Protocol Title: Phase 3, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of PF-07055480 (Recombinant AAV2/6 Human Factor VIII Gene Therapy) in Adult Male Participants with Moderately Severe to Severe Hemophilia A (FVIII:C≤1%)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pfizer Inc.

Participant type

Patients

Age range

18-64 years

Gender

Male

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

14 Jun 2021 → ongoing

Decision date (initial)

2024-07-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Pfizer Inc.

External identifiers

EU CT number

2024-512075-12-00

EudraCT number

2019-004451-37

ClinicalTrials.gov

NCT04370054

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Efficacy, Safety, Pharmacodynamic, Pharmacogenetic, Therapy

Evaluate the efficacy of a single infusion of PF-07055480 in participants≥18 and <65 years of age with moderately severe to severe hemophilia A (FVIII C ≤ 1%).

Secondary objectives 4

1. To demonstrate that the use of exogenous FVIII is significantly reduced post PF-07055480 infusion.
2. To assess additional efficacy parameters post PF-07055480 infusion including FVIII activity level, use of exogenous FVIII, information on bleeding events and PROs.
3. Estimate the durability of efficacy up to 5 years after PF-07055480 infusion.
4. To estimate the safety and tolerability of PF-07055480, including immunogenicity, for the study duration of 5 years after PF-07055480 infusion.

Conditions and MedDRA coding

hemophilia A

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. Males who have been followed on routine Factor VIII prophylaxis therapy in the lead-in study (C0371004) and have ≥ 150 documented exposure days to a Factor VIII protein product
2. Moderately severe to severe hemophilia A (Factor VIII activity ≤ 1%)
3. Suspension of FVIII prophylaxis therapy post study drug infusion

Exclusion criteria 7

1. Anti-AAV6 neutralizing antibodies
2. History of inhibitor to Factor VIII
3. Laboratory values at screening visit that are abnormal or outside acceptable study limits
4. Significant and/or unstable liver disease, biliary disease, significant liver fibrosis
5. Planned surgical procedure requiring Factor VIII surgical prophylactic factor treatment 12 months from screening visit
6. Active hepatitis B or C
7. Serological evidence of human immunodeficiency virus HIV-1 or HIV-2 with either Cluster of Differentiation 4 positive (CD4+) cell count ≤200 mm3 or viral load >20 copies/mL

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Total annualized bleeding rate (ABR, spontaneous and traumatic bleedings, treated and untreated) from Week 12 through at least 15 months following PF-07055480 infusion versus Total ABR on prior Factor VIII (FVIII) prophylaxis replacement regimen.

Secondary endpoints 10

1. Factor VIII (FVIII) activity level >5% at 15 months following infusion of PF-07055480.
2. ABR (spontaneous and traumatic treated bleedings) from Week 12 through at least 15 months following PF-07055480 infusion versus ABR on prior FVIII prophylaxis replacement regimen.
3. Annualized infusion rate (AIR) of exogenous FVIII from Week 12 through at least 15 months following infusion of PF-07055480 versus AIR on prior FVIII prophylaxis replacement regimen.
4. FVIII activity level from Week 12 through 15 months following infusion of PF-07055480.
5. The following secondary parameters will be assessed from Week 12 through at least 15 months after PF-07055480 infusion and compared with prior FVIII prophylaxis replacement regimen: • Annualized FVIII consumption. • Annualized bleeding rate (ABR) of specific type: o by cause (spontaneous or traumatic) o by location (in joints, in target joints, or in soft tissue). • Total ABR by cause and by location. • Percentage of participants without bleeds.
6. The following secondary parameters will be assessed by visit after PF- 07055480 infusion: • FVIII activity level. • Change from baseline in joint health as measured by the HJHS instrument. • Change from baseline in the following patient-reported outcome (PRO) endpoints: o Haemophilia Quality of Life Questionnaire for Adults (Haem-AQoL) o Haemophilia Activities List (HAL).
7. The following parameters will be analysed yearly or by visit as appropriate: • ABR. • FVIII activity level. • AIR of exogenous FVIII. • Annualized FVIII consumption. • ABR of specific type: o by cause (spontaneous or traumatic). o by location (in joint, in target joints, or in soft tissue). • Total ABR. • Total ABR by cause and by location. • Percentage of participants without bleeds.
8. The following parameters will be analysed yearly or by visit as appropriate: • Change from baseline in joint health as measured by the HJHS instrument. • Change from baseline in PRO endpoints: Haem-A-QoL and HAL. In addition, ABR, Total ABR, and AIR will be analyzed throughout the 5 year study period.
9. - Incidence and severity of adverse events (AEs). - Events of special interest (such as hypersensitivity reactions, clinically reported thrombotic events, and malignancy).
10. - Immunogenicity: • Antibodies against adeno-associated virus 6 (AAV6) capsid protein (neutralizing antibodies [nAbs] and anti-drug antibodies [ADAs]). • T-cell responses against AAV6 capsid and against the transgene. • FVIII inhibitors.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pfizer Inc.

Sponsor organisation

Pfizer Inc.

Address

66 Hudson Boulevard East

City

New York

Postcode

10001-2189

Country

United States

Scientific contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Public contact point

Organisation

Pfizer Inc.

Contact name

Clinical Medical Lead

Third parties 6

Locations

5 EU/EEA countries · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 38 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications