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

Phase 1

Recruiting

Conditions: Severe or Moderate Hemophilia A with or without factor VIII inhibitors
MedDRA version: 20.0Level: LLTClassification code: 10060612Term: Hemophilia A Class: 10010331
Therapeutic area: Phenomena and Processes [G] - Chemical Phenomena [G02]
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
Therapeutic area: Diseases [C] - Hemic and Lymphatic Diseases [C15]

Registration Number: CTIS2023-503906-35-00

Lead Sponsor: F. Hoffmann-La Roche AG

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Male

Target Recruitment: 20

Inclusion Criteria

Body weight >= 40 kg at screening, Male (based on sex at birth), Diagnosis of severe (FVIII:C <1 IU/dL) or moderate [FVIII coagulant activity (FVIII:C) between >= 1 IU/dL and <= 5 IU/dL)] congenital hemophilia A (HA) 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 (IVR) > 66%

Exclusion Criteria

Inherited or acquired bleeding disorders other than congenital HA, Protein C activity, protein S free antigen, or anti-thrombin III activity levels below the lower limit of the reference range at screening, At high risk for thrombotic microangiopathy (TMA), including past personal or family history of TMA, in the investigator’s judgment, 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, Personal history of ischemic heart disease, cerebrovascular disease, or diabetes mellitus, History of severe allergic or anaphylactic reactions to monoclonal antibody therapy and to chimeric or humanized antibodies or fusion proteins

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety of multiple doses of NXT007;Secondary Objective: To characterize the pharmacokinetics of NXT007 following multiple doses of NXT007, To evaluate the immunogenicity of multiple doses of NXT007, To evaluate the recurrence of or de novo factor VIII (FVIII) inhibitor occurrence, and change to FVIII inhibitor titer over time, To explore the efficacy of multiple doses of NXT007;Primary end point(s): 1. Incidence and severity of adverse events with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0), 2. Change from baseline in selected clinical laboratory test results, 3. Change from baseline in vital signs and electrocardiogram (ECG) parameters

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):1. Plasma concentration of NXT007 at specified timepoints and relevant pharmacokinetic (PK) parameters;Secondary end point(s):2. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study;Secondary end point(s):3. Number and proportion of participants with anti-FVIII inhibitors (titer >= 0.6 BU/mL) at specified timepoints;Secondary end point(s):4. Number of bleeding events over time;Secondary end point(s):5. Annualized bleeding rate (ABR) for treated bleeds, all bleeds, treated spontaneous bleeds, and treated joint bleeds

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