Study type

Study type

Non-interventional study

Scope of the study

Safety study (incl. comparative)

Data collection methods

Secondary use of data
Non-interventional study

Non-interventional study design

Cohort
Study drug and medical condition

Name of medicine

HEMLIBRA

Study drug International non-proprietary name (INN) or common name

EMICIZUMAB

Anatomical Therapeutic Chemical (ATC) code

(B02BX06) emicizumab
emicizumab

Medical condition to be studied

Haemophilia A without inhibitors
Population studied

Short description of the study population

Patients of all ages with moderate congenital Haemophilia A, without FVIII inhibitors and with severe bleeding phenotype, treated with emicizumab

Age groups

All
Paediatric Population (< 18 years)
Preterm newborn infants (0 – 27 days)
Term newborn infants (0 – 27 days)
Children (2 to < 12 years)
Adolescents (12 to < 18 years)
Adult and elderly population (≥18 years)
Adults (18 to < 65 years)
Adults (18 to < 46 years)
Adults (46 to < 65 years)
Elderly (≥ 65 years)
Adults (65 to < 75 years)
Adults (75 to < 85 years)
Adults (85 years and over)

Estimated number of subjects

200
Study design details

Study design

This non-interventional (NI) PASS is a multi-country, registry-based, longitudinal cohort study based on secondary use of data collected for patients of all ages with moderate congenital Haemophilia A, without FVIII inhibitors and with severe bleeding phenotype, treated with emicizumab.

Main study objective

The aim of the study is to evaluate the long-term safety profile of emicizumab in patients with moderate congenital Haemophilia A (FVIII 1%-5%) without FVIII inhibitors and with severe bleeding phenotype and who are exposed to emicizumab in real-world settings, with a specific focus on thromboembolic (TE) events. The primary objective for this study is to determine the incidence of TE events.

Setting

Inclusion criteria:
• Diagnosis of congenital Haemophilia A (HA);
• Moderate disease classification (FVIII 1%-5%);
• Severe bleeding phenotype;

The above-mentioned inclusion criteria will ensure that the patient is eligible for the extended indication of emicizumab.

In addition, the patient will have to fulfil the following criteria:
• Initiation of emicizumab treatment during the cohort entry period;
• Information on previous HA outcomes and HA treatments approximately 12 months prior to the index date. In case HA diagnosis occurred within 12 months of the index date, the required lookback period will be shortened to time from HA diagnosis to index date. Anamnestic information capturing historic events but entered in the registry database less than 12 months before the index date will be considered as long as they were recorded prior to the index date;
• Information on risk factors of thromboembolic (TE) events (e.g., medical comorbidities, treatments and demographic characteristics) approximately 12 months prior to the index date. If the patient is below 1 year of age, the lookback period will be shortened to birth until index date. Anamnestic information capturing historic events but entered in the registry database less than 12 months before the index date will be considered as long as they were recorded prior to the index date;
• Signed the informed consent form where required by local regulations.

Exclusion criteria:
• Development of FVIII inhibitors any time before the index date;
• Treatment with emicizumab at any time before the index date.

Outcomes

The primary objective for this study is to determine the incidence of TE events.
The secondary objectives for this study are:
1. To determine the incidence of serious adverse events (SAEs).
2. To determine the incidence of thrombotic microangiopathy (TMA) events.
3. To determine the incidence of serious systemic hypersensitivity reactions, including anaphylaxis.
4. To characterise the risk profile in terms of pre-defined risk factors of TE events in the patient population.
5. To describe characteristics of TE events, SAEs, TMA events, and serious systemic hypersensitivity reactions, including anaphylaxis (e.g., diagnosis and symptoms).
6. To characterise the impact of the prior use of FVIII prophylaxis on the incidence of TE events, SAEs, TMA events, and serious systemic hypersensitivity reactions, including anaphylaxis.

Data analysis plan

For the primary objective, crude incidence rates (IRs) for 1st TE events during the follow-up period per 100 person-years (PY) will be described. For the calculation of crude IRs, the denominator will be the pooled person-time of all the patients within the cohort and the numerator will be all first events occurring during the follow-up period. In addition of crude IRs, incidence proportions will also be calculated.

For the analysis of secondary objectives 1, 2, 3, 4 and 6, crude IRs per 100 PY will be calculated, and for secondary objective 5, descriptive tabulations will be done for SAE and TE events.

For secondary objective 1, 2, 3 the numerators will be the number of first occurrences of any SAE, 1st TMA events and 1st serious systemic hypersensitivity reaction events during the follow-up period, respectively. The denominators for the crude IRs will be the pooled person-time. For secondary objective 4, the events will be counted for each category/stratum of relevant pre-defined risk factors of TE events, to yield crude IRs of TE per category/stratum. For analysis of secondary objective 5, characteristics of TE events, SAEs, TMA events, and serious systemic hypersensitivity reactions, including anaphylaxis (e.g., diagnosis and symptoms), will be tabulated. In addition, time to the 1st TE events, SAE, TMA events, and serious systemic hypersensitivity reactions, including anaphylaxis events will be described by Kaplan-Meier curves. For analysis of secondary objective 6, calculation of crude IR and crude incidence proportion of TE events, SAEs, TMA events, and serious systemic hypersensitivity reactions, including anaphylaxis, will be calculated, and tabulated for FVIII prophylaxis use (yes/no) prior to emicizumab treatment.