Rituximab Therapy in Refractory Adult and Juvenile Idiopathic Inflammatory Myopathy (IIM)
Rituximab for the Treatment of Refractory Adult and Juvenile Dermatomyositis (DM) and Adult Polymyositis (PM)
Sponsors
Lead Sponsor
Collaborators
Source
University of Pittsburgh
Oversight Info
Has Dmc
Yes
Brief Summary
Rituximab is a man-made antibody used to treat certain types of cancer. This study will
determine whether rituximab is an effective treatment for adult and pediatric patients with
dermatomyositis or polymyositis.
Study hypotheses: 1) The time to improvement in Group A patients (receiving rituximab first)
will occur significantly earlier than in Group B patients (receiving rituximab later). 2) The
proportion of patients improved at Week 8 of the treatment phase will be significantly
greater in Group A than in Group B.
determine whether rituximab is an effective treatment for adult and pediatric patients with
dermatomyositis or polymyositis.
Study hypotheses: 1) The time to improvement in Group A patients (receiving rituximab first)
will occur significantly earlier than in Group B patients (receiving rituximab later). 2) The
proportion of patients improved at Week 8 of the treatment phase will be significantly
greater in Group A than in Group B.
Detailed Description
Rituximab is a chimeric, murine-human, genetically engineered monoclonal antibody directed
against the CD20 (cluster of differentiation antigen 20) antigen found on the surface of
B-lymphocytes and is known to deplete B cells when administered intravenously. It is approved
to treat non-Hodgkin's lymphoma. Rituximab has been used for autoimmune diseases such as
systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and immune-mediated
hematologic disorders. It has also been studied and used in small numbers of patients with
myositis. This study will evaluate the efficacy of rituximab in treating refractory adult and
pediatric patients with dermatomyositis and adult polymyositis.
A patient's participation in this study will last approximately 45 weeks. At screening,
participants will have a physical exam, muscle strength assessment, an electrocardiogram, and
blood and urine collection; they will also be asked to complete several questionnaires. All
participants will receive 2 infusions of rituximab and 2 infusions of placebo. Participants
will be randomly assigned to one of two groups. Group A will receive rituximab at Weeks 0 and
1 and placebo at Weeks 8 and 9. Group B will receive placebo at Weeks 0 and 1 and rituximab
at Weeks 8 and 9. Each infusion will be given on an outpatient basis over a minimum of
approximately 5 hours' time.
There will be a total of 14 study visits. All participants will visit the outpatient clinic
at selected time points for muscle strength testing, a physical exam, disease activity
measurements, and blood collection. During the study, participants will be monitored closely
for improvement or worsening of their disease and for serious drug related side effects. Some
participants will be asked if they are willing to undergo 2 muscle biopsy procedures, 1 prior
to receiving study medication and 1 after receiving study medication, to determine the
effects of rituximab on muscle tissue.
If a participant is unable to locate a near-by clinical center, the adult and pediatric
centers at the National Institute of Health located in Bethesda, Maryland have funds
available to assist with travel costs.
NIH SUB-STUDY: "Rituximab to Treat Dermatomyositis and Polymyositis"
- This study is currently recruiting patients.
- Sponsored by: National Institute of Environmental Health Sciences (NIEHS)
- Information provided by: National Institutes of Health Clinical Center (CC)
- Expected Total Enrollment: 30
- Study start: October 2006
- Location and Contact Information: Patient Recruitment and Public Liaison Office;(800)
411-1222; prpl@mail.cc.nih.gov; Phone: 1-866-411-1010
The NIH sub-study will take advantage of the multi-center core RIM trial to identify changes
in gene expression patterns in muscle, skin, and peripheral blood and the imaging features
and immunopathology of muscle, skin, and peripheral cells before (week 0) and after (week 16)
therapy. These changes will also be correlated with the large number of clinical, laboratory,
and research variables already planned to be collected in the core RIM Study. Furthermore,
knowing specifically which gene expression patterns are altered in resistant patients before
rituximab, and which are changed after rituximab therapy - in conjunction with flow cytometry
of peripheral cells and immunopathology of the tissues - will help in understanding more
about the pathogenesis of myositis and the possible contribution of B lymphocytes and their
subsets.
