Primary ImmunodeficiencyPhase 3NCT02604810

Safety and Pharmacokinetics of IGSC 20% in Subjects With Primary Immunodeficiency

A Phase 3 study testing IGIV-C 10% and IGSC 20% in people with Primary Immunodeficiency, run by Grifols Therapeutics LLC at 25 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 2 to 75 years
Conditions the study is for: Primary Immunodeficiency
What is being tested?: IGIV-C 10% and IGSC 20%
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 53 participants
Where: 25 sitesin 2 countries
Study dates: Jan 2016to Dec 2017
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 to 75 years
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

Pre-existing diagnosis of primary immunodeficiency with features of hypogammaglobulinemia requiring IgG replacement therapy
No serious bacterial infection within the last 3 months prior to or during Screening
Currently on IgG replacement therapy (via IV or SC infusion) for ≥3 consecutive months. Subjects receiving IGIV must be receiving a dosage of 300 to 800 mg/kg per infusion
Documented (at least once within previous 3 months) IgG trough level of ≥500 mg/dL on current IgG replacement therapy regimen

Who cannot join

Known serious adverse reaction to immunoglobulin or any severe anaphylactic reaction to blood or any blood-derived product
History of blistering skin disease, clinically significant thrombocytopenia, bleeding disorder, diffuse rash, recurrent skin infections, or other disorders where SC therapy would be contraindicated during the study
Isolated IgG subclass deficiency, isolated specific antibody deficiency disorder, or transient hypogammaglobulinemia of infancy
Nephrotic syndrome, and/or a history of acute renal failure and/or severe renal impairment, and/or on dialysis
History (year prior to Screening or 2 episodes in lifetime ) of or current diagnosis of deep venous thrombosis or thromboembolism (eg, deep vein thrombosis, myocardial infarction, cerebrovascular accident or transient ischemic attack)
Acquired medical condition known to cause secondary immune deficiency, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (absolute neutrophil count less than 1000/μL [1.0 x 10^9/L]), or human immunodeficiency virus infection/acquired immune deficiency syndrome

Show all 9Show fewer

Known previous infection with or clinical signs and symptoms consistent with current hepatitis B virus or hepatitis C virus infection
Non-controlled arterial hypertension (systolic blood pressure >160 mmHg and/or diastolic blood pressure >100 mmHg in adult subjects)
Receiving any of the following medications: (a) immunosuppressants including chemotherapeutic agents, (b) immunomodulators, (c) long-term systemic corticosteroids defined as daily dose >1 mg of prednisone equivalent/kg/day for>30 days Note: Intermittent courses of corticosteroids of not more than 10 days would not exclude a subject. Inhaled or topical corticosteroids are allowed.

Trial locations and contacts

25 sites in 2 countries.

Country

City, postcode or hospital

25 sites in 2 countries

United States20 sites

Emory Children's Center
Atlanta, Georgia, 30322
Rush University Medical Center
Chicago, Illinois, 60612
AARA Research Center
Dallas, Texas, 75231
National Jewish Health
Denver, Colorado, 80206
Children's Hospital of Michigan - Wayne State University
Detroit, Michigan, 48201
Duke University Medical Center
Durham, North Carolina, 27710
Penn State University
Hershey, Pennsylvania, 17033
Baylor Texas Children's Hospital
Houston, Texas, 77030
UCLA Medical Center
Los Angeles, California, 90095
University of Miami - Batchelor Children's Research Institute
Miami, Florida, 33136
Allergy Associates of The Palm Beaches, PA
North Palm Beach, Florida, 33408
Oklahoma Institute of Allergy and Asthma Clinical Research
Oklahoma City, Oklahoma, 73131
Midwest Immunology
Plymouth, Minnesota, 55446
Children's Hospital of Richmond at VCU, VCU Medical Center
Richmond, Virginia, 23298
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
AIRE Medical of Los Angeles
Santa Monica, California, 90404
The South Bend Clinic
South Bend, Indiana, 46617
Washington University Medical Center
St Louis, Missouri, 63110
University of South Florida
St. Petersburg, Florida, 33701
Vital Prospects Clinical Research Institute, PC
Tulsa, Oklahoma, 74136

