CTRI/2022/12/048138 [Registered on: 15/12/2022] Trial Registered Prospectively
Last Modified On:
04/11/2023
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Biological
Study Design
Other
Public Title of Study
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.
Scientific Title of Study
A Prospective, Nonrandomized, Open label, Single Arm, Multicentric, Phase
III Clinical Study To Evaluate Efficacy, Pharmacokinetics And Safety of Human Normal Immunoglobulin For Intravenous Administration In Patients With Primary Immunodeficiency Diseases
Trial Acronym
Secondary IDs if Any
Secondary ID
Identifier
0121-22, Version: 1.0, Date: 11 April 2022
Protocol Number
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Prashant Modi
Designation
Associate Vice President
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda House, Plot No. 38, Survey no. 388,Near Silver Oak Club,S. G. Highway, Gota
Ahmadabad GUJARAT 382481 India
Phone
07940202214
Fax
07940202021
Email
prashantmodi@lambda-cro.com
Details of Contact Person Scientific Query
Name
Dr Naman Shah
Designation
Sr. General Manager
Affiliation
Lambda Therapeutic Research Ltd.
Address
Lambda house, Plot No. 38, Survey no. 388, Near Silver Oak Club,S. G. Highway, Gota
Ahmadabad GUJARAT 382481 India
Phone
07940202214
Fax
07940202021
Email
namanshah@lambda-cro.com
Details of Contact Person Public Query
Name
Prashant Modi
Designation
Associate Vice President
Affiliation
Lambda Therapeutic Research Ltd
Address
Lambda House, Plot No. 38, Survey no. 388,Near Silver Oak Club,S. G. Highway, Gota
Ahmadabad GUJARAT 382481 India
Phone
07940202214
Fax
07940202021
Email
prashantmodi@lambda-cro.com
Source of Monetary or Material Support
Intas Pharmaceutical Ltd., India
Intas Plasma
Fractionation Unit, Plot No. 496/1/A&B, Sarkhej-Bawla Highway, Matoda, Sanand, Ahmedabad- 382213,
Primary Sponsor
Name
Intas Pharmaceutical Ltd India
Address
Intas Plasma
Fractionation Unit, Plot No. 496/1/A&B, SarkhejBawla Highway, Matoda, Sanand, Ahmedabad- 382213, India
Department of Clinical Research,Room no.N/a,All India Institute of Medical Sciences, Sijua, Patrapada, Bhubaneswar, Odisha - 751019 Khordha ORISSA
9438884180
samarendramahapatro@yahoo.com
Dr Sagar Bhattad
Aster- CMI Hospital
Department of Clinical
Research, Room No.
NA, Airport Road, Sahakar Nagar, Hebbal, Bagalore, Bangalore, Karnataka- 560092 Bangalore KARNATAKA
9779433934
drsagar.bhattad@asterhospital.com
Dr Mukesh Desai
Bai Jerbai Wadia Hospital for Children
Department of Inborn Errors of Immunity, Bai Jerbai Wadia Hospital for Children, Acharya Donde Marg, Parel, Mumbai- 400012 Mumbai MAHARASHTRA
9820037087
mmdesai007@gmail.com
Dr Sanjeeva GN Narayachar
Indira Gandhi Institute of child Health, Bangalore
Department of Clinical Research, Room No. NA, Indira Gandhi Institute of child Health, South Hospital Complex, Dharmaram College Post, Bangalore Bangalore KARNATAKA
9945657034
sanju.gn26@gmail.com
Dr Liza Rajsekhar
Nizams Institute Of Medical Sciences
Department of Clinical Research, Room No. NA, Punjagutta Rd, Punjagutta Market, Punjagutta, Hyderabad, Telangana 500082 Hyderabad TELANGANA
9391008618
lizarajasekhar@gmail.com
Dr Nita Radhakrishnan
Post Graduate Institute of Child Health
Department of Clinical Research,Room No NA,Post Graduate Institute of Child Health, Sector 30, NOIDA, Gautam Budh Nagar, Uttar Pradesh, 201303, India Gautam Buddha Nagar UTTAR PRADESH
9999041524
nitark@gmail.com
Dr Puja Srivastava
Radiance Hospital
Department of Clinical Research, Room No. NA, 3rd & 4th Floor, Shital Varsha, opp. Manan Motors, nr. Vijay Char Rasta, Navrangpura, Ahmedabad, Gujarat 380009 Ahmadabad GUJARAT
8155891234
dr.pujasrivastava@gmail.com
Dr Amita Aggarwal
Sanjay Gandhi Postgraduate Institute of Medical Sciencies
Department of Clinical Research, Room No. NA, Department of Clinical Immunology & Rheumatology, SGPGI, Lucknow Lucknow UTTAR PRADESH
9473584267
aa.amita@gmail.com
Dr Shweta Bansal
Sir HN Reliance Foundation & Research Centre
Department of Clinical Research, Room No. NA, Prarthana Samaj, Raja Ram Mohan Roy Rd, Girgaon, Mumbai, Maharashtra 400004 Mumbai MAHARASHTRA
Human normal immunoglobulin intravenous; 5% and 10% solution
Dosage Level(s)- 200-900 mg/kg of body weight every 21 days or 28 days as per the investigator discretion,Route of Administration-IV infusion,Duration of
dosing - IMP will be administered for 12 months at frequency as per Investigator discretion.
Comparator Agent
NA
NA
Inclusion Criteria
Age From
2.00 Year(s)
Age To
65.00 Year(s)
Gender
Both
Details
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.
ExclusionCriteria
Details
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.
20 Participant has known substance or prescription drug abuse.21 Participant had major surgery within 4 weeks before screening, or will not have fully
recovered from surgery, or has surgery planned during the time the participant is expected to
participate in the study.
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.
Method of Generating Random Sequence
Not Applicable
Method of Concealment
Not Applicable
Blinding/Masking
Not Applicable
Primary Outcome
Outcome
TimePoints
To evaluate the efficacy of human normal immunoglobulin
intravenous preventing serious
bacterial infection (SBI) compared with historical control data in participants with primary immunodeficiency disease.
Per person per year.
Secondary Outcome
Outcome
TimePoints
To evaluate pharmacokinetics of human normal immunoglobulin
intravenous infusion in
participants with primary
immunodeficiency (PID) disease
28-day infusion and 21-day infusion.
Target Sample Size
Total Sample Size="89" Sample Size from India="89" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
23/12/2022
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
Date Missing
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="2" Months="0" Days="0"
Recruitment Status of Trial (Global)
Not Applicable
Recruitment Status of Trial (India)
Not Yet Recruiting
Publication Details
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
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.