An Open Label, Multicenter Study to Evaluate the Pharmacokinetics, Efficacy and Safety of ASCENIV™ (IGIV) in Pediatric Subjects With Primary Immunodeficiency Diseases (PIDD)

This is a Phase IV, multicenter, open-label study of Asceniv™ administered as an intravenous infusion of Asceniv™ (IGIV) 300-800 mg/kg every 21 or 28 days in approximately 12 pediatric subjects with Primary Immunodeficiency Diseases (PIDD). The study will be conducted at 5-7 centers in the United States, with subjects receiving six (28 day cycle) or seven (21 day cycle) doses of Asceniv™ during the study.

Study Overview

• Status: Recruiting
• Conditions: Primary Immune Deficiency
• Intervention / Treatment: Biological: Asceniv™

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Rebecca Avila; Phone Number: 561-989-5853; Email: reavila@admabio.com
• Study Contact Backup: Name: Amy Doman; Email: adoman@admabio.com

Study Locations

• United States
  • Colorado
    • Centennial, Colorado, United States, 80112
      • Not yet recruiting
      • IMMUNOe Research Centers
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Not yet recruiting
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 11 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject and/or legal guardian must be able to understand the study procedures, have agreed to participate in the study and have voluntarily signed an IEC/IRB approved written informed consent. The consent form or a specific assent form, where required, will be signed and dated by minors.
2. Have confirmed and documented clinical diagnosis of primary immunodeficiency disease including but not limited to: common variable immunodeficiency, X-linked and autosomal forms of agammaglobulinemia, hyper-IgM syndrome, or antibody deficiencies.
3. Be male or female, and ≥ 2 years and < 12 years at the time of informed consent by subject or legal guardian.
4. Have been receiving IGIV at a dose that has not been changed by > 25% of the mean dose on a mg/kg basis for at least 3 months prior to study entry.
5. Have two trough levels of IgG in the last year (screening level may be used), and maintained a trough serum IgG level > 500 mg/dL on the previous 2 assessments prior to receiving Asceniv™. (The trough level must be at least 300 mg/dL above pre-treatment serum IgG levels; with exception for cases of X-linked agammaglobulinemia where no pre-treatment value is available. Documentation will need to include dose, treatment interval and trade name of the IGIV products used for the three doses prior to the first Asceniv™ infusion in this study.
6. For female subjects, be of non-childbearing potential or have a negative pregnancy test prior to study start and be deemed not at risk of becoming pregnant by adherence to a reliable contraceptive method for the duration of the study. Females of non-childbearing potential are defined as prepubertal girls.

Exclusion Criteria:

1. Have a known hypersensitivity to immunoglobulin or any excipient in Asceniv™.
2. Have a history of any severe anaphylactic or anaphylactoid reaction to blood or any blood-derived product.
3. Have a specific Immunoglobulin A (IgA) deficiency (IgA ≤ 5 mg/dL and normal IgG and IgM), history of allergic reaction to products containing IgA or has demonstrable antibodies to IgA.
4. Have uncompensated, hemodynamically significant, congenital or other heart disease. Including but not limited to acute coronary syndromes and chronic stable angina.
5. Have a medical condition that is known to cause secondary immune deficiency, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, or HIV infection.
6. Have a significant T-cell or granulocyte deficiency in number or function (chronic or recurrent absolute neutrophil count <1000 x 109/L).
7. Have significant renal impairment (defined as an estimated Glomerular Filtration Rate ≤ 50 mL/min/1.73m2); or have a history of acute renal failure.
8. Have abnormal liver function, defined as ALT or AST ≥ 2.5 x ULN.
9. Have any chronic lung disease (uncontrolled or chronic, severe asthma, etc.)
10. Have an infusion port, catheter, or other foreign body present (excluding PE tubes). Long-standing, infection-free ports may be permitted at the discretion of the Medical Monitor.
11. Be planned or scheduled to undergo surgery during the course of study participation.
12. Have ongoing failure to thrive per PI assessment.
13. Be receiving chronic anti-coagulation therapy.
14. Have a history of DVT, thrombotic or thrombo-embolic event, or are at increased risk for thrombotic event due to presence of, but not limited to, atrial fibrillation, disease or injury requiring prolonged immobilization, or other risk factor(s) including significant proteinuria or protein losing enteropathy.

