A Phase 3 interventional study of Subgam in Primary Immune Deficiency Disorders, Common Variable Immunodeficiency and X-linked Agammaglobulinaemia, sponsored by Bio Products Laboratory. Completed at 16 sites in United States. Open to participants aged 2 Years to 75 Years. Per ClinicalTrials.gov, last updated 2018-09-12.
Sponsored by Bio Products Laboratory · Phase 3, Interventional, and Other
The main objective of the study is to determine the pharmacokinetics profile of Subgam-VF. The secondary objectives are to assess the safety of Subgam-VF and refine the dose adjustment coefficient for Subgam-VF needed for subjects switching from prior intravenous immunoglobulin (IGIV) therapy.
This will be a Phase III, multicenter, open-label, non-randomized study.
Following a screening period, eligible subjects will commence weekly Subgam-VF treatment; this is a 16% subcutaneous IgG product.
Subjects will receive Subgam-VF for 26 weeks during which time safety will be assessed.
After Week 21, PK sampling will commence.
Follow-up visit (one week after the last Subgam-VF infusion, Week 27). All AEs will be monitored up to 28 days after the last Subgam-VF infusion by telephone contact (Week 30).
Subgam-VF will be administered subcutaneously using infusion pumps.
Subjects will be given diaries to record adverse event data as well as any infusions administered at home. In addition there will be a telephone follow up by an appropriately qualified site staff member on day 3 after each site administered and home administered infusion to check for any adverse reactions including infusion site reactions and remind subjects to document these in their subject study diary.
211 studies on the registry are indexed under Primary Immunodeficiency Diseases; 51 are open to participants now.
This study's enrollment of 38 is close to the median of 36 across 125 interventional studies indexed under Primary Immunodeficiency Diseases.
Browse Primary Immunodeficiency Diseases studies →Bio Products Laboratory is the lead sponsor of 27 studies on the registry; none are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Currently receiving a licensed (or stage III, IIIb) IGIV or SCIG and
Exclusion Criteria:
Is positive for any of the following at screening:
Has levels at screening greater than 2.5 times the as defined at the central laboratory of any of the following:
Is receiving the following medication:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Subgam-VF is a 16% IgG and will be administered weekly, by subcutaneous infusion. The total duration of treatment will be for 26 weeks.
Biological: Subgam
Subgam-VF dose will be given as 1.37 of the established IGIV dose (expressed in mg/kg/week) for 26 weeks (26 infusions) beginning one week after the last IGIV infusion. Dose of Subgam-VF will then be adjusted based on the ratio of the Immunoglobulin G (IgG) average concentration achieved with Subgam-VF compared to IGIV.
Also known as: Subgam-VF
Data (Derived From Absolute Concentration) Were Pooled With Historical Data and a Treatment Variable Defined (Subgam-VF or Gammaplex 5% IGIV). Outcome Measure Defined as Log Transformed sAUC0-t Standardized to One Week.
Log transformed sAUC0-t, (AUC0-t standardized to one week) were analysed using a multiple linear regression model fitted including treatment, allowing for variability between treatment groups. The mean difference (Subgam-VF or Gammaplex IGIV 5%) between treatments with 90% Confidence Interval (CI) were back transformed to give an estimate of the ratio (Subgam-VF/ Gammaplex 5% IGIV) of sAUC(0-t). Data was collected at the following timepoints after week 21 of the clinical trial over a period of 1 week: Pre-dose on Day 0 and post-dose at days 1, 2, 3, 5 and 7.
Time frame: 1 week
Number of Participants Who Experienced AEs Based on Treatment-emergent AEs (TEAEs)
TEAEs defined as those events with onset date between the first infusion date and 28 days after the last infusion.
Time frame: 30 weeks
Dose Refinement in Switching From Gammaplex 5% IGIV to Subgam-VF
The initial weekly dose of Subgam-VF administered was calculated by taking the average weekly equivalent of the subject's IGIV dose, divided by the average dosing interval in weeks (i.e. 3 or 4), multiplied by 1.37, a dose adjustment coefficient based on other licensed subcutaneous IgG products. If the subject was already receiving a weekly SCIG IgG there will be no dose adjustment. A refined dose adjustment was estimated as 1.37/the ratio (Subgam-VF/ Gammaplex 5% IGIV) of geometric means for sAUC0-t and presented with 90% CI.
Time frame: Week 26
Number of Infusion Site Reactions
Infusion site reactions are defined as those events with onset date between the first infusion date and 28 days after the last infusion.
Time frame: 30 weeks
Population PK Model for IgG in PID Patients for Alternative Dosing Schedules.
Develop a population pharmacokinetic (PK) model for IgG in PID patients following IV (Gammaplex 5%) or SC (Subgam-VF) administration; * Conduct a formal covariate analysis to assess the impact of patient demographics, and disease-related factors on the PK of IgG following IV or SC administration and to identify those patient covariates which may be utilized in or require dose adjustment; * Use the final population PK model to simulate serum IgG concentration-time profiles in a population of PID patients in order to: * Assess switching from various IgG IV and SC dosing regimens; and * Derive the weight-adjusted dose increment required to achieve a specified difference in serum IgG trough levels when Subgam-VF is administered either weekly or biweekly
Time frame: 30 months
| Milestone | Subgam-VF |
|---|---|
| Started | 38 |
| Completed | 33 |
| Not completed | 5 |
| Withdrew: Withdrawal by subject | 3 |
| Withdrew: Withdrew consent due to aes | 1 |
| Withdrew: Precautionary measure | 1 |
Log transformed sAUC0-t, (AUC0-t standardized to one week) were analysed using a multiple linear regression model fitted including treatment, allowing for variability between treatment groups. The mean difference (Subgam-VF or Gammaplex IGIV 5%) between treatments with 90% Confidence Interval (CI) were back transformed to give an estimate of the ratio (Subgam-VF/ Gammaplex 5% IGIV) of sAUC(0-t). Data was collected at the following timepoints after week 21 of the clinical trial over a period of 1 week: Pre-dose on Day 0 and post-dose at days 1, 2, 3, 5 and 7.
