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

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.

Study Overview

• Status: Completed
• Conditions: CVI - Common Variable Immunodeficiency
• Intervention / Treatment: Biological: C1-esterase inhibitor [recombinant] (C1-INH-R)

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 Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Centennial, Colorado, United States, 80112
      • IMMUNOe Research Centers

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Biological: 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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: IMMUNOe Research Centers

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 13, 2018
• Primary Completion (Actual): December 1, 2019
• Study Completion (Actual): March 1, 2020

Study Registration Dates

• First Submitted: June 15, 2018
• First Submitted That Met QC Criteria: July 2, 2018
• First Posted (Actual): July 3, 2018

Study Record Updates

• Last Update Posted (Actual): February 15, 2021
• Last Update Submitted That Met QC Criteria: February 11, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Intravenous Immunoglobulin; C1-esterase inhibitor; Adverse drug reaction (ADR)
• Additional Relevant MeSH Terms: Immunologic Deficiency Syndromes; Immune System Diseases; Common Variable Immunodeficiency; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Complement Inactivating Agents; Complement C1 Inhibitor Protein; Complement C1 Inactivator Proteins; Complement C1s
• Other Study ID Numbers: IIS201702-CVID

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No