Patients with dermatomyositis and polymyositis who meet the inclusion/exclusion criteria for
the core RIM trial may be eligible for this sub-study. The following procedures will be
conducted in addition to the core RIM trial procedures during the 13 clinic visits over a
period of 44 weeks:
- Weeks 0, 16: Muscle and skin biopsy (adult only). Small samples of muscle and skin
tissue will be surgically removed for examination under a microscope.
- Weeks 0, 8, 16, 44: Skin evaluation and photography. The effect of the disease on the
skin will be thoroughly evaluated and photographs of any rashes and of the skin around
the nails will be taken.
- Weeks 0, 8, 16, 44: Magnetic resonance imaging (MRI). All participants will have MRI
scans of the skin and of the muscle in the legs. Adults will also have an MRI to examine
blood flow in the muscle.
against the CD20 (cluster of differentiation antigen 20) antigen found on the surface of
B-lymphocytes and is known to deplete B cells when administered intravenously. It is approved
to treat non-Hodgkin's lymphoma. Rituximab has been used for autoimmune diseases such as
systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and immune-mediated
hematologic disorders. It has also been studied and used in small numbers of patients with
myositis. This study will evaluate the efficacy of rituximab in treating refractory adult and
pediatric patients with dermatomyositis and adult polymyositis.
A patient's participation in this study will last approximately 45 weeks. At screening,
participants will have a physical exam, muscle strength assessment, an electrocardiogram, and
blood and urine collection; they will also be asked to complete several questionnaires. All
participants will receive 2 infusions of rituximab and 2 infusions of placebo. Participants
will be randomly assigned to one of two groups. Group A will receive rituximab at Weeks 0 and
1 and placebo at Weeks 8 and 9. Group B will receive placebo at Weeks 0 and 1 and rituximab
at Weeks 8 and 9. Each infusion will be given on an outpatient basis over a minimum of
approximately 5 hours' time.
There will be a total of 14 study visits. All participants will visit the outpatient clinic
at selected time points for muscle strength testing, a physical exam, disease activity
measurements, and blood collection. During the study, participants will be monitored closely
for improvement or worsening of their disease and for serious drug related side effects. Some
participants will be asked if they are willing to undergo 2 muscle biopsy procedures, 1 prior
to receiving study medication and 1 after receiving study medication, to determine the
effects of rituximab on muscle tissue.
If a participant is unable to locate a near-by clinical center, the adult and pediatric
centers at the National Institute of Health located in Bethesda, Maryland have funds
available to assist with travel costs.
NIH SUB-STUDY: "Rituximab to Treat Dermatomyositis and Polymyositis"
- This study is currently recruiting patients.
- Sponsored by: National Institute of Environmental Health Sciences (NIEHS)
- Information provided by: National Institutes of Health Clinical Center (CC)
- Expected Total Enrollment: 30
- Study start: October 2006
- Location and Contact Information: Patient Recruitment and Public Liaison Office;(800)
411-1222; prpl@mail.cc.nih.gov; Phone: 1-866-411-1010
The NIH sub-study will take advantage of the multi-center core RIM trial to identify changes
in gene expression patterns in muscle, skin, and peripheral blood and the imaging features
and immunopathology of muscle, skin, and peripheral cells before (week 0) and after (week 16)
therapy. These changes will also be correlated with the large number of clinical, laboratory,
and research variables already planned to be collected in the core RIM Study. Furthermore,
knowing specifically which gene expression patterns are altered in resistant patients before
rituximab, and which are changed after rituximab therapy - in conjunction with flow cytometry
of peripheral cells and immunopathology of the tissues - will help in understanding more
about the pathogenesis of myositis and the possible contribution of B lymphocytes and their
subsets.
