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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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:
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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 |
| 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 |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Isaac Melamed, MD | IMMUNOe Research Centers | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| IMMUNOe Research Centers | Centennial | Colorado | 80112 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33737935 | Derived | 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. |
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| ID | Term |
|---|---|
| D017074 | Common Variable Immunodeficiency |
| D054179 | Angioedemas, Hereditary |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| ID | Term |
|---|---|
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D000799 | Angioedema |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D050718 | Complement C1 Inhibitor Protein |
| ID | Term |
|---|---|
| D006023 | Glycoproteins |
| D006001 | Glycoconjugates |
| D002241 | Carbohydrates |
| D003174 | Complement C1 Inactivator Proteins |
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Single Group
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|
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) |
| D002318 |
| Cardiovascular Diseases |
| D000081208 | Hereditary Complement Deficiency Diseases |
| D000081207 | Primary Immunodeficiency Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D064419 | Chemically-Induced Disorders |
| D015843 |
| Serpins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D003169 | Complement Inactivator Proteins |
| D003165 | Complement System Proteins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |