A Study of HyQvia and Gammagard Liquid (Kiovig) in Adults With Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP)

Baxalta

Status and phase: Completed; Phase 3

Conditions: Chronic Inflammatory Demyelinating Polyradiculoneuropathy

Treatments: Biological: HYQVIA; Biological: IGIV GAMMAGARD LIQUID/KIOVIG; Biological: 0.25% albumin placebo solution with rHuPH20; Biological: IGIV GAMUNEX®-C

Study type: Interventional

Funder types: Industry

Identifiers

NCT02549170

2014-005496-87 (EudraCT Number)

161403

Details and patient eligibility

About

The aim of this study is to learn more about the following treatment options in adults with CIDP:

• Subcutaneous self-infusion with HyQvia.
• Intravenous infusion with Gammagard/Kiovig. Gammagard and Kiovig are the brand names for the same immunoglobulin compound.

The study is in two parts. In Part 1, participants receive either HyQvia or a placebo subcutaneously. In Part 2 (only for participants who have a CIPD relapse during Part 1), participants will receive Gammagard Liquid/Kiovig intravenously. US participants will receive Gamunex-C.

The first SC infusion will be given in the study clinic. The remaining SC infusions may be given in the study clinic or the participant's home. This will be decided by the study doctor and whether the participant or their caregiver can do the self-infusion.

Enrollment: 138 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Males or females of age greater than or equal to (>=)18 years old at the time of screening.

2. Participant has a documented diagnosis of definite or probable Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) (focal atypical CIDP and pure sensory atypical CIDP will be excluded), as confirmed by a neurologist specializing/experienced in neuromuscular diseases to be consistent with the European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) 2010 criteria (European Federation of Neurological Societies, 2010). Fulfillment of electrodiagnostic criteria must be confirmed by an independent qualified/experienced central reader.

3. Participant has responded to IgG treatment in the past (partial or complete resolution of neurological symptoms and deficits), and must currently be on stable doses of IGIV treatment within the dose range equivalent to a cumulative monthly dose of 0.4 to 2.4 gram per kilogram (g/kg) BW (inclusive) administered intravenously for at least 12 weeks prior to screening. The dosing interval of IGIV treatment must be between 2 and 6 weeks (inclusive). Variations in the dosing interval of up to ± 7 days or monthly dose amount of up to ± 20% between participant's pre-study Immunoglobulin G (IgG) infusions are within acceptable limits.

4. INCAT disability score between 0 and 7 (inclusive). Participants with INCAT scores of 0, 1 (whether from upper or lower extremities), or 2 (if at least 1 point is from an upper extremity) at screening and/or baseline will be required to have a history of significant disability as defined by an INCAT disability score of 2 (must be exclusively from the lower extremities) or greater documented in the medical record. Participants will be eligible if one of the below eligibility criteria are met:

   Screening and Baseline INCAT disability score of between 3 and 7 inclusive.

   1. Screening and/or Baseline INCAT disability score of 2 (both points are from lower extremities).
   2. Screening and/or Baseline INCAT disability score of 2 (both points are not from lower extremities) AND has at least a score of 2 or greater documented in the medical record prior to screening. If a score was greater than 2 documented in the medical record prior to screening at least 2 points must be from lower extremities.
   3. Screening and/or Baseline INCAT disability score of 0 or 1 AND has at least a score of 2 or greater (both from lower extremities) documented in the medical record prior to screening, at least 2 points must be from lower extremities.

5. If female of childbearing potential, the participant must have a negative pregnancy test at screening and agree to employ a highly effective contraceptive measure throughout the course of the study and for at least 30 days after the last administration of investigational product (IP).

6. Participant is willing and able to sign an Informed Consent Form (ICF).

7. Participant is willing and able to comply with the requirements of the protocol.

Exclusion criteria

1. Participants with Focal atypical CIDP or pure sensory atypical CIDP.

2. Any neuropathy of other causes, including:

   1. Hereditary demyelinating neuropathies, such as hereditary sensory and motor neuropathy (HSMN) (Charcot-Marie-Tooth [CMT] disease), and hereditary sensory and autonomic neuropathies (HSANs).
   2. Neuropathies secondary to infections, disorders, or systemic diseases such as Borrelia burgdorferi infection (Lyme disease), diphtheria, systemic lupus erythematosus, POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome, osteosclerotic myeloma, diabetic and non-diabetic lumbosacral radiculoplexus neuropathy, lymphoma, and amyloidosis.
   3. Multifocal acquired demyelinating sensory and motor neuropathy (MADSAM).
   4. Multifocal motor neuropathy (MMN).
   5. Drug-, biologic-, chemotherapy-, or toxin-induced peripheral neuropathy.

3. Immunoglobulin M (IgM) paraproteinemia, including IgM monoclonal gammopathy with high titer antibodies to myelin-associated glycoprotein.

4. Prominent sphincter disturbance.

5. Central demyelinating disorders (eg, multiple sclerosis).

6. Any chronic or debilitating disease, or central nervous disorder that causes neurological symptoms or may interfere with assessment of CIDP or outcome measures (eg, arthritis, stroke, Parkinson's disease, and diabetic peripheral neuropathy) (Participants with clinically diagnosed diabetes mellitus who do not have diabetic peripheral neuropathy, who have adequate glycemic control with Hemoglobin A1C; also known as glycosylated or glycated hemoglobin (HbA1C) of less than (<) 7.5% at screening, and who agree to maintain adequate glycemic control during the study are allowed).