Patients with dermatomyositis and polymyositis who meet the inclusion/exclusion criteria for
the core RIM trial may be eligible for this sub-study. The following procedures will be
conducted in addition to the core RIM trial procedures during the 13 clinic visits over a
period of 44 weeks:
- Weeks 0, 16: Muscle and skin biopsy (adult only). Small samples of muscle and skin
tissue will be surgically removed for examination under a microscope.
- Weeks 0, 8, 16, 44: Skin evaluation and photography. The effect of the disease on the
skin will be thoroughly evaluated and photographs of any rashes and of the skin around
the nails will be taken.
- Weeks 0, 8, 16, 44: Magnetic resonance imaging (MRI). All participants will have MRI
scans of the skin and of the muscle in the legs. Adults will also have an MRI to examine
blood flow in the muscle.
Overall Status
Completed
Start Date
2006-03-01
Completion Date
2010-08-01
Primary Completion Date
2010-02-01
Phase
Phase 2
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
|
Comparison Between the Time to Improvement Between the Two Groups of IIM (Idiopathic Inflammatory Myopathy) Patients |
Week 44 of treatment phase |
Secondary Outcome
Measure |
Time Frame |
|
Response Rates (Proportion of Improved Patients) Between Groups A (Rituximab Wks 0 and 1) and B (Rituximab Wks 8 and 9) at Week 8 |
Week 8 of the treatment phase |
|
20% Improvement in Manual Muscle Testing (MMT) Over Baseline on Two Consecutive Time Points (Muscle is the Primary Organ of Involvement, and MMT is the One Objective Measurement of the Definition of Improvement [DOI]) |
Week 44 of treatment phase |
Enrollment
200
Conditions
Intervention
Intervention Type
Drug
Intervention Name
Description
Treatment Group A - intravenous rituximab 750mg/m2 BSA (Body Surface Area) up to a maximum dose of 1 gram at Weeks 0 and 1 Group B - intravenous rituximab 750mg/m2 BSA (Body Surface Area) up to a maximum does of 1 gram at Weeks 8 and 9
Arm Group Label
Adult Study Group 1
Adult Study Group 2
Adult Study Group 3
Adult Study Group 4
JDM Study Group 1
JDM Study Group 2
Other Name
Rituxan
Intervention Type
Drug
Intervention Name
Description
Treatment Group A: placebo infusion at Weeks 8 and 9
Treatment Group B: placebo infusion at Weeks 0 and 1
Treatment Group B: placebo infusion at Weeks 0 and 1
Arm Group Label
Adult Study Group 1
Adult Study Group 2
Adult Study Group 3
Adult Study Group 4
JDM Study Group 1
JDM Study Group 2
Eligibility
Criteria
Inclusion Criteria:
- Adults with definite or probable dermatomyositis or polymyositis and pediatric
patients five years of age and over with definite or probable juvenile dermatomyositis
(JDM) by Bohan and Peter criteria. Diagnosis of JDM based on an age of onset (i.e.,
first symptom of myositis or dermatomyositis rash) is less 18 years of age
- Refractory myositis, defined by intolerance to or inadequate response to
corticosteroids plus an adequate regime of at least one other immunosuppressive agent.
Intolerance is defined as side effects that require discontinuation of the medication
or an underlying condition that precludes further use of the medication.
- Baseline manual muscle testing which is based on a maximum MMT-8 (Manual Muscle Test)
score of 150:Adult subjects with dermatomyositis (DM) or polymyositis (PM) must have a
score that is no greater than 125/150 in conjunction with 2 other abnormal core set
measures.
Subjects with a diagnosis of Juvenile Dermatomyositis (JDM) must meet either of the
following criteria:
1. An MMT-8 (Manual Muscle Test) score that is no greater than 125/150 in conjunction
with 2 other abnormal core set measures.
