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

NCT05987449 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: WP447142023-503906-35-00
• Study Type: interventional
• Target: 60
• Locations: 6 countries
• Sites: 14

Brief Summary

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.

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (18)

• 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)

• 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)

Study Arms (6)

Part 1: Cohort 1 - NXT007 Dose Level 1 (Low)

EXPERIMENTAL

Drug: NXT007

Part 1: Cohort 2 - NXT007 Dose Level 2

EXPERIMENTAL

Drug: NXT007

Part 1: Cohort 3 - NXT007 Dose Level 3

EXPERIMENTAL

Drug: NXT007

Part 1: Cohort 4 - NXT007 Dose Level 4

EXPERIMENTAL

Drug: NXT007

Part 1: Cohort 5 - NXT007 Dose Level 5 (High)

EXPERIMENTAL

Drug: NXT007

Part 2: Cohort A - NXT007

EXPERIMENTAL

Drug: NXT007

Interventions

NXT007 DRUG

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.

Also known as: Zemocimig, RO7589655, RG6512

Part 1: Cohort 1 - NXT007 Dose Level 1 (Low); Part 1: Cohort 2 - NXT007 Dose Level 2; Part 1: Cohort 3 - NXT007 Dose Level 3; Part 1: Cohort 4 - NXT007 Dose Level 4; Part 1: Cohort 5 - NXT007 Dose Level 5 (High); Part 2: Cohort A - NXT007

Eligibility Criteria

• Age: 2 Years - 59 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (14)

UC Davis Cancer Center

Sacramento, California, 95817, United States

RECRUITING

Georgetown Uni Medical Center

Washington D.C., District of Columbia, 20007, United States

WITHDRAWN

Indiana Hemophilia & Thrombosis center

Indianapolis, Indiana, 46260, United States

RECRUITING

University of Iowa Hospitals and Clnics Dept of Pediatrics

Iowa City, Iowa, 52242, United States

RECRUITING

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3N1, Canada

RECRUITING

Hamilton Health Sciences Corporation

Hamilton, Ontario, L8N 3Z5, Canada

RECRUITING

IRCCS Ca' Granda Ospedale Maggiore Policlinico

Milan, Lombardy, 20122, Italy

RECRUITING

Istituto Clinico Humanitas

Rozzano (MI), Lombardy, 20089, Italy

RECRUITING

Auckland Cancer Trial Centre

Auckland, 1023, New Zealand

RECRUITING

Uniwersyteckie Centrum Kliniczne

Gda?sk, 80-214, Poland

RECRUITING

Instytut Hematologii i Transfuzjologii

Warsaw, 02-776, Poland

RECRUITING

Hospital Sant Joan de Deu

Esplugues de Llobregat, Barcelona, 08950, Spain

RECRUITING

Hospital Universitario la Paz

Madrid, 28046, Spain

RECRUITING

Hospital Regional Universitario Carlos Haya

Málaga, 29010, Spain

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Hemophilia A

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Central Study Contacts

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

CONTACT

888-662-6728 (U.S. Only); global-roche-genentech-trials@gene.com

Study Design

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

Study Record Dates

• First Submitted: August 4, 2023
• First Posted: August 14, 2023
• Study Start: September 21, 2023
• Primary Completion (Estimated): June 16, 2030
• Study Completion (Estimated): June 16, 2030
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); CA (2); NZ (1); PL (2); ES (3); IT (2)