Post-Authorization Safety, Tolerability and Immunogenicity Evaluation of HyQvia in Pediatric PIDD Subjects

Baxalta

Status and phase: Completed; Phase 4

Conditions: Primary Immunodeficiency Diseases (PID)

Treatments: Biological: Cuvitru; Biological: KIOVIG; Biological: HYQVIA

Study type: Interventional

Funder types: Industry

Identifiers

NCT03116347

161504

2016-003438-26 (EudraCT Number)

Details and patient eligibility

About

The purpose of the study is to acquire additional data on safety, tolerability and immunogenicity of HyQvia in pediatric (age two to <18 years) patients with Primary Immunodeficiency Diseases (PIDD)

Enrollment: 42 patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Participant must have a documented diagnosis of a form of primary humoral immunodeficiency involving a defect in antibody formation and requiring gammaglobulin replacement, as defined according to the International Union of Immunological Societies (IUIS) Scientific Committee 2015 prior to enrollment. The diagnosis must be confirmed by the sponsor´s Medical Director prior to first treatment with investigational product (IP) in the study.
2. Participant is at least two and below 18 years of age at the time of screening.
3. Participant has been receiving a consistent dose of Immunoglobulin G (IgG), administered in compliance with the respective product information for a period of at least three months prior to screening. The average minimum pre-study dose over that interval was equivalent to 300 mg/kg body weight (BW)/four weeks and a maximum dose equivalent to 1000 mg/kg BW/4 weeks.
4. Participant has a serum trough level of IgG > 5 g/L at screening.
5. If female of childbearing potential, participant presents with a negative pregnancy test and agrees to employ adequate birth control measures for the duration of the study.
6. Participant /legally authorized representative is willing and able to comply with the requirements of the protocol.

Exclusion criteria

1. Participant has a known history of or is positive at screening for one or more of the following: hepatitis B surface antigen (HBsAg), polymerase chain reaction (PCR) for hepatitis C virus (HCV), PCR for human immunodeficiency virus (HIV) Type 1/2.

2. Abnormal laboratory values at screening meeting any one of the following criteria (abnormal tests may be repeated once to determine if they are persistent):

   1. Persistent alanine aminotransferase (ALT) and aspartate amino transferase (AST) >2.5 times the upper limit of normal (ULN) for the testing laboratory
   2. Persistent severe neutropenia (defined as an absolute neutrophil count [ANC] ≤ 500/mm^3)

3. Participant has anemia that would preclude phlebotomy for laboratory studies, according to standard practice at the site.

4. Participant has an ongoing history of hypersensitivity or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following intravenous (IV) immunoglobulin, subcutaneous (SC) immunoglobulin, and/or Immune Serum Globulin (ISG) infusions.

5. Participant has severe immunoglobulin A (IgA) deficiency (< 7.0 mg/dL) with known anti-IgA antibodies and a history of hypersensitivity. .

6. Participant has a known allergy to hyaluronidase.

7. Participant has active infection and is receiving antibiotic therapy for the treatment of infection at the time of screening.

8. Participant has a bleeding disorder or a platelet count < 20,000/μL, or who, in the opinion of the investigator, would be at significant risk of increased bleeding or bruising as a result of SC therapy.

9. Participant has severe dermatitis that would preclude adequate sites for safe product administration in the opinion of the investigator.

10. Participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study.

11. Participant is a family member or employee of the investigator.

12. If female, participant is pregnant or lactating at the time of enrollment.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

42 participants in 3 patient groups

EPOCH 1

Experimental group

Description:

Ramp up period for participants who were not treated with HyQvia prior to this study

Treatment:

Biological: HYQVIA

EPOCH 2

Experimental group

Description:

Participants who were treated with HyQvia prior to this study, and those who completed the ramp up period (Epoch 1). After one year in Epoch 2, participants with anti-rHuPH20 antibody titer \<160 at all time-points during the study will complete the study termination/completion visit at the next possible occasion. Participants with anti-rHuPH20 antibody titer \>=160 during the study and/or at the last measurement will continue for an additional two years of HyQvia treatment and observation.

Treatment:

Biological: HYQVIA

Epoch 3

Experimental group

Description:

Safety follow-up for participants whose anti-rHuPH20 antibody titer was \>= 160 during Epoch 1 or Epoch 2 and who experience either a related serious adverse event (SAE) or a related severe adverse event (AE)

Treatment:

Biological: KIOVIG

Biological: Cuvitru