CVI - Common Variable ImmunodeficiencyPhase 4NCT03576469
A Study to Evaluate the Benefit of RUCONEST® in Subjects Who Experience ADRs Related to IVIG Infusions
A Phase 4 study testing C1-esterase inhibitor [recombinant] (C1-INH-R) in people with CVI - Common Variable Immunodeficiency, run by IMMUNOe Research Centers at 1 site in United States.
Trial summary
Patients receiving intravenous immunoglobulin (IVIG) therapy for primary immunodeficiency and neurologic conditions may experience adverse drug reactions (ADRs). The mechanism of the ADR is unknown. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- CVI - Common Variable Immunodeficiency
- What is being tested?
- C1-esterase inhibitor [recombinant] (C1-INH-R)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jun 2018to 1 Mar 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 years and older experiencing ADRs related to IVIG infusions
- Stable dose of IVIG for 3 months
- Willing to comply with all aspects of the protocol, including blood draws
- Female patients of childbearing potential who are sexually active must be willing to use an acceptable form of contraception. Acceptable forms of contraception are defined as those with a failure rate < 1% when properly applied and include: a combination oral pill, some intra-uterine devices, and a sterilized partner in a stable relationship. Female patients must not be pregnant, planning to become pregnant, or be actively breastfeeding through the entire study period.
Who cannot join
- Receiving treatment for HAE, either prophylactic or acute therapy
- Patients with medical history of allergy to rabbits or rabbit-derived products (including rhC1INH)
- Patients who are pregnant, or breastfeeding, or are currently intending to become pregnant.
- Patients who, in the investigator's opinion, might not be suitable for the trial
Trial locations and contacts
1 site in 1 country.
United States1 site
IMMUNOe Research Centers
Centennial, Colorado, 80112
About this study
Official title: A Single-site, Open-Label, Pilot Study to Evaluate the Benefit of RUCONEST® in Subjects Who Experience ADRs Related to IVIG Infusions
Patients receiving intravenous immunoglobulin (IVIG) therapy for primary immunodeficiency and neurologic conditions may experience adverse drug reactions (ADRs). The mechanism of the ADR is unknown. Currently, the standard practice for these patients is to change from IV to subcutaneous IG (SCIG) but because of the need of immunomodulation or patient preference, SCIG may not be an option. Data has shown that some levels of complement decrease from pre- to post-infusion of IVIG. This study is to determine if replacing this complement protein may ameliorate ADRs.
Read the detailed description
This is a single-site, pilot study conducted in the US to determine the benefit of human C1-esterase inhibitor [recombinant] (C1-INH-R) therapy to ameliorate ADRs in subjects receiving IVIG therapy experience ADRs post-infusion. Subjects who are currently receiving IVIG for immunodeficiency or neurologic conditions and experience ADRs will be enrolled.
In part 1, subjects will continue to receive IVIG for two infusions. Complement proteins will be measured pre- and post-infusion. Quality of life and other questionnaires will be administered.
In part 2, subjects will receive C1-INH-R infusion prior to receiving IVIG infusion for three infusions. Complement proteins will be measured pre- and post- infusion. Quality of life and other questionnaires will be administered.
- Conditions
- CVI - Common Variable Immunodeficiency
- Being tested
- C1-esterase inhibitor [recombinant] (C1-INH-R)
- Keywords
- Intravenous Immunoglobulin, C1-esterase inhibitor, Adverse drug reaction (ADR)
- Medical subject headings
- Common Variable Immunodeficiency, Angioedemas, Hereditary, Drug-Related Side Effects and Adverse Reactions
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C1-esterase inhibitor [recombinant] (C1-INH-R)Biological
C1-INH-R is FDA approved and indicated for the treatment of acute attacks of angioedema in adolescent and adult patients with Hereditary Angioedema (HAE) as a replacement for low levels of C1-esterase inhibitor or low function of C1-esterase inhibitor
| Study group | Role | What they receive |
|---|---|---|
| C1-esterase inhibitor [recombinant] (C1-INH-R) | Experimental | Single-site, open-label arm to evaluate the benefit of C1-INH-R in subjects on IVIG therapy who experience ADRs. The study will have 2 periods:
* 6 - 8 weeks - subjects will receive 2 infusions of IVIG
* 9 - 12 weeks - subjects will receive 3 infusions of C1-INH-R prior to IVIG infusion Receives: Biological: C1-esterase inhibitor [recombinant] (C1-INH-R) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The change in Modified Fatigue Severity Scale (mFSS)
Subject-rated Rasch-built 7-item modified fatigue survey scale. Scale rated 0 - 3 (3 = agree, 0 = less agree)
Measured: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
The change in Modified Fatigue Impact Scale (MFIS)
Subject-rated 24 item questionnaire measuring the impact of fatigue rated 0 - 4 (0 = never, 1 = rarely, 2 = sometimes, 3 = often, 4 = almost always)
Measured: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
The change in Migraine Disability Assessment (MIDAS)
Headache severity measurement of number of days affected after infusion
Measured: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
The change in Headache Impact Scale (HIT-6)
Subject-rated measurement of the impact headaches have on the ability to function on the job, at school, at home and in social situations. 6 item questionnaire rated from never (6 points each), rarely (8 points each), sometimes (10 points each), very often (11 points each), always (13 points each). The higher number the more the impact.