OR
2. If MMT (Manual Muscle Test) score is greater than 125/150 the patient MUST meet at
least 3 abnormal core set measures.
- Background therapy with at least 1 non-corticosteroid immunosuppressive agent at
a stable dose for at least 6 weeks prior to screening
- Able and willing to complete self-report questionnaires. Parents of pediatric
participants will be required to complete the questionnaires on behalf of their
children.
- Willing to use acceptable forms of contraception for the duration of the study
for patients of reproductive potential.
- Parent willing to provide informed consent, if applicable
- Willing to forgo immunization with a live vaccine for the duration of the study
Exclusion Criteria:
- Drug-induced myositis. Patients who have myositis or myopathic syndromes caused by
taking medications known to induce myositis-like syndromes, including but not limited
to statin agents, fibric acid derivatives, colchicine, and hydroxychloroquine.
- Juvenile polymyositis
- Inclusion body myositis
- Cancer-associated myositis, defined as the diagnosis of myositis within 2 years of the
diagnosis of cancer. Patients with basal or squamous cell skin cancer or carcinoma in
situ of the cervix are not excluded, if it has been at least 5 years since excision.
- Myositis in overlap with another connective tissue disease that may preclude the
accurate assessment of a treatment response
- Live viral vaccine within 4 weeks prior to study entry
- Any joint disease or other musculoskeletal condition that may interfere with muscle
strength testing
- Known hypersensitivity to mouse proteins
- Any concomitant or life-threatening non-myositis illness that, in the opinion of the
investigator, may interfere with the study
- Known or suspected history of drug or alcohol abuse within the last 6 months prior to
study entry, as determined by medical record or patient interview
- Anticipated poor compliance with study requirements
- Participation in another clinical trial within 30 days prior to screening
- Any history or evidence of any severe illness or other condition that, in the opinion
of the investigator, may interfere with the study
- Previously received rituximab
- Evidence of prior infection with hepatitis B or hepatitis C virus
- Initiation of an exercise program within 4 weeks of screening OR initiation of an
exercise program during the study
- Consumed any creatine-containing, over-the-counter products in the form of dietary
supplements 30 days prior to screening visit and for the duration of the study
- Adults with definite or probable dermatomyositis or polymyositis and pediatric
patients five years of age and over with definite or probable juvenile dermatomyositis
(JDM) by Bohan and Peter criteria. Diagnosis of JDM based on an age of onset (i.e.,
first symptom of myositis or dermatomyositis rash) is less 18 years of age
- Refractory myositis, defined by intolerance to or inadequate response to
corticosteroids plus an adequate regime of at least one other immunosuppressive agent.
Intolerance is defined as side effects that require discontinuation of the medication
or an underlying condition that precludes further use of the medication.
- Baseline manual muscle testing which is based on a maximum MMT-8 (Manual Muscle Test)
score of 150:Adult subjects with dermatomyositis (DM) or polymyositis (PM) must have a
score that is no greater than 125/150 in conjunction with 2 other abnormal core set
measures.
Subjects with a diagnosis of Juvenile Dermatomyositis (JDM) must meet either of the
following criteria:
1. An MMT-8 (Manual Muscle Test) score that is no greater than 125/150 in conjunction
with 2 other abnormal core set measures.
OR
2. If MMT (Manual Muscle Test) score is greater than 125/150 the patient MUST meet at
least 3 abnormal core set measures.
- Background therapy with at least 1 non-corticosteroid immunosuppressive agent at
a stable dose for at least 6 weeks prior to screening
- Able and willing to complete self-report questionnaires. Parents of pediatric
participants will be required to complete the questionnaires on behalf of their
children.
- Willing to use acceptable forms of contraception for the duration of the study
for patients of reproductive potential.
