This is a clinical study to evaluate efficacy, pharmacokinetic and safety of human with normal immunoglobulin for intravenous administration in patients with primary immunodeficiency diseases.

Phase 3

Not yet recruiting

• Conditions: Immunodeficiency, unspecified,

• Registration Number: CTRI/2022/12/048138
• Lead Sponsor: Intas Pharmaceutical Ltd India

Brief Summary

This is a prospective, Non-randomized, Open Label, Single Arm, Multicentric, Phase III clinical study to evaluate efficacy, pharmacokinetic and safety of human normal immunoglobulin for IV administration in patients with primary immunodeficiency diseases.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-12-23
• Last Update Posted: 2023-04-11

Recruitment & Eligibility

• Status: Not Yet Recruiting
• Sex: All
• Target Recruitment: 89

Inclusion Criteria

• Participants are eligible to be included in the study only if all of the following criteria apply- 1 Participant or their legally acceptable representative must sign ICF indicating that he or she understands the purpose of, procedures and restriction required for the study Parent(s) (preferably both if available or as per local requirements) must sign an ICF indicating that he or she understands the purpose of, and procedures required for, the study and is willing to allow the child to participate in the study.2 Participant must be 2 to 65 years of age (both inclusive) at the time of providing the informed consent.3 Participants with documented clinical diagnosis of a primary immunodeficiency disease as defined by IUIS (International Union of Immunological Societies) and require treatment with IVIg. Confirmation of PID diagnosis may include a review of infection history, serum IgG concentration at diagnosis and prior to immunoglobulin therapy and responses (failure to achieve two fold rise in IgG antibody titre) to vaccination with polysaccharide and protein vaccines.4 Participants with documented agammaglobulinemia (defined as the total absence of one or more classes of antibodies) or hypogammaglobulinemia (defined as low levels of one or more classes [that is at least 2 standard deviations under the mean level per age) including but not limited to the following: humoral-based immunodeficiency syndromes (e.g., X-linked agammaglobulinemia, common variable immunodeficiency), and combined immunodeficiency syndromes without lymphocytopenia (e.g., hyper-immunoglobulin M [IgM] immunodeficiency syndrome) • Newly diagnosed participants- who are eligible to receive IVIg treatment as per the investigator discretion.• Participants already on IVIg treatment− Participants must be receiving IVIg treatment for primary immunodeficiency − Participant must be receiving stable dose of an approved IVIg within 200-900 mg/kg (± 20% of the mean dose for the last 3 infusions) with established treatment intervals of 21- or 28-day (±3 days or ±4 days, respectively) for at least 3 infusion cycles (one of which could be the screening visit result).− At least 2 documented IgG trough levels while receiving an IVIg, of more than or equal to 450 mg/dL obtained at 2 infusion cycles within 12 months (1 must be within 6months) prior to enrollment.5 Participants who are otherwise medically stable on the basis of physical examination, medical history and vital signs, chest x-ray and 12-lead ECG performed at screening.
• Any abnormalities must be consistent with the underlying illness in the study population and this determination must be recorded in the participant source documents and initialed by the investigator.6 Participants who are otherwise medically stable on the basis of clinical laboratory tests performed at screening.
• If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study.
• This determination must be recorded in the participant source documents and initialed by the investigator.7 A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:• Is not a woman of childbearing potential (WOCBP) OR• Is a WOCBP and using an acceptable contraceptive method during the intervention period.
• The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.• A WOCBP must have a negative highly sensitive serum pregnancy test at screening and negative urine pregnancy test before IMP administration.• Additional requirements for pregnancy testing after study intervention are located in Appendix 10.2.• The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy.
• A female participant must provide assurance to follow precautions to avoid pregnancy during the study period.8 Male participants are eligible to participate if they agree to the following during the intervention period and for at least 6 months after the last dose of study intervention:• Must agree not to donate sperm for the purpose of reproduction PLUS EITHER• Be abstinent from heterosexual [or homosexual] intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR• Must agree to use contraception /barrier as detailed below:− A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person − Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant.10 Participants must be willing and able to adhere to protocol requirements.

Exclusion Criteria

• Any potential participant who meets any of the following criteria will be excluded from participating in the study:1 History of clinically significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, psychiatric, or metabolic disturbances.
• 2 Known allergies, hypersensitivity, or persistent reactions (urticaria, breathing difficulty, severe hypotension, or anaphylaxis) following human normal immunoglobulin intravenous or its excipients or following plasma-derived products (refer to the prescribing information of study intervention) OR known history of anaphylactic reactions to IgA found in other products.3 Exposure to blood or any blood product or derivative, other than commercially available human IVIg or human albumin within the past 3 months.4 Participant has known Selective Immunoglobulin A (IgA) Deficiency (with or without antibodies to IgA).
• (Note: exclusion is for the specific diagnostic entity.
• It does not exclude other forms of humoral primary immunodeficiency which have decreased IgA in addition to decreased IgG requiring immune globulin [IgG] replacement).
• 5 Participant with an acquired medical condition that is known to cause secondary immune deficiency, such as chronic lymphocytic leukemia, lymphoma, multiple myeloma, chronic or recurrent neutropenia (ANC less than 1000 cells/mm3), or human immunodeficiency virus (HIV) infection/acquired immune deficiency syndrome (AIDS).6 Participant having contraindication for intravenous immunoglobulin or has been diagnosed with dysgammaglobulinemia, isolated IgG subclass deficiency, isolated specific antibody deficiency disorder, or transien hypogammaglobulinemia of infancy.7 History of autoimmune hemolytic anemia.8 History of congenital impairment of pulmonary function.
• 9 The participant currently has a known hyperviscosity syndrome.10 Participant has a predisposition for acute renal failure (e.g. any degree of pre-existing renal insufficiency or routine treatment with known nephritic drugs) and/or has a history of acute renal failure; and/or is on dialysis.11 Participant has total protein >9 g/dL and/or participants with myeloma, macroglobulinemia (IgM) and paraproteinemia.
• 12 Participant (if less than 18 years of age) has non-controlled hypertension at a level of greater than or equal to the 90th percentile blood pressure (either systolic or diastolic) for their age and height or the adult participant has non-controlled arterial hypertension (systolic blood pressure more than or equal to 160 mmHg and/or diastolic blood pressure more than or equal to 100 mmHg).13 Participant has a known history, or is positive at enrollment, for human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus.14 Participant with documented history of bleeding disorders or who are on anti-coagulation therapy.15 Participant has an active viral or bacterial infection or symptoms/signs consistent with such an infection (as documented by culture or diagnostic imaging and (or) a body temperature exceeding 38.5°C (101.3°F)), excluding chronic sinusitis or bronchiectasis, within the two weeks prior to the initial dose of investigational product.
• Participants may be receiving antibiotics as long as signs/symptoms of infection have been absent for two weeks prior to the initial infusion of IP.Note: If an viral or bacterial infection occurs during the screening period and prior to the first dose of study intervention, the participant will be a Screen Failure.16 The participant is receiving any of the following medications: (a) immunosuppressants including chemotherapeutic agents; (b) immunomodulators; (c) long-term systemic corticosteroids defined as daily dose more than or equal to 0.15 mg of prednisone equivalent/kg/day for more than 10 days.Note: Intermittent courses of corticosteroids of not more than 10 days would not exclude a participant.
• Inhaled or topical corticosteroids may be allowed at discretion of the investigator.17 Participant has a lifetime history of at least one thrombotic event including deep vein thrombosis, cerebrovascular accident, pulmonary embolism, transient ischemic attacks, unstable or advanced ischemic heart disease or myocardial infarction.18 Participant has significant protein losing enteropathy, nephrotic syndrome, or lymphangiectasia.19 History of Lymphoma, leukemia, or any malignancy except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 5 years; carcinoma in situ of the cervix; or malignancy, which is considered cured with minimal risk of recurrence.
• NOTE: Participants with planned surgical procedures to be conducted under local anesthesia may participate.
• However, the same needs to be documented in the patient case-record files and will not be considered as serious adverse event.
• 22 Prior to screening, participants received an investigational intervention or used an invasive investigational medical device within 30 days or 5 half-lives, whichever is longer, or has received any investigational blood product, with the exception of other IgG products, within the previous 3 months before signing informed consent.23 Congestive heart failure (New York Heart Association III/IV), cardiomyopathy, cardiac arrhythmia associated with thromboembolic events (e.g., atrial fibrillation), or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant safety or that could prevent, limit, or confound the protocol-specified assessments.24 Participant with any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To evaluate the efficacy of human normal immunoglobulin	Per person per year.
bacterial infection (SBI) compared with historical control data in participants with primary immunodeficiency disease.	Per person per year.
intravenous preventing serious	Per person per year.

Secondary Outcome Measures

Name	Time	Method
To evaluate pharmacokinetics of human normal immunoglobulin	intravenous infusion in

Trial Locations

Locations (9)

AIIMS; 🇮🇳 Khordha, ORISSA, India

Aster- CMI Hospital; 🇮🇳 Bangalore, KARNATAKA, India

Bai Jerbai Wadia Hospital for Children; 🇮🇳 Mumbai, MAHARASHTRA, India

Indira Gandhi Institute of child Health, Bangalore; 🇮🇳 Bangalore, KARNATAKA, India

Nizams Institute Of Medical Sciences; 🇮🇳 Hyderabad, TELANGANA, India

Post Graduate Institute of Child Health; 🇮🇳 Nagar, UTTAR PRADESH, India

Radiance Hospital; 🇮🇳 Ahmadabad, GUJARAT, India

Sanjay Gandhi Postgraduate Institute of Medical Sciencies; 🇮🇳 Lucknow, UTTAR PRADESH, India

Sir HN Reliance Foundation & Research Centre; 🇮🇳 Mumbai, MAHARASHTRA, India

AIIMS

🇮🇳Khordha, ORISSA, India

Dr Samarendra Mahapatro

Principal investigator

9438884180

samarendramahapatro@yahoo.com