Measured: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
The change in Activities of Daily Living Sliding Scale
Subject-rated 10 point scale measuring level of activity with 1 being the worst (least) and 10 being the best (greatest)
Measured: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
The change in Activities of Daily Living Questionnaire
Calculates the number of days missed from work, school/daycare/activities, housework, and regular exercise
Measured: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
The change in Energy Sliding Scale
Subject-rated10 point scale measuring energy level with 1 being the worst (Lowest) and 10 being the best (highest)
Measured: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
The change in Infection Questionnaire
Subject-rated 7 item infection questionnaire measured from 1 to 10 with 1 being the least affected and 10 being the most affected.
Measured: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
The change in Perceived Deficits Questionnaire - cognitive assessment
Subject-rated 20 item questionnaire measuring memory, attention and concentration rated 0 to 4 (0 = never, 1 = rarely, 2 = sometimes, 3 = often, 4 = almost always) with the lower score being least impact.
Measured: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
The change in 36 item short form survey (SF-36)
Health Survey asks 36 questions to measure functional health and well-being from the patient's point of view.
Measured: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
Change in the number of ADRs
Adverse reactions to infusions
Measured: Measured at each infusion (every 3 - 4 weeks)
Secondary outcomes (1)
Change in levels of C1-INH pre- and post-infusion
Laboratory levels of C1-INH total and functional
Measured: Measurement at each infusion (every 3 - 4 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2018
- Study start13 Jun 2018
- Primary completion1 Dec 2019
- Study completion1 Mar 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CVI - Common Variable 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 4
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single Group
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- IMMUNOe Research Centers
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Isaac Melamed, MD, Principal investigator, IMMUNOe Research Centers
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03576469
- Sponsor's protocol ID
- IIS201702-CVID
- Status last verified
- Feb 2021
- First submitted
- 15 Jun 2018
- Last updated
- 15 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Melamed IR, Miranda H, Heffron M, Harper JR. Recombinant Human C1 Esterase Inhibitor for the Management of Adverse Events Related to Intravenous Immunoglobulin Infusion in Patients With Common Variable Immunodeficiency or Polyneuropathy: A Pilot Open-Label Study. Front Immunol. 2021 Mar 2;12:632744. doi: 10.3389/fimmu.2021.632744. eCollection 2021.
PubMed 33737935
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-site, Open-Label, Pilot Study to Evaluate the Benefit of RUCONEST® in Subjects Who Experience ADRs Related to IVIG Infusions
- ClinicalTrials.gov ID
- NCT03576469
- Acronym / sponsor ID
- IIS201702-CVID
- Conditions
- CVI - Common Variable Immunodeficiency
- Keywords
- Intravenous Immunoglobulin, C1-esterase inhibitor, Adverse drug reaction (ADR)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- IMMUNOe Research CentersIndustry (pharma, biotech, devices)
- Study start
- 13 Jun 2018 (actual)
- Primary completion
- 1 Dec 2019 (actual)
- Study completion
- 1 Mar 2020 (actual)
- First posted
- 3 Jul 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients receiving intravenous immunoglobulin (IVIG) therapy for primary immunodeficiency and neurologic conditions may experience adverse drug reactions (ADRs). The mechanism of the ADR is unknown. Currently, the standard practice for these patients is to change from IV to subcutaneous IG (SCIG) but because of the need of immunomodulation or patient preference, SCIG may not be an option. Data has shown that some levels of complement decrease from pre- to post-infusion of IVIG. This study is to determine if replacing this complement protein may ameliorate ADRs.
Detailed description
This is a single-site, pilot study conducted in the US to determine the benefit of human C1-esterase inhibitor [recombinant] (C1-INH-R) therapy to ameliorate ADRs in subjects receiving IVIG therapy experience ADRs post-infusion. Subjects who are currently receiving IVIG for immunodeficiency or neurologic conditions and experience ADRs will be enrolled.
In part 1, subjects will continue to receive IVIG for two infusions. Complement proteins will be measured pre- and post-infusion. Quality of life and other questionnaires will be administered.