- Parent willing to provide informed consent, if applicable
- Willing to forgo immunization with a live vaccine for the duration of the study
Exclusion Criteria:
- Drug-induced myositis. Patients who have myositis or myopathic syndromes caused by
taking medications known to induce myositis-like syndromes, including but not limited
to statin agents, fibric acid derivatives, colchicine, and hydroxychloroquine.
- Juvenile polymyositis
- Inclusion body myositis
- Cancer-associated myositis, defined as the diagnosis of myositis within 2 years of the
diagnosis of cancer. Patients with basal or squamous cell skin cancer or carcinoma in
situ of the cervix are not excluded, if it has been at least 5 years since excision.
- Myositis in overlap with another connective tissue disease that may preclude the
accurate assessment of a treatment response
- Live viral vaccine within 4 weeks prior to study entry
- Any joint disease or other musculoskeletal condition that may interfere with muscle
strength testing
- Known hypersensitivity to mouse proteins
- Any concomitant or life-threatening non-myositis illness that, in the opinion of the
investigator, may interfere with the study
- Known or suspected history of drug or alcohol abuse within the last 6 months prior to
study entry, as determined by medical record or patient interview
- Anticipated poor compliance with study requirements
- Participation in another clinical trial within 30 days prior to screening
- Any history or evidence of any severe illness or other condition that, in the opinion
of the investigator, may interfere with the study
- Previously received rituximab
- Evidence of prior infection with hepatitis B or hepatitis C virus
- Initiation of an exercise program within 4 weeks of screening OR initiation of an
exercise program during the study
- Consumed any creatine-containing, over-the-counter products in the form of dietary
supplements 30 days prior to screening visit and for the duration of the study
Gender
All
Minimum Age
5 Years
Maximum Age
N/A
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
|
Chester V. Oddis, MD |
Principal Investigator |
University of Pittsburgh |
|
Ann M. Reed, MD |
Principal Investigator |
Mayo Clinic |
Location
Facility |
|
University of Alabama Arthritis Intervention Program (Adult Site) Birmingham Alabama 35294 United States |
|
Phoenix Neurological Associates, LTD (Adult Site) Phoenix Arizona 85006 United States |
|
Cedars-Sinai Medical Center (Adult Site) Los Angeles California 90048 United States |
|
Stanford University (Adult Site) Stanford California 94305 United States |
|
Stanford University (Pediatric Site) Stanford California 94305 United States |
|
University of Miami School of Medicine (Adult Site) Miami Florida 33136 United States |
|
Miami Children's Hospital (Pediatric Site) Miami Florida 33155 United States |
|
University of Kansas Medical Center (Adult Site) Kansas City Kansas 66160 United States |
|
Kentucky Clinic (Adult Site) Lexington Kentucky 40536 United States |
|
National Institute of Health (Adult Site) Bethesda Maryland 20892 United States |
|
National Institute of Health (Pediatric Site) Bethesda Maryland 20892 United States |
|
Children's Hospital of Boston (Pediatric Site) Boston Massachusetts 02115 United States |
|
Beth Israel Deaconess Medical Center (Adult Site) Boston Massachusetts 02215 United States |
|
University of Michigan Health System (Adult Site) Ann Arbor Michigan 48109 United States |
|
Michigan State University (Adult and Pediatric Site) Grand Rapids Michigan 49546 United States |
|
Mayo Clinic (Adult Site) Rochester Minnesota 55905 United States |
|
Mayo Clinic (Pediatric Site) Rochester Minnesota 55905 United States |
|
North Shore Long Island Jewish Health System (Adult Site) Lake Success New York 11042 United States |
|
Hospital for Special Surgery (Adult Site) New York New York 10021 United States |
|
