Primary ImmunodeficiencyPhase 3NCT02806986
Efficacy, Pharmacokinetics, Safety, and Tolerability of IGSC 20% in Subjects With Primary Immunodeficiency
A Phase 3 study testing IGSC 20% in people with Primary Immunodeficiency, run by Grifols Therapeutics LLC at 23 sites in 9 countries.
Trial summary
Approximately 60 subjects will be enrolled in order to have approximately 20 adult subjects and 20 pediatric subjects treated with subcutaneously administered Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (IGSC 20%) who complete the entire study. Read more about this study
- Who is it for?
- Ages 2 to 75 years
- Conditions the study is for
- Primary Immunodeficiency
- What is being tested?
- IGSC 20%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 61 participants
- Where
- 23 sitesin 9 countries
- Study dates
- Jun 2016to 15 May 2019
- 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 PI with features of hypogammaglobulinemia requiring IgG replacement therapy
- No serious bacterial infection within the 3 months prior to Screening and has no serious bacterial infections (SBIs) up to the time of the Baseline Visit
- Currently on IgG replacement therapy (stable regimen [dose and dosing interval] via IV or SC infusion) for ≥ 3 consecutive months at a dosage of at least 200 mg/kg per infusion
- Documented (within previous 3 months) of an IgG trough level of ≥ 500 mg/dL on current IgG replacement therapy regimen
- Screening/pre-Baseline trough IgG levels must be ≥ 500 mg/dL.
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 is on dialysis
- Known previous infection with or clinical signs and symptoms consistent with current hepatitis B virus or hepatitis C virus infection
- History of (year prior to Screening or 2 episodes in lifetime) or current diagnosis of deep venous thrombosis or thromboembolism (e.g., myocardial infarction, cerebrovascular accident, or transient ischemic attack)
Show all 10Show fewer
- 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
- HIV positive by nucleic acid amplification technology based on a Screening blood sample
- Uncontrolled arterial hypertension (adult subjects: systolic blood pressure > 160 mmHg and/or diastolic blood pressure > 100 mmHg)
- 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
23 sites in 9 countries.
23 sites in 9 countries
Spain7 sites
Hospital Universitario Vall d'Hebron
Barcelona, 08025
Vall d'Hebron University Hospital
Barcelona, 08035
Hospital Universitari Sant Joan de Déu
Barcelona, 08950
Hospital Universitario Reina Sofia
Córdoba, 14004
Hospital Clinico San Carlos
Madrid, 28040
Hospital 12 Octubre
Madrid, 28041
Hospital Virgen del Rocio
Seville, 41013
Germany5 sites
Klinikum Dortmund gGmbH
Dortmund, 44137
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246
Children's Hospital at Municipal Hospital St. Georg
Leipzig, 04129
University Hospital of Mainz
Mainz, 55131
Asklepios Klinik Sankt Augustin
Sankt Augustin, 53757
United Kingdom3 sites
Addenbrooke's Hospital
Cambridge, CB2 0QQ
St Bartholomew's Hospital
London, E1 2ES
Derriford Hospital
Plymouth, PL6 8DH
Australia2 sites
Wesley Medical Research
Auchenflower, 4066
Royal Melbourne Hospital
Parkville, 3050
Hungary2 sites
United St Istvan and St Laszlo Hospital
Budapest
Josa Andras County Hospital
Nyiregyháza, H-4400
About this study
Official title: A Multi-Center, Open-Label, Single-Arm Trial to Evaluate Efficacy, Pharmacokinetics, and Safety and Tolerability of IGSC 20% in Subjects With Primary Immunodeficiency
Approximately 60 subjects will be enrolled in order to have approximately 20 adult subjects and 20 pediatric subjects treated with subcutaneously administered Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (IGSC 20%) who complete the entire study. This study will include 3 study stages: Screening/Previous Regimen Phase, IGSC 20% Treatment Stage 1 (13 IGSC 20% weekly doses), and IGSC 20% Treatment Stage 2 (39 IGSC 20% weekly doses). A total of 52 doses of IGSC 20% will be administered with a final follow-up visit 1 week after the last dose at Week 53. Subjects/caregivers will be trained on self-administration of IGSC 20% by the clinical site personnel.
Read the detailed description
This is a prospective, multi-center, open-label, single-arm, efficacy, PK, safety and tolerability study of IGSC 20% in subjects with PI. Approximately 60 subjects will be enrolled in order to have approximately 20 adult subjects and 20 pediatric subjects treated with subcutaneously administered IGSC 20% who complete the entire study.