In part 2, subjects will receive C1-INH-R infusion prior to receiving IVIG infusion for three infusions. Complement proteins will be measured pre- and post- infusion. Quality of life and other questionnaires will be administered.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single Group
| Arm | Type | Receives |
|---|---|---|
| C1-esterase inhibitor [recombinant] (C1-INH-R) | Experimental | Biological: C1-esterase inhibitor [recombinant] (C1-INH-R)Single-site, open-label arm to evaluate the benefit of C1-INH-R in subjects on IVIG therapy who experience ADRs. The study will have 2 periods: * 6 - 8 weeks - subjects will receive 2 infusions of IVIG * 9 - 12 weeks - subjects will receive 3 infusions of C1-INH-R prior to IVIG infusion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18 years and older experiencing ADRs related to IVIG infusions
- Stable dose of IVIG for 3 months
- Willing to comply with all aspects of the protocol, including blood draws
- Female patients of childbearing potential who are sexually active must be willing to use an acceptable form of contraception. Acceptable forms of contraception are defined as those with a failure rate < 1% when properly applied and include: a combination oral pill, some intra-uterine devices, and a sterilized partner in a stable relationship. Female patients must not be pregnant, planning to become pregnant, or be actively breastfeeding through the entire study period.
Key exclusion criteria (4 listed)
- Receiving treatment for HAE, either prophylactic or acute therapy
- Patients with medical history of allergy to rabbits or rabbit-derived products (including rhC1INH)
- Patients who are pregnant, or breastfeeding, or are currently intending to become pregnant.
- Patients who, in the investigator's opinion, might not be suitable for the trial
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 |
|---|---|---|
| C1-esterase inhibitor [recombinant] (C1-INH-R)C1-INH-R is FDA approved and indicated for the treatment of acute attacks of angioedema in adolescent and adult patients with Hereditary Angioedema (HAE) as a replacement for low levels of C1-esterase inhibitor or low function of C1-esterase inhibitor | Biological | C1-esterase inhibitor [recombinant] (C1-INH-R) |
Primary outcome
The change in Modified Fatigue Severity Scale (mFSS)
Time frame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
Subject-rated Rasch-built 7-item modified fatigue survey scale. Scale rated 0 - 3 (3 = agree, 0 = less agree)
The change in Modified Fatigue Impact Scale (MFIS)
Time frame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
Subject-rated 24 item questionnaire measuring the impact of fatigue rated 0 - 4 (0 = never, 1 = rarely, 2 = sometimes, 3 = often, 4 = almost always)
The change in Migraine Disability Assessment (MIDAS)
Time frame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
Headache severity measurement of number of days affected after infusion
The change in Headache Impact Scale (HIT-6)
Time frame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
Subject-rated measurement of the impact headaches have on the ability to function on the job, at school, at home and in social situations. 6 item questionnaire rated from never (6 points each), rarely (8 points each), sometimes (10 points each), very often (11 points each), always (13 points each). The higher number the more the impact.
The change in Activities of Daily Living Sliding Scale
Time frame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
Subject-rated 10 point scale measuring level of activity with 1 being the worst (least) and 10 being the best (greatest)
The change in Activities of Daily Living Questionnaire
Time frame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
Calculates the number of days missed from work, school/daycare/activities, housework, and regular exercise
The change in Energy Sliding Scale
Time frame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
Subject-rated10 point scale measuring energy level with 1 being the worst (Lowest) and 10 being the best (highest)
The change in Infection Questionnaire
Time frame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
Subject-rated 7 item infection questionnaire measured from 1 to 10 with 1 being the least affected and 10 being the most affected.
The change in Perceived Deficits Questionnaire - cognitive assessment
Time frame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
Subject-rated 20 item questionnaire measuring memory, attention and concentration rated 0 to 4 (0 = never, 1 = rarely, 2 = sometimes, 3 = often, 4 = almost always) with the lower score being least impact.
The change in 36 item short form survey (SF-36)
Time frame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
Health Survey asks 36 questions to measure functional health and well-being from the patient's point of view.
Change in the number of ADRs
Time frame: Measured at each infusion (every 3 - 4 weeks)
Adverse reactions to infusions
1 secondary outcome
Change in levels of C1-INH pre- and post-infusion
Time frame: Measurement at each infusion (every 3 - 4 weeks)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2021.
- Derived from this study: PubMed 33737935Melamed IR, Miranda H, Heffron M, Harper JR. Recombinant Human C1 Esterase Inhibitor for the Management of Adverse Events Related to Intravenous Immunoglobulin Infusion in Patients With Common Variable Immunodeficiency or Polyneuropathy: A Pilot Open-Label Study. Front Immunol. 2021 Mar 2;12:632744. doi: 10.3389/fimmu.2021.632744. eCollection 2021.
- 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.
Isaac Melamed, MD principal investigator
IMMUNOe Research Centers
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing C1-esterase inhibitor [recombinant] (C1-INH-R) in people with CVI - Common Variable Immunodeficiency, run by IMMUNOe Research Centers at 1 site in United States.
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 4 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 15 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The change in Modified Fatigue Severity Scale (mFSS) (time frame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)). The study lists 11 primary outcomes in all. 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 NCT03576469, 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 15 Feb 2021.