7. Congestive heart failure (New York Heart Association [NYHA] Class III/IV), unstable angina, unstable cardiac arrhythmias, or uncontrolled hypertension (ie, diastolic blood pressure greater than (>) 100 millimeter of mercury (mmHg) and/or systolic blood pressure >160 mmHg).

8. History of deep vein thrombosis or thromboembolic events (eg, cerebrovascular accident, pulmonary embolism) in the past 12 months.

9. Condition(s) which could alter protein catabolism and/or IgG utilization (eg, protein-losing enteropathies, nephrotic syndrome).

10. Known history of chronic kidney disease, or glomerular filtration rate (GFR) of <60 milliliter per minute per 1.73 square meter (mL/min/1.73m^2) estimated based on CKD-EPI equation (Levey et al., 2009) at the time of screening.

11. Participant with active malignancy requiring chemotherapy and/or radiotherapy, or history of malignancy with less than 2 years of complete remission prior to screening. Exceptions are: adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, and stable prostate cancer not requiring treatment.

12. Clinically significant anemia or hemoglobin (Hgb) level of less than (<) 10.0 grams per deciliter (g/dL) at screening.

13. Hypersensitivity or adverse reactions (AR's) (eg, urticaria, breathing difficulty, severe hypotension, or anaphylaxis) to human blood products such as human IgG, albumin, or other blood components.

14. Known allergy to hyaluronidase of human (including recombinant human hyaluronidase) or animal origin (such as bee or wasp venom).

15. Known history of or immunoglobulin A (IgA) deficiency (<8 milligram per deciliter [mg/dL]) at screening.

16. Abnormal laboratory values at screening:

    1. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) > 2.5* upper limit of normal (ULN)
    2. Platelet count <100,000 cells per microliter (cells/mcL).
    3. Absolute neutrophil count (ANC) <1000 cells/mcL.

17. Ongoing/active infection with hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) Type 1/2 infection.

18. The participant has received or is currently receiving treatment with immunomodulatory/ immunosuppressive agents within 6 months prior to screening.

19. Participant has received or is currently receiving treatment with corticosteroids dose within 8 weeks prior to screening, regardless of indication.

20. Participant has undergone plasma exchange (PE) within 3 months prior to screening.

21. The participant has any disorder or condition that in the investigator's judgment may impede the participant's participation in the study, pose increased risk to the participant, or confound the results of the study.

22. The participant is nursing or intends to begin nursing during the course of the study.

23. Participant has participated in another clinical study involving an IP or investigational device within 30 days prior to enrollment, or is scheduled to participate in another clinical study (with the exception of the HYQVIA/HyQvia extension study in CIDP) involving an IP or investigational device during the course of this study.

24. The participant is a family member or employee of the investigator.

25. Participants with acquired or inherited thrombophilic disorders. These will include the specific types of acquired or inherited thrombophilic disorders that could put participants at risk of develop thrombotic events. Examples include:

    a. Hereditary Thrombophilias i. Factor V Leiden mutation. ii. Prothrombin 20210A mutation. iii. Protein C deficiency. iv. Protein S deficiency. v. Antithrombin deficiency. b. Acquired thrombophilias i. Antiphospholipid antibody syndrome. ii. Activated protein C Resistance acquired. iii. Homocystinemia.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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138 participants in 5 patient groups, including a placebo group

Epoch 1: HYQVIA/HyQvia

Experimental group

Description:

Participants received HYQVIA/HyQvia (rHuPH20) 80 U/g IG, following by SC injection of immunoglobulin (IGI) 10% at the same monthly equivalent IG dose as the individual participant's pre-randomized IG dose when administered every 2, 3, or 4 weeks for 30.28 weeks or until relapse.

Treatment:

Biological: HYQVIA

Epoch 1: Placebo with rHuPH20

Placebo Comparator group

Description:

Participants received rHuPH20 80 U/I0 mL placebo solution, followed by SC placebo infusion at matching infusion volume as the participant's pre-randomization monthly equivalent IG dose when administered every 2, 3, or 4 weeks for 31.54 weeks or until relapse.

Treatment:

Biological: 0.25% albumin placebo solution with rHuPH20

Epoch 2: E1: Placebo Relapse - E2: GGL/KIOVIG

Experimental group

Description:

Participants who were enrolled to receive placebo with rHuPH20 and achieved chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) relapse during Epoch 1 received the induction dose of GGL/KIOVIG 2 g/kg bi-weekly (BW), followed by IV infusion at the same monthly equivalent dose as the participant's pre-randomization IGIV dosing regimen when administered every 3 weeks for 25.63 weeks or until relapse.

Treatment:

Biological: IGIV GAMMAGARD LIQUID/KIOVIG

Epoch 2: E1: HYQVIA Relapse - E2: GGL/KIOVIG

Experimental group

Description:

Participants who were enrolled to receive HYQVIA/HyQvia (rHuPH20) and achieved CIDP relapse during Epoch 1 received the induction dose of GGL/KIOVIG 2 g/kg BW, followed by IV infusion at the same monthly equivalent dose as the participant's pre-randomization IGIV dosing regimen when administered every 3 weeks for 28.67 weeks or until relapse.

Treatment:

Biological: IGIV GAMMAGARD LIQUID/KIOVIG

Epoch 2: E1: Placebo Relapse - E2: GAMMUNEX-C

Experimental group

Description:

Participants who were enrolled to receive placebo with rHuPH20 and achieved CIDP relapse during Epoch 1 received the induction dose of GAMMUNEX-C 2 g/kg BW, followed by IV infusion at the same monthly equivalent dose as the participant's pre-randomization IGIV dosing regimen when administered every 3 weeks for 24.33 weeks or until relapse.

Treatment:

Biological: IGIV GAMUNEX®-C