15. Current daily use of the following medications:

    • corticosteroids (> 0.15 mg/kg/day of prednisone equivalent) Note: Intermittent corticosteroid use during the study is allowable, if medically necessary and approved by the ADMA Medical Director: i.e. 1 mg/kg twice a day for ten days to a maximum of 40 mg per dose
    • immunomodulatory drugs (e.g. TNF (inhibitors -Enbrel, Humira, etc.) Xolair and Dupixent administration permitted.
    • immunosuppressive drugs (excluding topical pimecrolimus (Elidel) and tacrolimus (Protopic))
16. Administration of a hyperimmune or specialty high titer Immunoglobulin product (e.g. Cytogam, VZIG, HBIG, etc.) within 30 days of screening, or expectation that a hyperimmune Immunoglobulin product will be given during the course of the study.
17. Have uncontrollable arterial hypertension.
18. Have anemia at screening (hemoglobin <10 g/dL).
19. Have a history of hemolysis while undergoing treatment with IGIV therapy.
20. Be morbidly obese as indicated by a Body Mass Index (BMI) ≥40.
21. Have an active viral or bacterial infection or symptoms/signs consistent with such an infection, within the two weeks prior to the Screening Visit. Subjects may be receiving antibiotics as long as signs/symptoms of infection have been absent for two weeks prior to the initial infusion of investigational product (IP).
22. Have received any blood product (other than Immunoglobulin G) within 3 months prior to screening.
23. Have received any RSV specific products, including palivizumab (Synagis®) within 3 months prior to screening.
24. Have abused alcohol, opiates, psychotropic agents, or other chemicals or drugs within the past 12 months.
25. Have an acute or chronic medical condition that, in the opinion of the investigator, may interfere with the conduct of the study.
26. Have any condition judged by the study physician to preclude participation in the study, including any psychological disorder, which might hinder compliance.
27. Have any laboratory assessment result that, in the opinion of the investigator, warrants exclusion from participation in the study.
28. Are currently pregnant or nursing.
29. Have acute hepatitis A, acute or chronic Hepatitis B or C, or HIV infection.
30. Have received investigational product within 3 weeks of the anticipated first infusion of Asceniv™.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Asceniv; Asceniv™ will be given as an intravenous infusion at the same dose, or higher dose where medically appropriate, as the subject's previous IV Immunoglobulin G treatment (300-800 mg/kg) every 21 or 28 days.

Biological: Asceniv™; Each subject will receive an intravenous infusion of Asceniv™ on Study Day 1 (required to be within 28 days of screening) and every 21 or 28 days thereafter according to their current interval of IGIV treatment. Subjects will receive Asceniv™ at the same dose or higher dose if medically appropriate (300-800 mg/kg), every 21 or 28 days for five months (seven or six doses respectively).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax	Pharmacokinetic measure at 6th or 7th infusion	At prior to, end of infusion, and 60 minutes, 2 hours, 24 hours, 48 hours, 4 days, 7 days, 14 days, and either 21 or 28 days dependent upon infusion schedule
Tmax	Pharmacokinetic measure at 6th or 7th infusion	At prior to, end of infusion, and 60 minutes, 2 hours, 24 hours, 48 hours, 4 days, 7 days, 14 days, and either 21 or 28 days dependent upon infusion schedule
AUC(0-ʈ)	Pharmacokinetic measure at 6th or 7th infusion	At prior to, end of infusion, and 60 minutes, 2 hours, 24 hours, 48 hours, 4 days, 7 days, 14 days, and either 21 or 28 days dependent upon infusion schedule
AUC(0-∞)	Pharmacokinetic measure at 6th or 7th infusion	At prior to, end of infusion, and 60 minutes, 2 hours, 24 hours, 48 hours, 4 days, 7 days, 14 days, and either 21 or 28 days dependent upon infusion schedule
Terminal phase elimination half-life (ʈ½)	Pharmacokinetic measure at 6th or 7th infusion	At prior to, end of infusion, and 60 minutes, 2 hours, 24 hours, 48 hours, 4 days, 7 days, 14 days, and either 21 or 28 days dependent upon infusion schedule
Terminal phase elimination rate (λZ)	Pharmacokinetic measure at 6th or 7th infusion	At prior to, end of infusion, and 60 minutes, 2 hours, 24 hours, 48 hours, 4 days, 7 days, 14 days, and either 21 or 28 days dependent upon infusion schedule

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infections	Number of infections of any kind, serious and non-serious	Up to approximately 7 months
Serious Bacterial Infections	Incidence of Serious Bacterial Infections	Up to approximately 7 months
Other Infections	Incidence of infections other than Serious Bacterial Infections	Up to approximately 7 months
Hospitalizations	Number of hospitalizations due to infections	Up to approximately 7 months
Total IgG Trough	Levels taken before each infusion	At each visit through study completion, up to approximately 7 months
IgG Subclasses	Levels of subclasses 1-4 before infusion	Prior to first and last infusions
Antibodies	Levels of specific antibodies (anti-pneumococcal capsular polysaccharide, anti-haemophilus influenzae b, and anti-RSV neutralizing antibody)	Prior to first and last infusions

Collaborators and Investigators

• Sponsor: ADMA Biologics, Inc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2022
• Primary Completion (ANTICIPATED): March 31, 2023
• Study Completion (ANTICIPATED): June 30, 2023

Study Registration Dates

• First Submitted: September 23, 2021
• First Submitted That Met QC Criteria: October 4, 2021
• First Posted (ACTUAL): October 7, 2021

Study Record Updates

• Last Update Posted (ACTUAL): September 16, 2022
• Last Update Submitted That Met QC Criteria: September 13, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Genetic Diseases, Inborn; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases
• Other Study ID Numbers: ADMA-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No