Other trials in United States

Canada5 sites

CHU Sainte-Justine
Montreal, Quebec, H3T 1C4
McGill University Health Center
Montreal, H4A 3J1
Ottawa Hospital, Division of Infectious Disease and Respirology
Ottawa, Ontario, K1H 8L6
Clinique d'asthme et d'allergie de Quebec
Québec, G1V 4M6
The Hospital for Sick Children
Toronto, M5G 1X8

Other trials in Canada

About this study

Official title: An Open-label, Multi-center Study to Evaluate the Safety and Pharmacokinetics of IGSC 20% Administered for 6 Months in Subjects With Primary Immunodeficiency

This study was designed to determine a dose of weekly subcutaneously administered Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (Grifols) (IGSC 20%) that produces steady-state AUC of total IgG that was non-inferior to that of the regularly administered intravenous dose of Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified (Grifols) (IGIV-C 10%) in primary immunodeficiency subjects. This study was also designed to determine steady state trough total IgG levels after IGSC 20% infusion and after IGIV-C 10% infusion for comparison and to assess the safety and tolerability of IGSC 20%.

Read the detailed description

This was a prospective, multi-center, open-label, single-sequence, 6-month, pharmacokinetic, safety and tolerability study of IGSC 20% in subjects with primary immunodeficiency. Approximately 50 subjects were to be enrolled in order to have approximately 30 adult subjects and 12 to 18 pediatric subjects (age 2-16 years) completing treatment with subcutaneously administered IGSC 20%.

This study included 3 treatment phases: Run-In Phase, IV Phase (IV administration of IGIV-C 10% treatment), and SC Phase (SC administration of IGSC 20%).

Subjects, depending on their current IgG treatment regimen, might be required to enter the Run-In Phase to receive IV IGIV-C 10% treatment (Sponsor provided) to achieve an approximately steady-state condition prior to entering the IV Phase. They then entered the IV Phase to determine the AUC profiles of IV infusions of IGIV-C 10%.

Subjects with a qualifying IV IGIV-C 10% treatment regimen (on stable IGIV-C 10% doses of 300-800 mg/kg) entered the IV Phase directly where they will receive IGIV-C 10%. In the IV Phase, steady-state IV PK assessments, including AUC, were to be performed.

After completing the IV Phase, subjects entered the SC Phase to receive weekly SC doses of IGSC 20% for at least 24 weeks.

The PK profiles of total IgG following administration of both IV (IGIV-C 10%) administration and SC (IGSC 20%) administration were determined and compared after reaching approximate steady-state conditions.

Conditions: Primary Immunodeficiency
Being tested: IGIV-C 10%, IGSC 20%
Medical subject headings: Primary Immunodeficiency Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

IGIV-C 10%Biological
Also called Immune Globulin Injection 10% Caprylate/Chromatography
IGIV-C 10% infusions every 3 to 4 weeks based on previous IgG regimen
IGSC 20%Biological
Also called Immune Globulin Subcutaneous 20% Caprylate/Chromatography
IGSC 20% weekly infusions with dose calculated based on previous IgG regimen

Study groups in NCT02604810
Study group	Role	What they receive
IGIV-C 10%	Active comparator	IV dose of Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified (Grifols) Receives: Biological: IGIV-C 10%
IGSC 20%	Experimental	Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (Grifols) Receives: Biological: IGSC 20%

What is being measured

The primary outcome is the main question the study is designed to answer.

AUC in the IV Phase and SC Phases: Steady-state AUC of Total IgG Over a Regular Dosing Interval
The primary PK endpoint (steady-state AUC values) analysis was performed using analysis of variance (ANOVA) using PK data from a total of 49 subjects from the IV phase and 39 subjects from the SC phase.
Measured: For intravenous infusion, predose, 0,1,3-16 hours and 1,2,3,5,7,14,21 or 28 days (2, 7, 21, or 28 days for pediatric subjects) post-dose and for subcutaneous infusion, pre-dose,1,3,4,5,7 days (3 and 7 days for pediatric subjects) post-dose

Secondary outcomes (1)

Mean Steady-state Trough (Pre-dose) Concentration of Total IgG Following IV Administration of IGIV-C 10% or SC Administration of IGSC 20%
Measured: For intravenous infusion, pre-dose at Week 1 and Week 3 or Week 4 and for subcutaneous infusion, predose at Weeks 13, 14, 17, and 21

