Clinical trial NCT03576469: A Study to Evaluate the Benefit of RUCONEST® in Subjects Who Experience ADRs Related to IVIG Infusions
Official title: A Single-site, Open-Label, Pilot Study to Evaluate the Benefit of RUCONEST® in Subjects Who Experience ADRs Related to IVIG Infusions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: CVI - Common Variable Immunodeficiency
Keywords: Intravenous Immunoglobulin
C1-esterase inhibitor
Adverse drug reaction (ADR)
Lead sponsor: IMMUNOe Research Centers
Sponsor class: INDUSTRY
First posted: 2018-07-03
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group
Primary purpose: PREVENTION

Brief 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. 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.

Eligibility criteria: 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

Primary outcomes:
measure: The change in Modified Fatigue Severity Scale (mFSS)
timeFrame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
measure: The change in Modified Fatigue Impact Scale (MFIS)
timeFrame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
measure: The change in Migraine Disability Assessment (MIDAS)
timeFrame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
measure: The change in Headache Impact Scale (HIT-6)
timeFrame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
measure: The change in Activities of Daily Living Sliding Scale
timeFrame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
measure: The change in Activities of Daily Living Questionnaire
timeFrame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
measure: The change in Energy Sliding Scale
timeFrame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
measure: The change in Infection Questionnaire
timeFrame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
measure: The change in Perceived Deficits Questionnaire - cognitive assessment
timeFrame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
measure: The change in 36 item short form survey (SF-36)
timeFrame: Measurement prior to infusion 3 (week 9 - 12) compared to end of study (week 19 - 25)
measure: Change in the number of ADRs
timeFrame: Measured at each infusion (every 3 - 4 weeks)
Secondary outcomes:
measure: Change in levels of C1-INH pre- and post-infusion
timeFrame: Measurement at each infusion (every 3 - 4 weeks)
Other outcomes:
Locations:
city: Centennial
country: United States
facility: IMMUNOe Research Centers
state: Colorado
Study officials:
affiliation: IMMUNOe Research Centers
name: Isaac Melamed, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.