Duke University Medical Center (Pediatric Site) Durham North Carolina 27710 United States |
|
Cincinnati's Children's Hospital (Pediatric Site) Cincinnati Ohio 45229 United States |
|
Children's Hospital of Philadelphia (Pediatric Site) Philadelphia Pennsylvania 19104 United States |
|
University of Pennsylvania (Adult Site) Philadelphia Pennsylvania 19104 United States |
|
Children's Hospital of Pittsburgh (Pediatric Site) Pittsburgh Pennsylvania 15213 United States |
|
University of Pittsburgh / UPMC (Adult Site) Pittsburgh Pennsylvania 15261 United States |
|
University of Texas Southwestern Medical Center (Adult) Dallas Texas 75390-8884 United States |
|
Medical College of Wisconsin / Froedtert Memorial Luthern Hospital (Adult Site) Milwaukee Wisconsin 53226 United States |
|
IWK Health Centre Halifax Nova Scotia B3K 6R8 Canada |
|
Hospital for Sick Children (Pediatric Site) Toronto Ontario M5G 1X8 Canada |
|
Institute of Rheumatology Prague Czech Republic |
|
Karolinska Institute Stockholm Sweden |
Location Countries
Country
Canada
Czech Republic
Sweden
United States
Verification Date
2015-03-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Principal Investigator
Investigator Affiliation
University of Pittsburgh
Investigator Full Name
Chester Oddis
Investigator Title
MD, Professor of Medicine, University of Pittsburgh, Division of Rheumatology and Clinical Immunology
Keywords
Has Expanded Access
No
Condition Browse
Secondary Id
5R01AR061298-02
HHSN26420042273C
Number Of Arms
6
Intervention Browse
Mesh Term
Rituximab
Arm Group
Arm Group Label
Adult Study Group 1
Arm Group Type
Experimental
Description
Refractory adult polymyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A)
Arm Group Label
Adult Study Group 2
Arm Group Type
Experimental
Description
Refractory adult polymyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)
Arm Group Label
Adult Study Group 3
Arm Group Type
Experimental
Description
Adult dermatomyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A)
Arm Group Label
Adult Study Group 4
Arm Group Type
Experimental
Description
Adult dermatomyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)
Arm Group Label
JDM Study Group 1
Arm Group Type
Experimental
Description
Refractory juvenile dermatomyositis patients who will receive rituximab at Weeks 0 and 1 followed by placebo at Weeks 8 and 9 (Treatment Group A)
Arm Group Label
JDM Study Group 2
Arm Group Type
Experimental
Description
Refractory juvenile dermatomyositis patients who will receive placebo at Weeks 0 and 1 followed by rituximab at Weeks 8 and 9 (Treatment Group B)
Results Reference
Citation
Oddis CV, Reed AM, Aggarwal R, Rider LG, Ascherman DP, Levesque MC, Barohn RJ, Feldman BM, Harris-Love MO, Koontz DC, Fertig N, Kelley SS, Pryber SL, Miller FW, Rockette HE; RIM Study Group. Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: a randomized, placebo-phase trial. Arthritis Rheum. 2013 Feb;65(2):314-24. doi: 10.1002/art.37754.
PMID
23124935
Firstreceived Results Date
N/A
Reference
Citation
Feldman B, Wang E, Willan A, Szalai JP. The randomized placebo-phase design for clinical trials. J Clin Epidemiol. 2001 Jun;54(6):550-7.
PMID
11377114
Citation
Levine TD. Rituximab in the treatment of dermatomyositis: an open-label pilot study. Arthritis Rheum. 2005 Feb;52(2):601-7.
PMID
15692974
Removed Countries
Country
United Kingdom
Nct Alias
NCT00393237
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Triple (Participant, Care Provider, Investigator)
Study First Submitted
March 21, 2005
Study First Submitted Qc
March 21, 2005
Study First Posted
March 22, 2005
Last Update Submitted
March 3, 2015
Last Update Submitted Qc
March 3, 2015
Last Update Posted
March 4, 2015
Results First Submitted
October 10, 2013
Results First Submitted Qc
March 3, 2015
Results First Posted
March 4, 2015
ClinicalTrials.gov processed this data on August 24, 2018
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.