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jan 2016Dec 2017

First posted13 Nov 2015 (estimated)
Study startJan 2016
Primary completionSep 2017
Study completionDec 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Primary ImmunodeficiencyStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 53 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02604810
Sponsor's protocol ID: GTI1502
Status last verified: Sep 2018
First submitted: 6 Nov 2015
Last updated: 4 Oct 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Sleasman JW, Lumry WR, Hussain I, Wedner HJ, Harris JB, Courtney KL, Mondou E, Lin J, Stein MR. Immune globulin subcutaneous, human - klhw 20% for primary humoral immunodeficiency: an open-label, Phase III study. Immunotherapy. 2019 Nov;11(16):1371-1386. doi: 10.2217/imt-2019-0159. Epub 2019 Oct 17.
PubMed 31621458

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Natural History of Bronchiectasis
Bronchiectasis, Cystic Fibrosis
RecruitingObservational study
Leukapheresis Procedures to Obtain Plasma and Lymphocytes for Research Studies on Antiretroviral Naive HIV-1 Research Participants
HIV
RecruitingObservational study
Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES)
Infections, Pneumonia
RecruitingObservational study
Genetic Basis of Immunodeficiency
Severe Combined Immunodeficiency
RecruitingObservational study
Detection and Characterization of Infections and Infection Susceptibility
Immune Deficiencies

All Primary Immunodeficiency trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: An Open-label, Multi-center Study to Evaluate the Safety and Pharmacokinetics of IGSC 20% Administered for 6 Months in Subjects With Primary Immunodeficiency
ClinicalTrials.gov ID: NCT02604810
Acronym / sponsor ID: GTI1502
Conditions: Primary Immunodeficiency
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 53 participants (actual)
Lead sponsor: Grifols Therapeutics LLCIndustry (pharma, biotech, devices)
Study start: Jan 2016 (actual)
Primary completion: Sep 2017 (actual)
Study completion: Dec 2017 (actual)
First posted: 13 Nov 2015 (estimated)
Results: Posted 4 Oct 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

This study included 3 treatment phases: Run-In Phase, IV Phase (IV administration of IGIV-C 10% treatment), and SC Phase (SC administration of IGSC 20%).

After completing the IV Phase, subjects entered the SC Phase to receive weekly SC doses of IGSC 20% for at least 24 weeks.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
IGIV-C 10%	Active comparator	Biological: IGIV-C 10%IV dose of Immune Globulin Injection (Human), 10% Caprylate/Chromatography Purified (Grifols)
IGSC 20%	Experimental	Biological: IGSC 20%Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (Grifols)

Who may qualify

Ages: 2 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (4 listed)

Pre-existing diagnosis of primary immunodeficiency with features of hypogammaglobulinemia requiring IgG replacement therapy
No serious bacterial infection within the last 3 months prior to or during Screening
Currently on IgG replacement therapy (via IV or SC infusion) for ≥3 consecutive months. Subjects receiving IGIV must be receiving a dosage of 300 to 800 mg/kg per infusion
Documented (at least once within previous 3 months) IgG trough level of ≥500 mg/dL on current IgG replacement therapy regimen

Key exclusion criteria (9 listed)

Known serious adverse reaction to immunoglobulin or any severe anaphylactic reaction to blood or any blood-derived product
History of blistering skin disease, clinically significant thrombocytopenia, bleeding disorder, diffuse rash, recurrent skin infections, or other disorders where SC therapy would be contraindicated during the study
Isolated IgG subclass deficiency, isolated specific antibody deficiency disorder, or transient hypogammaglobulinemia of infancy
Nephrotic syndrome, and/or a history of acute renal failure and/or severe renal impairment, and/or on dialysis
History (year prior to Screening or 2 episodes in lifetime ) of or current diagnosis of deep venous thrombosis or thromboembolism (eg, deep vein thrombosis, myocardial infarction, cerebrovascular accident or transient ischemic attack)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
IGIV-C 10%Also: Immune Globulin Injection 10% Caprylate/ChromatographyIGIV-C 10% infusions every 3 to 4 weeks based on previous IgG regimen	Biological	IGIV-C 10%
IGSC 20%Also: Immune Globulin Subcutaneous 20% Caprylate/ChromatographyIGSC 20% weekly infusions with dose calculated based on previous IgG regimen	Biological	IGSC 20%

Primary outcome

AUC in the IV Phase and SC Phases: Steady-state AUC of Total IgG Over a Regular Dosing Interval
Time frame: For intravenous infusion, predose, 0,1,3-16 hours and 1,2,3,5,7,14,21 or 28 days (2, 7, 21, or 28 days for pediatric subjects) post-dose and for subcutaneous infusion, pre-dose,1,3,4,5,7 days (3 and 7 days for pediatric subjects) post-dose
The primary PK endpoint (steady-state AUC values) analysis was performed using analysis of variance (ANOVA) using PK data from a total of 49 subjects from the IV phase and 39 subjects from the SC phase.

