NCT02895945: CHAWI

BAX 802 in CHA With Inhibitors

Terminated Phase 3 Results posted Last updated 20 October 2021

What this trial tests

Phase 3 trial testing Antihemophilic Factor (Recombinant), Porcine Sequence (BAX 802) in Hemophilia A in 8 participants. Terminated before completion.

Timeline

22 December 2016

Primary endpoint
22 January 2021

22 January 2021

Quick facts

Lead sponsor	Baxalta now part of Shire
Phase	Phase 3
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	8
Start date	22 December 2016
Primary completion	22 January 2021
Estimated completion	22 January 2021
Sites	24 locations across Italy, South Africa, Netherlands, Russia, Germany, Poland, Norway, Canada

Drugs / interventions tested

• Antihemophilic Factor (Recombinant), Porcine Sequence (BAX 802) — full drug profile →

Conditions studied

• Hemophilia A — all drugs for Hemophilia A →

Sponsor

Baxalta now part of Shire — full company profile →

Who can join

Adults 12 to 75, male only, with Hemophilia A. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Surgeries With a "Good" or "Excellent" Response as Measured by the Global Hemostatic Efficacy Assessment (GHEA) Score Primary · Day 1 up to discharge or Day 14 (whichever was earlier)

GHEA score consisted of 3 individual rating scales: (1) Intra-operative Efficacy Assessment Scale, (2) Post-operative Efficacy Assessment Scale, and (3) Overall Peri-operative Efficacy Assessment Scale. Scales 1 and 2 was performed by the operating surgeon on Day 1, and Scale 3 was performed by the investigator on Day 14. Each rating scale was based on 4 points scale ranging from: 3 (Excellent), 2 (Good), 1 (Fair), and 0 (None). Total score ranged from 0 to 9, where scores evaluated as: excellent (7 to 9), good (5 to 7), fair (3 to 4), and none (0 to 2). The scores of 3 individual ratings scal

GHEA rating: Good

Group	Value	95% CI
Major Surgeries	14.3

GHEA rating: Excellent

Group	Value	95% CI
Major Surgeries	71.4

Actual Blood Loss, Estimated Volume of Expected Average Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period Secondary · Intra-operative: up to completion of surgery (Day 1), Post-operative: at 24 hours post-surgery, and Peri-operative: at discharge or Day 14 (whichever was earlier)

Prior to the surgery, the surgeon/investigator predicted and compared the estimated volume (in milliliter \[mL\]) of the expected average blood loss and expected maximum blood loss for the planned surgical intervention in a comparable healthy individual with similar demographic characteristics; for intraoperative, postoperative, and overall perioperative time periods. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till 24 hours post-surgery. Peri-operative defined as period from

Intra-operative Period: Actual Blood Loss

Group	Value	95% CI
Major Surgeries	141.1	± 188.69

Intra-operative Period: Expected Average Blood Loss

Group	Value	95% CI
Major Surgeries	221.7	± 286.76

Intra-operative Period: Expected Maximum Blood Loss

Group	Value	95% CI
Major Surgeries	414.7	± 546.37

Post-operative Period: Actual Blood Loss

Group	Value	95% CI
Major Surgeries	31.0	± 66.56

Post-operative Period: Expected Average Blood Loss

Group	Value	95% CI
Major Surgeries	171.4	± 276.17

Post-operative Period: Expected Maximum Blood Loss

Group	Value	95% CI
Major Surgeries	378.0	± 570.94

Peri-operative Period: Actual Blood Loss

Group	Value	95% CI
Major Surgeries	164.1	± 215.15

Peri-operative Period: Expected Average Blood Loss

Group	Value	95% CI
Major Surgeries	465.0	± 744.85

Ratio of Actual Blood Loss and Estimated Volume of Expected Average Blood Loss During Intra-operative, Post-operative and Peri-operative Period Secondary · Intra-operative: up to completion of surgery (Day 1), Post-operative: at 24 hours post-surgery, and Peri-operative: at discharge or Day 14 (whichever was earlier)

Prior to the surgery, the surgeon/investigator predicted and compared the estimated volume (mL) of the expected average blood loss and expected maximum blood loss for the planned surgical intervention in a comparable healthy individual with similar demographic characteristics; for intraoperative, postoperative, and overall perioperative time periods. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till 24 hours post-surgery. Peri-operative defined as period from start of surgical

