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

NCT03576469 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: IIS201702-CVID
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

CVI - Common Variable Immunodeficiency

Keywords

Intravenous Immunoglobulin; C1-esterase inhibitor; Adverse drug reaction (ADR)

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (1)

• Change in levels of C1-INH pre- and post-infusion

  Measurement at each infusion (every 3 - 4 weeks)

Study Arms (1)

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

Biological: C1-esterase inhibitor [recombinant] (C1-INH-R)

Interventions

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

C1-esterase inhibitor [recombinant] (C1-INH-R)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• IMMUNOe Research Centers: lead

Study Sites (1)

IMMUNOe Research Centers

Centennial, Colorado, 80112, United States

Location

Related Publications (1)

• 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.

  PMID: 33737935 DERIVED

MeSH Terms

Conditions

Common Variable Immunodeficiency; Angioedemas, Hereditary; Drug-Related Side Effects and Adverse Reactions

Interventions

Complement C1 Inhibitor Protein

Condition Hierarchy (Ancestors)

Immunologic Deficiency Syndromes; Immune System Diseases; Angioedema; Vascular Diseases; Cardiovascular Diseases; Hereditary Complement Deficiency Diseases; Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Urticaria; Skin Diseases, Vascular; Skin Diseases; Skin and Connective Tissue Diseases; Hypersensitivity, Immediate; Hypersensitivity; Chemically-Induced Disorders

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Complement C1 Inactivator Proteins; Serpins; Peptides; Amino Acids, Peptides, and Proteins; Complement Inactivator Proteins; Complement System Proteins; Immunoproteins; Blood Proteins; Proteins

Study Officials

• Isaac Melamed, MD

  IMMUNOe Research Centers

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single Group

Study Record Dates

• First Submitted: June 15, 2018
• First Posted: July 3, 2018
• Study Start: June 13, 2018
• Primary Completion: December 1, 2019
• Study Completion: March 1, 2020
• Last Updated: February 15, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)