1 secondary outcome

Mean Steady-state Trough (Pre-dose) Concentration of Total IgG Following IV Administration of IGIV-C 10% or SC Administration of IGSC 20%
Time frame: For intravenous infusion, pre-dose at Week 1 and Week 3 or Week 4 and for subcutaneous infusion, predose at Weeks 13, 14, 17, and 21

Results and safety

Results posted to the registry on 4 Oct 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
IGIV-C 10% First, IGSC 20% Second	52	49

Primary outcome: AUC in the IV Phase and SC Phases: Steady-state AUC of Total IgG Over a Regular Dosing Interval

Time frame: For intravenous infusion, predose, 0,1,3-16 hours and 1,2,3,5,7,14,21 or 28 days (2, 7, 21, or 28 days for pediatric subjects) post-dose and for subcutaneous infusion, pre-dose,1,3,4,5,7 days (3 and 7 days for pediatric subjects) post-dose. Geometric mean (90% Confidence Interval). Unit: h*mg/dL

Measure	IGIV-C 10% n = 49	IGSC 20% n = 39
Value	207921.5 (197865.8 to 218488.2)	213141.4 (200568.6 to 226502.3)

IGIV-C 10% vs IGSC 20%: Geometric least-squares mean ratio: 1.04 (90% CI 1.00 to 1.07)

Population analysed: The PK population consisted of all subjects who received study drugs and had sufficient and valid total IgG concentration versus time data for either the IV or SC Phase to allow calculation of AUC0-τ,SC or AUC0-τ,IV (the primary PK endpoint).

1 secondary outcome is reported in the full results.

Adverse events

Time frame: During the IV phase, the adverse event data were collected for 4 to 5 weeks. During the SC phase, the adverse event data were collected for 24 weeks.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
IGIV-C 10%	1 of 52 (1.9%)	6 of 52 (11.5%)	0 of 52
IGSC 20%	2 of 49 (4.1%)	35 of 49 (71.4%)	0 of 49

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31621458Sleasman JW, Lumry WR, Hussain I, Wedner HJ, Harris JB, Courtney KL, Mondou E, Lin J, Stein MR. Immune globulin subcutaneous, human - klhw 20% for primary humoral immunodeficiency: an open-label, Phase III study. Immunotherapy. 2019 Nov;11(16):1371-1386. doi: 10.2217/imt-2019-0159. Epub 2019 Oct 17.

Related trials for Primary Immunodeficiency

RecruitingObservational study
Natural History of Bronchiectasis
Bronchiectasis, Cystic Fibrosis
RecruitingObservational study
Leukapheresis Procedures to Obtain Plasma and Lymphocytes for Research Studies on Antiretroviral Naive HIV-1 Research Participants
HIV
RecruitingObservational study
Natural History, Management, and Genetics of the Hyperimmunoglobulin E Recurrent Infection Syndrome (HIES)
Infections, Pneumonia
RecruitingObservational study
Genetic Basis of Immunodeficiency
Severe Combined Immunodeficiency
RecruitingObservational study
Detection and Characterization of Infections and Infection Susceptibility
Immune Deficiencies

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

25 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing IGIV-C 10% and IGSC 20% in people with Primary Immunodeficiency, run by Grifols Therapeutics LLC at 25 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Oct 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

AUC in the IV Phase and SC Phases: Steady-state AUC of Total IgG Over a Regular Dosing Interval (time frame: For intravenous infusion, predose, 0,1,3-16 hours and 1,2,3,5,7,14,21 or 28 days (2, 7, 21, or 28 days for pediatric subjects) post-dose and for subcutaneous infusion, pre-dose,1,3,4,5,7 days (3 and 7 days for pediatric subjects) post-dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02604810, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2019.