SPK-8011QQ gene therapy for adults with severe or moderately severe hemophilia A

A Phase 2b, Single-Arm, Open-Label, Multicenter Study of the Safety of SPK-8011QQ in Adults With Severe or Moderately Severe Hemophilia A

This trial will test a one-time gene therapy called SPK-8011QQ in adult men with severe or moderately severe hemophilia A to see if it is safe and well tolerated.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 5 (estimated)
• Ages: 18 Years and up
• Sex: Male
• Sponsor: Hoffmann-La Roche (Industry-sponsored)
• Locations: 2 sites (Orange, California and 1 other locations)
• Trial ID: NCT07226206 on ClinicalTrials.gov

What this trial studies

This Phase 1/2 interventional trial gives adult males with severe or moderately severe hemophilia A a dose of SPK-8011QQ and monitors safety and tolerability over time. Participants must have endogenous FVIII activity ≤3% and a documented history of FVIII treatment or frequent bleeds, and they provide informed consent. Study staff will collect laboratory measures including FVIII activity, record adverse events, and track bleeding and factor use during follow-up visits. The trial is conducted at two California sites and is sponsored by Hoffmann‑La Roche.

Who should consider this trial

Good fit: Adult males (assigned male at birth) aged 18 or older with severe or moderately severe hemophilia A (FVIII ≤3%) who have been on FVIII prophylaxis for at least six months or had ≥5 bleeds in the prior six months and can give informed consent.

Not a fit: People with mild hemophilia A, FVIII levels above 3%, females, or those who do not meet the documented treatment or bleeding-history requirements—or who have excluded medical conditions or prior hypersensitivity—are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, the therapy could raise factor VIII levels and reduce the need for regular FVIII infusions and bleeding episodes.

How similar studies have performed: Other AAV-based FVIII gene therapy programs have produced meaningful increases in FVIII activity in some patients but have shown variable durability and immune-related challenges, so results are promising but not yet definitive.

Eligibility criteria

Inclusion Criteria:

* Signed Informed Consent Form (ICF)
* ≥18 years of age at the time of signing the ICF
* Male sex assigned at birth
* Severe or moderately severe hemophilia A, defined as endogenous FVIII:C activity levels ≤3%, as documented (historically or during the Screening Period) by a certified laboratory and where the FVIII:C level is measured more than 96 hours after the prior dose of an extended half-life FVIII replacement product or more than 72 hours after the prior dose of a standard half-life FVIII replacement product
* Have documented treatment for a minimum of 6 months prior to screening with either of the following: plasma coagulation factor VIII (FVIII) prophylaxis, defined as receiving a prescribed dose and frequency of FVIII infusions with the intent to treat continuously for 52 weeks per year; or FVIII on demand, with a history of ≥ 5 breakthrough bleeds in the 6 months prior to screening
* No prior history of hypersensitivity or anaphylaxis associated with the administration of any FVIII product
* Have ≥150 exposure days to a FVIII protein product such as recombinant, plasma-derived, or extended half-life FVIII product
* Negative screening test for inhibitor against FVIII (i.e., \<0.6 BU)
* Candidates with prior FVIII inhibitors who are tolerized having completed successful ITI at least 5 years before screening are eligible provided they have had no evidence of inhibitor recurrence (permanent or temporary) within 5 years prior to screening as may be indicated by detection of an inhibitor, FVIII half-life \<6 hours, or FVIII recovery \<66% since completing ITI
* Confirmed negative anti-Spark200 antibodies as documented through central laboratory testing of a serum sample
* Acceptable hepatobiliary function according to all of the following criteria: ALT, AST, and ALP ≤2×ULN and INR \<1.4 at the time of screening; No evidence of cirrhosis or advanced liver disease on screening liver ultrasound; Otherwise no laboratory or clinical evidence of liver disease or cirrhosis, per the Investigator's judgement
* Adequate renal function, defined as creatinine clearance ≥30 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration formula; patients on dialysis are not eligible for the study
* Platelet count ≥50,0000 cells/µL
* Negative HIV test at screening, with the following exception: Individuals with a positive HIV test at screening are eligible provided they are stable on an antiretroviral treatment regimen, have a cluster of differentiation (CD4) count \>200/mm3, and undetectable viral load (\<50 gc/mL)
* Negative hepatitis B surface antigen (HBsAg) at screening
* Positive hepatitis surface antibody (HBsAb) at screening, or a negative HBsAb at screening accompanied by either of the following: Negative hepatitis B core antibody (HBcAb); Positive HBcAb and negative hepatitis B virus (HBV) DNA test
* Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test at screening accompanied by negative HCV RNA test
* Otherwise appropriate medical history and physical and laboratory evaluation that are acceptable for inclusion in this clinical trial
* Are able and willing to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the completion of applicable patient-reported outcome questionnaires
* Agreement to adhere to the contraception requirements described in the protocol

Exclusion Criteria:

* Are currently undergoing antiviral therapy for chronic hepatitis B or chronic hepatitis C
* Have an inherited or acquired bleeding disorder other than hemophilia A
* Have known inherited or acquired thrombophilia, have signs of thromboembolic disease in the Investigator's judgement, or are on current treatment for thromboembolic disease. A history of previous catheter-associated thrombosis for which anti-thrombotic treatment is not currently ongoing is not considered an exclusion criterion
* Have had prior treatment with a vector or gene transfer agent. Nucleic acid-based vaccines, such as the vaccine for coronavirus disease 2019 (COVID-19), are not considered gene transfer agents
* Are receiving an investigational drug concurrently or have received an investigational drug within 30 days or 5 half-lives of the last investigational drug administration, whichever is longer
* Have a major surgical procedure planned in the 15-month period following SPK-8011QQ infusion
* Are unable (or unwilling) to receive blood or blood products (or any standard-of-care treatment for a life-threatening condition)
* Have concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study or that would, in the opinion of the Investigator preclude the candidate's safe participation in and completion of the study, or the interpretation of the study results
* History of malignancy within 5 years prior to screening and up to investigational study drug administration (Day 1) with the following exceptions: Participants with curatively treated basal or squamous cell carcinoma of the skin at any time prior to investigational study drug administration (Day 1) are eligible

Where this trial is running

Orange, California and 1 other locations

• Center for Inherited Blood Disorders — Orange, California, United States (Recruiting)
• Kaiser Permanente — Vallejo, California, United States (Recruiting)

Study contacts

• Study coordinator: Reference Study ID Number: XO46084 https://forpatients.roche.com/

Conditions Hemophilia A