This study will include 3 study stages: Screening/Previous Regimen Phase, IGSC 20% Treatment Stage 1 (13 IGSC 20% weekly doses), and IGSC 20% Treatment Stage 2 (39 IGSC 20% weekly doses).
Previous Regimen Phase: Subjects will be infused with their current ongoing ("previous regimen") intravenous immune globulin/subcutaneous immune globulin (IVIG/SCIG) regimen (pIV/pSC) in the clinic to obtain 2 trough immunoglobulin G (IgG) levels (obtained prior to each pIV/pSC infusion) on each subject's "previous regimen".
20% IGSC Treatment Stage 1: The first dose of IGSC 20% will be administered at the clinical site immediately after Baseline assessments are complete (SC#1). All subjects will receive 13 IGSC 20% infusions at weekly intervals. IgG trough blood levels will be measured at all (except SC#3) study visits All other doses of IGSC 20% may be infused at home (once properly trained) or in the clinic. The Treatment Stage 1 dose will continue into IGSC 20% Treatment Stage 2.
IGSC 20% Treatment Stage 2: The IGSC 20% dose (mg/kg) will remain constant with no dose adjustment permitted in this phase, unless it is absolutely medically necessary. While all subjects will have a SC#17 clinic visit and standard assessments, serial pharmacokinetics (PK) sampling will only be performed in a subset of adult subjects:
- Conditions
- Primary Immunodeficiency
- Being tested
- 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.
IGSC 20%Biological
Also called Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography
Weekly administration of IGSC 20% via intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| IGSC 20% | Experimental | 13 doses of IGSC 20% in Treatment Stage 1 and 39 doses of IGSC 20% in Treatment Stage 2 for a total of 52 doses if IGSC 20% Receives: Biological: IGSC 20% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Serious Bacterial Infection (SBI) Per Participant Per Year
The rate of SBI events per participant per year during IGSC 20% treatment was calculated as the total number of SBI events divided by the total duration of exposure in years across all participants. The 2-sided 98% confidence interval (CI) was determined from a generalized linear model for poisson regression for the log-transformed number of events with log-transformed duration of exposure in years as an offset variable.
Measured: IGSC 20% Treatment Stage 1: Week 1 to 13; IGSC 20% Treatment Stage 2: Week 14 to 53; IGSC 20% Overall: Week 1 to 53
Secondary outcomes (5)
Mean Trough Total IgG Concentration
Mean trough total IgG concentration during the previous regimen phase was calculated as the average of the trough concentrations at the previous IVIG (pIV)#1 and pIV#2 visits for participants entering the study on a previous IVIG regimen, or at the previous subcutaneous immune globulin (SCIG) (pSC)#1 and baseline/SC#1 visits for participants entering the study on a previous SCIG regimen. Mean trough total IgG concentration during the IGSC 20% phase was calculated as the average of all steady state trough concentrations measured during the IGSC 20% treatment stage 2 at the visits corresponding to Weeks 17, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52 and 53.
Measured: Previous Regimen Phase: 2 timepoints pre-dose of pIV or pSC between Screening and Baseline (up to 8 weeks). IGSC 20% Phase: Pre-dose of IGSC 20% at Baseline (Week 1), Weeks 2, 5, 9, 13, 17, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Week 53
Rate of Infection of Any Kind Per Participant Per Year
The total number of infections of any kind (serious/non-serious including acute sinusitis, exacerbation of chronic sinusitis, acute otitis media, pneumonia, acute bronchitis, infectious diarrhea, etc.) as determined by the investigator were evaluated. The rate of infection events per participant per year during IGSC 20% treatment was calculated as the total number of infection events divided by the total duration of exposure in years across all participants. The 2-sided 95% CI was determined from a generalized linear model for poisson regression for the log-transformed number of events with log-transformed duration of exposure in years as an offset variable.
Measured: IGSC 20% Treatment Stage 1: Week 1 to 13; IGSC 20% Treatment Stage 2: Week 14 to 53; IGSC 20% Overall: Week 1 to 53
Rate of Days on Antibiotics Per Participants Per Year
The rate of days on antibiotics per participants per year during IGSC 20% treatment was calculated as the total number of days on antibiotic divided by the total duration of exposure in years across all participants. The 2-sided 95% CI was determined from a generalized linear model for poisson regression for the log transformed number of days with log-transformed duration of exposure in years as an offset variable.