| Ratio | Subgam-VF and Gammaplex 5% |
|---|---|
| Data (Derived From Absolute Concentration) Were Pooled With Historical Data and a Treatment Variable Defined (Subgam-VF or Gammaplex 5% IGIV). Outcome Measure Defined as Log Transformed sAUC0-t Standardized to One Week. | 0.98 (0.91 to 1.05) |
TEAEs defined as those events with onset date between the first infusion date and 28 days after the last infusion.
| Participants | Subgam-VF |
|---|---|
| Any TEAE | 36 |
| No TEAE | 2 |
| Discontinued because of TEAEs | 1 |
| Product Related TEAE | 15 |
| No Product Related TEAEs | 23 |
| SAE | 0 |
The initial weekly dose of Subgam-VF administered was calculated by taking the average weekly equivalent of the subject's IGIV dose, divided by the average dosing interval in weeks (i.e. 3 or 4), multiplied by 1.37, a dose adjustment coefficient based on other licensed subcutaneous IgG products. If the subject was already receiving a weekly SCIG IgG there will be no dose adjustment. A refined dose adjustment was estimated as 1.37/the ratio (Subgam-VF/ Gammaplex 5% IGIV) of geometric means for sAUC0-t and presented with 90% CI.
| Ratio | Subgam-VF and Gammaplex 5% |
|---|---|
| Dose Refinement in Switching From Gammaplex 5% IGIV to Subgam-VF | 1.33 (1.23 to 1.44) |
Infusion site reactions are defined as those events with onset date between the first infusion date and 28 days after the last infusion.
| infusion site reactions | Subgam-VF |
|---|---|
| Number of Infusion Site Reactions | 447 |
Develop a population pharmacokinetic (PK) model for IgG in PID patients following IV (Gammaplex 5%) or SC (Subgam-VF) administration; * Conduct a formal covariate analysis to assess the impact of patient demographics, and disease-related factors on the PK of IgG following IV or SC administration and to identify those patient covariates which may be utilized in or require dose adjustment; * Use the final population PK model to simulate serum IgG concentration-time profiles in a population of PID patients in order to: * Assess switching from various IgG IV and SC dosing regimens; and * Derive the weight-adjusted dose increment required to achieve a specified difference in serum IgG trough levels when Subgam-VF is administered either weekly or biweekly
| % of predicted change in IgG trough | Subgam-VF |
|---|---|
| Increase from IGIV to Weekly Subgam | 31 |
| Increase from IGIV to Biweekly Subgam | 22 |
| Decrease from Weekly Subgam to Biweekly Subgam | 7 |
| Increase from Weekly Subgam to twice weekly Subgam | 2 |
| Increase from Weekly Subgam to 3x weekly Subgam | 3 |
| Increase from weekly Subgam to 5x weekly Subgam | 3 |
| Increase from weekly Subgam to 7x weekly Subgam | 3 |
Collected over 7 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Subgam-VF | 0/38 (0%) | 0/38 (0%) | 36/38 (94.7%) |
| Event | Subgam-VF |
|---|---|
| NasopharyngitisInfections and infestations | 10/38 |
| DiarrhoeaGastrointestinal disorders | 8/38 |
| HeadacheNervous system disorders | 8/38 |
| Infusion Site ErythemaGeneral disorders | 6/38 |
| Infusion Site PainGeneral disorders | 6/38 |
| PyrexiaGeneral disorders | 6/38 |
| Viral Upper Respiratory Tract InfectionInfections and infestations | 5/38 |
| CoughRespiratory, thoracic and mediastinal disorders | 5/38 |
| Infusion Site PruritusGeneral disorders | 4/38 |
| Acute SinusitisInfections and infestations | 4/38 |
All subjects
| Age, Customized(Participants) | Subgam-VF |
|---|---|
| >=16 years | 25 |
| < 16 years | 13 |
| Sex: Female, Male(Participants) | Subgam-VF |
|---|---|
| Female | 22 |
| Male | 16 |
| Ethnicity (NIH/OMB)(Participants) | Subgam-VF |
|---|---|
| Hispanic or Latino | 2 |
| Not Hispanic or Latino | 36 |
| Unknown or Not Reported | 0 |
| Race (NIH/OMB)(Participants) | Subgam-VF |
|---|---|
| American Indian or Alaska Native | 1 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 0 |
| White | 35 |
| More than one race | 1 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(Participants) | Subgam-VF |
|---|---|
| United States | 38 |
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Aug 2015 to primary completion in May 2017, 21 months.
Results were first posted in Sep 2018, 1 year 3 months after primary completion.
Of 25 phase 3 interventional studies under Primary Immunodeficiency Diseases, half reached primary completion within 35 months of starting (the median), counting those still running; a quarter within 19 and three quarters within 41. This study's 21 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Aug 2018. You cannot join it, but the record below documents what was studied.
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Primary Immunodeficiency Diseases →
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