Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases.

Brief Title

Efficacy, Safety and Pharmacokinetics of Gammaplex in Primary Immunodeficiency Diseases.

Official Title

A Phase III, Multicenter, Open-Label Study To Evaluate The Efficacy, Safety, and Pharmacokinetics of Gammaplex® in Primary Immunodeficiency Diseases

Brief Summary

      The main objective of this study is to see if GAMMAPLEX is efficacious with respect to Food
      and Drug Administration (FDA) minimal requirements (no more than 1 serious, acute, bacterial
      infection per subject per year) in subjects with Primary Immunodeficiency Diseases (PID). The
      secondary objectives are to assess the safety and tolerability of GAMMAPLEX and to determine
      if GAMMAPLEX has a pharmacokinetic (PK) profile comparable with that of intact Immunoglobulin
      G (IgG) in subjects with PID.
    

Detailed Description

      Primary Efficacy Variable The primary variable is the number of serious, acute, bacterial
      infections/subject/year, and it will be based on the total of all of the following events as
      defined by the FDA: bacterial Pneumonia, bacteremia/sepsis, osteomyelitis/septic arthritis,
      visceral abscess, and bacterial meningitis.

      Secondary Efficacy Variables Secondary efficacy will be determined by using the following
      variables: number of days of work/school missed because of infection per subject year; number
      and days of hospitalizations because of infection per subject year; number of visits to
      physicians for acute problems and/or number of visits to hospital emergency rooms per subject
      year; other infections documented by fever or a positive result on a radiograph and/or
      culture; number of infectious episodes per subject per year; number of days on therapeutic
      antibiotics.These data will be entered into the subject diary, confirmed by the physician,
      and entered on the electronic-CRF (e-CRF).

      Safety Variables. The variables used to assess safety will be the following: adverse events
      (AEs); vital signs; clinical laboratory tests and Direct Coombs' Test; transmission of
      viruses; physical examination.

      Test product, dose/mode of administration, batch number(s): The GAMMAPLEX dose is 300-800
      mg/kg/infusion (milligram per killgram per infusion) every 21 or 28 days, intravenously. At
      least 2 batches will be used in this study and no more than 1 batch in any given infusion.

      Duration of treatment:

      The total duration of treatment is 12 months.
    

Study Phase

Phase 3

Study Type

Interventional


Primary Outcome

Number of Serious, Acute, Bacterial Infections (SABIs) Per Subject Per Year in Subjects With Primary Immunodeficiency Disease.

Secondary Outcome

 The Pharmacokinetic (PK) Half-Life of Immunoglobulin G (IgG)

Condition

Primary Immunodeficiency

Intervention

Gammaplex (Intravenous immunoglobulin)

Study Arms / Comparison Groups

 Gammaplex
Description:  Gammaplex

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

50

Start Date

January 2006

Completion Date

November 2007

Primary Completion Date

November 2007

Eligibility Criteria

        Inclusion Criteria:

          -  1. The subject is 3 years of age or older, of either sex, belonging to any ethnic
             group, and above a minimum weight of 27.5 kg. This weight is based on the amount of
             blood required for testing. If subject is participating in the PK segment, the minimum
             weight required is 37 kg.

             2. The subject has a primary immunodeficiency disease, which has as a significant
             component of hypogammaglobulinemia and/or antibody deficiency (e.g. (exempli gratia /
             for example), common variable immunodeficiency, X-linked and autosomal forms of
             agammaglobulinemia, hyper-immunoglobulin M (hyper-IgM) syndrome, Wiskott-Aldrich
             Syndrome). Isolated deficiency of a single IgG subclass, or of specific antibodies
             without hypogammaglobulinemia per se, does not qualify for inclusion.

             3. The subject has been receiving licensed or investigational (Phase III or IIIb)
             immunoglobulin intravenous (IGIV) replacement therapy at a dose that has not changed
             by + 50% of the mean dose for at least 3 months before study entry and is between 300
             and 800 mg/kg/infusion. The infusion interval must be between 21 and 28 days
             inclusive. The subject must have maintained a trough level at least 300 mg/dL
             (milligram per decilitre) above baseline serum IgG levels (defined as before
             initiation of any gamma globulin treatment for that subject). The trough level must be
             600 mg/dL.