Measured: IGSC 20% Treatment Stage 1: Week 1 to 13; IGSC 20% Treatment Stage 2: Week 14 to 53; IGSC 20% Overall: Week 1 to 53
Rate of Hospitalization Due to Infection Per Participants Per Year
The rate of hospitalization due to infection events per participant per year during IGSC 20% treatment was calculated as the total number of hospitalization due to infection events divided by the total duration of exposure in years across all participants. The 2-sided 95% CI was determined from a generalized linear model for poisson regression for the log-transformed number of events with log-transformed duration of exposure in years as an offset variable.
Measured: IGSC 20% Treatment Stage 1: Week 1 to 13; IGSC 20% Treatment Stage 2: Week 14 to 53; IGSC 20% Overall: Week 1 to 53
Rate of Days of Work/School/Daily Activities Missed Per Participants Per Year Due to Infections and Related Treatment
The rate of days of work, school or daily activities missed per participant per year during IGSC 20% treatment was calculated as the total number of days of work/school/daily activities missed divided by the total duration of exposure in years across all participants. The 2-sided 95% CI was determined from a generalized linear model for poisson regression for the log-transformed number of days with log transformed duration of exposure in years as an offset variable.
Measured: IGSC 20% Treatment Stage 1: Week 1 to 13; IGSC 20% Treatment Stage 2: Week 14 to 53; IGSC 20% Overall: Week 1 to 53
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2016 (estimated)
- Study startJun 2016
- Primary completion15 May 2019
- Study completion15 May 2019
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.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 61 participants (actual)
Sponsor and investigators
- Lead sponsor
- Grifols Therapeutics LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02806986
- Sponsor's protocol ID
- GTI1503
- Other IDs
- 2015-003290-15, 2015
- Status last verified
- Jun 2020
- First submitted
- 3 Jun 2016
- Last updated
- 16 Jun 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-Center, Open-Label, Single-Arm Trial to Evaluate Efficacy, Pharmacokinetics, and Safety and Tolerability of IGSC 20% in Subjects With Primary Immunodeficiency
- ClinicalTrials.gov ID
- NCT02806986
- Acronym / sponsor ID
- GTI1503
- Conditions
- Primary Immunodeficiency
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- Grifols Therapeutics LLCIndustry (pharma, biotech, devices)
- Study start
- Jun 2016 (actual)
- Primary completion
- 15 May 2019 (actual)
- Study completion
- 15 May 2019 (actual)
- First posted
- 21 Jun 2016 (estimated)
- Results
- Posted 16 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Approximately 60 subjects will be enrolled in order to have approximately 20 adult subjects and 20 pediatric subjects treated with subcutaneously administered Immune Globulin Subcutaneous (Human), 20% Caprylate/Chromatography Purified (IGSC 20%) who complete the entire study. This study will include 3 study stages: Screening/Previous Regimen Phase, IGSC 20% Treatment Stage 1 (13 IGSC 20% weekly doses), and IGSC 20% Treatment Stage 2 (39 IGSC 20% weekly doses). A total of 52 doses of IGSC 20% will be administered with a final follow-up visit 1 week after the last dose at Week 53. Subjects/caregivers will be trained on self-administration of IGSC 20% by the clinical site personnel.
Detailed description
This is a prospective, multi-center, open-label, single-arm, efficacy, PK, safety and tolerability study of IGSC 20% in subjects with PI. Approximately 60 subjects will be enrolled in order to have approximately 20 adult subjects and 20 pediatric subjects treated with subcutaneously administered IGSC 20% who complete the entire study.
This study will include 3 study stages: Screening/Previous Regimen Phase, IGSC 20% Treatment Stage 1 (13 IGSC 20% weekly doses), and IGSC 20% Treatment Stage 2 (39 IGSC 20% weekly doses).
Previous Regimen Phase: Subjects will be infused with their current ongoing ("previous regimen") intravenous immune globulin/subcutaneous immune globulin (IVIG/SCIG) regimen (pIV/pSC) in the clinic to obtain 2 trough immunoglobulin G (IgG) levels (obtained prior to each pIV/pSC infusion) on each subject's "previous regimen".
20% IGSC Treatment Stage 1: The first dose of IGSC 20% will be administered at the clinical site immediately after Baseline assessments are complete (SC#1). All subjects will receive 13 IGSC 20% infusions at weekly intervals. IgG trough blood levels will be measured at all (except SC#3) study visits All other doses of IGSC 20% may be infused at home (once properly trained) or in the clinic. The Treatment Stage 1 dose will continue into IGSC 20% Treatment Stage 2.