Intra-operative Period

Group	Value	95% CI
Major Surgeries	0.970	± 0.9486

Post-operative Period

Group	Value	95% CI
Major Surgeries	0.150	± 0.2236

Peri-operative Period

Group	Value	95% CI
Major Surgeries	0.545	± 0.3448

Ratio of Actual Blood Loss and Expected Maximum Blood Loss During Intra-operative, Post-operative and Peri-operative Period Secondary · Intra-operative: up to completion of surgery (Day 1), Post-operative: at 24 hours post-surgery, and Peri-operative: at discharge or Day 14 (whichever was earlier)

Prior to the surgery, the surgeon/investigator predicted and compared the estimated volume (mL) of the expected average blood loss and expected maximum blood loss for the planned surgical intervention in a comparable healthy individual with similar demographic characteristics; for intraoperative, postoperative, and overall perioperative time periods. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till 24 hours post-surgery. Peri-operative defined as period from start of surgical

Intra-operative Period

Group	Value	95% CI
Major Surgeries	0.555	± 0.6517

Post-operative Period

Group	Value	95% CI
Major Surgeries	0.058	± 0.0846

Peri-operative Period

Group	Value	95% CI
Major Surgeries	0.306	± 0.1962

Percentage of Major Surgeries With Good or Excellent Hemostatic Score Secondary · Day 1 up to discharge or Day 14 (whichever was earlier)

Percentage of major surgeries with good or excellent hemostatic score was analyzed by GHEA score. It consisted of 3 individual ratings: (1) Intra-operative Efficacy Assessment Scale, (2) Post-operative Efficacy Assessment Scale, (3) Postoperative Efficacy Assessment Scale. Ratings 1 and 2 was performed by the operating surgeon on Day 1, and Rating 3 was performed by the investigator on Day 14. Each rating scale was based on 4 point scale ranging from: 3 (Excellent), 2 (Good), 1 (Fair), and 0 (None). The scores of each of the 3 individual ratings scales, was added together to form a GHEA score.

Group	Value	95% CI
Major Surgeries	85.7	42.1 – 99.6

Average Daily Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period Secondary · Pre-operative: before surgery, Intra-operative: up to completion of surgery (Day 1), Post-operative: from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier)

Body-weight adjusted dose equals to amount infused/body-weight (kilogram \[kg\]), where amount infused as amount of drug infused (International Units \[IU\]) and body-weight as the last available body-weight (kg) prior to the infusion. Pre-operative defined as period prior to surgery. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Average daily weight-adjusted dose of BAX 802 per participant during each operative pe

Pre-operative

Group	Value	95% CI
Major Surgeries	162.471	± 125.7051
Minor Surgeries	208.779

Intra-operative

Group	Value	95% CI
Major Surgeries	76.083	± 35.1339

Post-operative

Group	Value	95% CI
Major Surgeries	43.549	± 56.0039

Total Weight-adjusted Dose of BAX 802 Per Participant During Pre-operative, Intra-operative and Post-operative Period Secondary · Pre-operative: before surgery, Intra-operative: up to completion of surgery (Day 1), Post-operative: from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier)

Body-weight adjusted dose equals to amount infused/body-weight (kg), where amount infused as amount of drug infused (IU) and body-weight as the last available body-weight (kg) prior to the infusion. Pre-operative defined as period prior to surgery. Intra-operative defined as period from start of surgery to completion of surgical procedure. Post-operative defined as period from completion of surgical procedure till discharge or 14 days post surgery (whichever was earlier). Total weight-adjusted dose of BAX 802 per participant during each operative period was reported.

Pre-operative

Group	Value	95% CI
Major Surgeries	162.471	± 125.7051
Minor Surgeries	208.779

Intra-operative

Group	Value	95% CI
Major Surgeries	76.083	± 35.1339

Post-operative

Group	Value	95% CI
Major Surgeries	625.520	± 399.4913

Volume of Blood Products Transfused Secondary · From initiation of the surgery up to discharge or Day 14 (whichever came earlier)

The volume (in mL) of blood products transfused from initiation of the intervention to discharge or Day 14 (whichever came earlier) was reported.

