A Study to Evaluate the Benefit of RUCONEST® in Subjects Who Experience ADRs Related to IVIG Infusions

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Single-site, Open-Label, Pilot Study to Evaluate the Benefit of RUCONEST® in Subjects Who Experience ADRs Related to IVIG Infusions

Conditions
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CVI - Common Variable Immunodeficiency

Intervention / Treatment
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* Biological: C1-esterase inhibitor [recombinant] (C1-INH-R)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: C1-esterase inhibitor [recombinant] (C1-INH-R)<br>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 | Biological: C1-esterase inhibitor [recombinant] (C1-INH-R)<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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) | 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) | 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 | 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. | 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) | 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 | 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) | 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. | 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. | 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. | 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 at each infusion (every 3 - 4 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in levels of C1-INH pre- and post-infusion | Laboratory levels of C1-INH total and functional | Measurement at each infusion (every 3 - 4 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intravenous Immunoglobulin, C1-esterase inhibitor, Adverse drug reaction (ADR)