IGSC 20% Treatment Stage 2: The IGSC 20% dose (mg/kg) will remain constant with no dose adjustment permitted in this phase, unless it is absolutely medically necessary. While all subjects will have a SC#17 clinic visit and standard assessments, serial pharmacokinetics (PK) sampling will only be performed in a subset of adult subjects:
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| IGSC 20% | Experimental | Biological: IGSC 20%13 doses of IGSC 20% in Treatment Stage 1 and 39 doses of IGSC 20% in Treatment Stage 2 for a total of 52 doses if IGSC 20% |
Who may qualify
- Ages
- 2 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Pre-existing diagnosis of PI with features of hypogammaglobulinemia requiring IgG replacement therapy
- No serious bacterial infection within the 3 months prior to Screening and has no serious bacterial infections (SBIs) up to the time of the Baseline Visit
- Currently on IgG replacement therapy (stable regimen [dose and dosing interval] via IV or SC infusion) for ≥ 3 consecutive months at a dosage of at least 200 mg/kg per infusion
- Documented (within previous 3 months) of an IgG trough level of ≥ 500 mg/dL on current IgG replacement therapy regimen
- Screening/pre-Baseline trough IgG levels must be ≥ 500 mg/dL.
Key exclusion criteria (10 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 is on dialysis
- Known previous infection with or clinical signs and symptoms consistent with current hepatitis B virus or hepatitis C virus infection
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 |
|---|---|---|
| IGSC 20%Also: Immune Globulin Subcutaneous (Human), 20% Caprylate/ChromatographyWeekly administration of IGSC 20% via intravenous infusion | Biological | IGSC 20% |
Primary outcome
Rate of Serious Bacterial Infection (SBI) Per Participant Per Year
Time frame: IGSC 20% Treatment Stage 1: Week 1 to 13; IGSC 20% Treatment Stage 2: Week 14 to 53; IGSC 20% Overall: Week 1 to 53
The rate of SBI events per participant per year during IGSC 20% treatment was calculated as the total number of SBI events divided by the total duration of exposure in years across all participants. The 2-sided 98% confidence interval (CI) was determined from a generalized linear model for poisson regression for the log-transformed number of events with log-transformed duration of exposure in years as an offset variable.
5 secondary outcomes
Mean Trough Total IgG Concentration
Time frame: Previous Regimen Phase: 2 timepoints pre-dose of pIV or pSC between Screening and Baseline (up to 8 weeks). IGSC 20% Phase: Pre-dose of IGSC 20% at Baseline (Week 1), Weeks 2, 5, 9, 13, 17, 18, 20, 24, 28, 32, 36, 40, 44, 48, 52, and at Week 53
Rate of Infection of Any Kind Per Participant Per Year
Time frame: IGSC 20% Treatment Stage 1: Week 1 to 13; IGSC 20% Treatment Stage 2: Week 14 to 53; IGSC 20% Overall: Week 1 to 53
Rate of Days on Antibiotics Per Participants Per Year
Time frame: IGSC 20% Treatment Stage 1: Week 1 to 13; IGSC 20% Treatment Stage 2: Week 14 to 53; IGSC 20% Overall: Week 1 to 53
Rate of Hospitalization Due to Infection Per Participants Per Year
Time frame: IGSC 20% Treatment Stage 1: Week 1 to 13; IGSC 20% Treatment Stage 2: Week 14 to 53; IGSC 20% Overall: Week 1 to 53
Rate of Days of Work/School/Daily Activities Missed Per Participants Per Year Due to Infections and Related Treatment
Time frame: IGSC 20% Treatment Stage 1: Week 1 to 13; IGSC 20% Treatment Stage 2: Week 14 to 53; IGSC 20% Overall: Week 1 to 53
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
23 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing IGSC 20% in people with Primary Immunodeficiency, run by Grifols Therapeutics LLC at 23 sites in 9 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 5 inclusion and 10 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 16 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in Spain, Germany, United Kingdom, Australia, Hungary and 4 more countries. 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 16 Jun 2020). 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?
Rate of Serious Bacterial Infection (SBI) Per Participant Per Year (time frame: IGSC 20% Treatment Stage 1: Week 1 to 13; IGSC 20% Treatment Stage 2: Week 14 to 53; IGSC 20% Overall: Week 1 to 53). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Jun 2020.