Group	Value	95% CI
Major Surgeries	950.0	± 70.71

Number of Participants With De Novo Inhibitors Secondary · Baseline up end of study (EOS) (up to 44 months)

De novo inhibitor was defined as a post-baseline inhibitor titer to FVIII (hFVIII or porcine factor VIII \[pFVIII\])of \>=0.6 Bethesda units per milliliter (BU/mL) given a baseline of \<0.6 BU/mL. Number of participants with de novo inhibitors were reported.

hFVIII

Group	Value	95% CI
Major Surgeries	0
Minor Surgeries	0

pFVIII

Group	Value	95% CI
Major Surgeries	3
Minor Surgeries	0

Number of Participants With Anamnestic Reactions Secondary · Baseline up to EOS (up to 44 months)

An anamnestic reaction was defined as an increase from a measurable baseline (\>0.6 BU/mL) in the inhibitor titer to FVIII (human or porcine) of \>=10 BU/mL. Number of participants with anamnestic reactions were reported.

hFVIII

Group	Value	95% CI
Major Surgeries	5
Minor Surgeries	0

pFVIII

Group	Value	95% CI
Major Surgeries	3
Minor Surgeries	0

Mean Change From Baseline up to EOS in Inhibitory and Binding Antibodies to pFVIII Secondary · Baseline up to EOS (up to 44 months)

The assessment of inhibitory antibodies (immunoglobulin G \[IgG\] and immunoglobulin M \[IgM\]) to pFVIII was determined using Bethesda assay, and assessment of binding antibodies (IgG and IgM) to pFVIII was determined using validated enzyme-linked immunosorbent assays (ELISAs). Mean change from baseline in inhibitory and binding antibodies to pFVIII was reported.

Group	Value	95% CI
Major Surgeries	111.15	± 149.072
Minor Surgeries	-0.20

Mean Change From Baseline up to EOS in Inhibitory and Binding Antibodies to hFVIII Secondary · Baseline up to EOS (up to 44 months)

The assessment of inhibitory antibodies (IgG and IgM) to hFVIII was determined using Bethesda assay, and assessment of binding antibodies (IgG and IgM) to hFVIII was determined using ELISA. Mean change from baseline in inhibitory and binding antibodies to hFVIII was reported.

Group	Value	95% CI
Major Surgeries	198.67	± 317.254
Minor Surgeries	-0.20

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to EOS (up to 44 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Major Surgeries

Serious: 6/7 (86%)

Deaths: 0/7

Minor Surgeries

Serious: 0/1 (0%)

Deaths: 0/1

Serious adverse events (5 terms)

Reaction	System	Major Surgeries	Minor Surgeries
Anti factor VIII antibody positive	Investigations	—	—
Anti factor VIII antibody increased	Investigations	—	—
Anamnestic reaction	Immune system disorders	—	—
Bacterial infection	Infections and infestations	—	—
Haemarthrosis	Musculoskeletal and connective tissue disorders	—	—

Other adverse events (9 terms — click to expand)

Reaction	System	Major Surgeries	Minor Surgeries
Anaemia	Blood and lymphatic system disorders	—	—
Tachycardia	Cardiac disorders	—	—
Pyrexia	General disorders	—	—
Oral herpes	Infections and infestations	—	—
Anaemia postoperative	Injury, poisoning and procedural complications	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Skin irritation	Skin and subcutaneous tissue disorders	—	—
Hypertension	Vascular disorders	—	—

Most-reported serious reactions: Anti factor VIII antibody positive, Anti factor VIII antibody increased, Anamnestic reaction, Bacterial infection, Haemarthrosis.

Data from ClinicalTrials.gov NCT02895945 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the efficacy and safety of BAX 802 in males with congenital hemophilia A (CHA) with inhibitors who are undergoing major or minor elective surgical, dental, or other invasive procedures.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Current and emerging factor VIII replacement products for hemophilia A.
   Cafuir LA, Kempton CL. · · 2017 · cited 38× · PMID 29051801 · DOI 10.1177/2040620717721458
2. Recombinant porcine factor VIII in patients with congenital haemophilia A with inhibitors undergoing surgery: Phase 3, single-arm, open-label study.
   Pfrepper C, Radossi P, Windyga J, Kavakli K, et al · · 2024 · PMID 38317504 · DOI 10.1111/hae.14932