             4. Trough levels of IgG and dose of IGIV, treatment intervals, and the trade name of
             the IGIV treatments used for the last 2 consecutive routine (licensed or
             investigational product) must be documented for each subject before the first infusion
             in this study can be administered.

             5. If a subject is a female of child-bearing potential, she must have a negative
             result on an Human Chorionic Gonadotrophin (HCG)-based pregnancy test.

             6. If a subject is a female who is or becomes sexually active, she must practice
             contraception by using a method of proven reliability for the duration of the study.

             7. The subject is willing to comply with all aspects of the protocol, including blood
             sampling, for the duration of the study.

             8. The subject has signed an informed consent form (if at least 18 years old) or the
             subject's parent or legal guardian has signed the informed consent form. If
             appropriate, the subject has signed a child assent form (See Section 12.3).

        Exclusion Criteria:

          -  Subjects will be excluded if any of the following exclusion criteria are met:

               1. The subject has a history of any severe anaphylactic reaction to blood or any
                  blood-derived product.

               2. The subject is known to be intolerant to any component of GAMMAPLEX, such as
                  sorbitol (i.e.(id est / that is) , intolerance to fructose).

               3. The subject has selective immunoglobulin A (IgA) deficiency, history of reaction
                  to products containing IgA, or has a history of antibodies to IgA.

               4. Subjects who have completed the study and subjects who have withdrawn cannot
                  participate in the study for a second time.

               5. The subject is currently receiving, or has received, any investigational agent,
                  other than an immune serum globulin (ISG) preparation that is being evaluated in
                  a Phase III or IIIb study, within the prior 3 months.

               6. The subject has been exposed to blood or any blood product or derivative within
                  the last 6 months, other than a commercially available IGIV or other forms of
                  commercially available and licensed ISG or an ISG product that is in Phase III or
                  IIIb studies.

               7. The subject is pregnant or is nursing.

               8. The subject is positive for any of the following at screening:

                    -  Serological test for Human immunodeficiency virus (HIV) 1&2, Hepatitis C
                       virus (HCV), or Hepatitis B surface antigen (HBsAg)

                    -  Nucleic Acid test (NAT) for HCV

                    -  NAT for HIV

               9. The subject, at screening, has levels greater than 2.5 times the upper limit of
                  normal as defined at the central laboratory of any of the following:

                    -  Alanine transaminase (ALT)

                    -  Aspartate transaminase (AST)

              10. The subject has a severe renal impairment (defined as serum creatinine greater
                  than 2 times the upper limit of normal or Blood urea nitrogen (BUN) greater than
                  2.5 times the upper limit of normal for the range of the laboratory doing the
                  analysis); the subject is on dialysis; the subject has a history of acute renal
                  failure.

              11. The subject is known to abuse alcohol, opiates, psychotropic agents, or other
                  chemicals or drugs, or has done so within the past 12 months.

              12. The subject has a history of deep vein thrombosis (DVT), or thrombotic
                  complications of IGIV therapy.

              13. The subject suffers from any acute or chronic medical condition (e.g., renal
                  disease or predisposing conditions for renal disease, coronary artery disease, or
                  protein losing state) that, in the opinion of the investigator, may interfere
                  with the conduct of the study.

              14. The subject has an acquired medical condition, such as chronic lymphocytic
                  leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (Absolute
                  neutrophil count (ANC) < 1000 x 109/L).

              15. The subject is receiving the following medication:

                    -  Immunosuppressive drugs

                    -  The subject is receiving the following medication: Steroids (long-term
                       daily, >0.15 mg /kg/day of prednisone or prednisolone of equivalent dose of
                       other corticosteroids) The requirement for burst or intermittent courses
                       would not exclude the subject.

                    -  Immunomodulatory drugs

              16. The subject has non-controlled arterial hypertension (systolic blood pressure >
                  160 mmHg (millimeters of mercury) and/or diastolic blood pressure > 100 mmHg).

              17. The subject has anemia (hemoglobin < 10 g/dL) at screening.
      

Gender

All

Ages

3 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Melvin Berger, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00278954

Organization ID

GMX01


Responsible Party

Sponsor

Study Sponsor

Bio Products Laboratory


Study Sponsor

Melvin Berger, MD, Principal Investigator, Rainbow Babies & Children's Hospital, Cleveland, Ohio


Verification Date

January 2013