participants with at Least One Clinical Laboratory Test Abnormality for Hematology Parameters		From Baseline until study completion or discontinuation (up to 7.5 years)
Number of Participants with at Least One Clinical Laboratory Test Abnormality for Blood Chemistry Parameters		From Baseline until study completion or discontinuation (up to 7.5 years)
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.	From Baseline until study completion or discontinuation (up to 7.5 years)
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.	From Baseline until study completion or discontinuation (up to 7.5 years)

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum Observed Plasma Concentration (Cmax) of NXT007 After the First Dose	At prespecified timepoints from Day 1 to Day 15
Time to Maximum Observed Plasma Concentration (tmax) of NXT007 After the First Dose	At prespecified timepoints from Day 1 to Day 15
Area Under the Plasma Concentration-Time Curve (AUC) of NXT007 After the First Dose	At prespecified timepoints from Day 1 to Day 15
Number of Participants Testing Positive for Anti-Drug Antibodies Against NXT007 at Baseline and During Treatment with Study Drug	Baseline (predose on Day 1) and from first dose of study drug until study completion or discontinuation (up to 7.5 years)
Number of Participants Testing Positive for Anti-Factor VIII Inhibitors at Baseline and During Treatment with Study Drug	Baseline (predose on Day 1) and from first dose of study drug until study completion or discontinuation (up to 7.5 years)
Model-Based Annualized Bleeding Rate for Treated Bleeds	From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Mean Calculated Annualized Bleeding Rate for Treated Bleeds	From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Median Calculated Annualized Bleeding Rate for Treated Bleeds	From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Model-Based Annualized Bleeding Rate for All Bleeds	From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Mean Calculated Annualized Bleeding Rate for All Bleeds	From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Median Calculated Annualized Bleeding Rate for All Bleeds	From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Model-Based Annualized Bleeding Rate for Treated Spontaneous Bleeds	From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Mean Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds	From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Median Calculated Annualized Bleeding Rate for Treated Spontaneous Bleeds	From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Model-Based Annualized Bleeding Rate for Treated Joint Bleeds	From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Mean Calculated Annualized Bleeding Rate for Treated Joint Bleeds	From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Median Calculated Annualized Bleeding Rate for Treated Joint Bleeds	From first dose of study drug until study completion or discontinuation (up to 7.5 years)
Plasma Concentration of NXT007 at Specified Timepoints	At prespecified timepoints from Week 1 to Week 23, every 28 days from Week 25 until Week 49, and every 12 weeks thereafter until study completion or discontinuation (up to 7.5 years)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2023
• Primary Completion (Estimated): June 16, 2030
• Study Completion (Estimated): June 16, 2030

Study Registration Dates

• First Submitted: August 4, 2023
• First Submitted That Met QC Criteria: August 4, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Hemophilia A
• Other Study ID Numbers: WP44714; 2023-503906-35-00 (Registry Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

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