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LUNA 3: Study to Evaluate Rilzabrutinib in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP)

Sponsor
Principia Biopharma, a Sanofi Company (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04562766
Collaborator
(none)
224
Enrollment
113
Locations
2
Arms
53.6
Anticipated Duration (Months)
2
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a randomized, double-blind study of rilzabrutinib in patients with persistent or chronic ITP, with an average platelet count of <30,000/μL (and no single platelet count

35,000/μL) on two counts at least 5 days apart in the 14 days before treatment begins. Patients will receive rilzabrutinib or placebo 400mg twice daily.

For each patient, the study will last up to 60 weeks from the start of the Screening Period to the End of Study (EOS) visit. This includes Screening (up to 4 weeks) through a 12 to 24-week Blinded Treatment Period followed by a 28-week Open-Label Period. There is a 4-week post dose follow-up.

Patients who respond per specified criteria at the end of the Open-Label Period will be able to enter a 12-month Long-Term Extension (LTE).

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
224 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double-Blind
Primary Purpose:
Treatment
Official Title:
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel-Group Study With an Open-Label Extension to Evaluate the Efficacy and Safety of Oral Rilzabrutinib (PRN1008) in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP)
Actual Study Start Date :
Dec 14, 2020
Anticipated Primary Completion Date :
Oct 1, 2023
Anticipated Study Completion Date :
Jun 1, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Rilzabrutinib

Patients receive rilzabrutinib 400mg orally twice daily for up to 24 weeks followed by 28 weeks of open label period

Drug: Rilzabrutinib
400mg Caplet
Other Names:
  • PRN1008

    		•
    Placebo Comparator: Placebo

    Patients receive matching placebo 400mg orally twice daily for up to 24 weeks

    Drug: Placebo
    400mg Caplet
    Other Names:
  • PRN1008 Placebo

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Proportion of patients able to achieve platelet counts at or above 50,000/μL for at least 8 out of the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy [24 weeks]

    Secondary Outcome Measures

    1. Incidence of Treatment Emergent Adverse Events [52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose]

      The incidence, severity and relationship of TEAEs during the treatment periods and through the 4-week follow up from the last dose received

    2. Number of weeks with platelet count ≥50,000/μL OR between ≥30,000/μL and <50,000/μL and at least doubled from baseline over the 24-week blinded treatment period in the absence of rescue therapy [24 weeks]

    3. Number of weeks with platelet counts between ≥30,000/μL and <50,000/μL and at least doubled from baseline over the 24-week blinded treatment period in the absence of rescue therapy [24 weeks]

    4. Time to first platelet count of ≥50,000/μL OR between ≥30,000/μL and <50,000/μL and doubled from baseline [24 weeks]

    5. Proportion of patients requiring rescue therapy [24 weeks]

    6. Change from baseline in Idiopathic Thrombocytopenic Purpura Bleeding Scale (IBLS) assessment [52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose]

      The IBLS is a bleeding assessment system comprising 11 site-specific grades from 0 (none) to 2 (marked bleeding) assessed at nine anatomical sites by history over the previous period

    7. Frequency and severity of Treatment Emergent Adverse Events [52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose]

      Including physical examination, ECG, clinical laboratory test results, vital signs and laboratory tests (serum chemistry, hematology, except for platelet counts included in the primary efficacy endpoint)

    8. Frequency and severity of bleeding TEAEs [52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose]

    9. Plasma concentrations of rilzabrutinib [Until 52 weeks]

    10. Change from baseline on the Symptoms, Bother and Activity domains of the ITP Patient Assessment Questionnaire (ITP-PAQ) in adult patients (≥18 years) [52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose]

      The ITP Patient Assessment Questionnaire™ (ITP-PAQ™) is a disease-specific instrument that was designed to measure the Quality of Life (QoL) of adult patients with immune thrombocytopenia. The items employ a 4-week recall with responses recorded on 4-, 5- or 7-point Likert scales. All item scores are transformed to a 0 to 100 continuum where higher scores represent better QoL and are weighted equally to derive the scale scores.

    11. Change from baseline in disease-specific QoL as measured by the Kids' ITP Tools (ITP-KIT) score in patients ages 12 to <18 [52 weeks of treatment, 12 months of long term extension and 4 weeks of follow up post last dose]

      The ITP-KIT include a battery of three disease-specific instruments, a child self-report form designed to be completed by children ≥7 years, a parent proxy report form for children <7 and a parent impact form. Respondents record their disease experience based on a 1-week recall. The instrument yields a total score which is the summation of the items converted to a 0 to 100 score with higher scores indicating better disease-specific QoL.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    1. Patients will be male and female with primary ITP with duration of >6 months in ages 12 to <18 years and duration of >3 months in ages 18 years and above

    2. Patients who had a response (achievement of platelet count ≥50,000/µL) to IVIg/anti-D or CSs that was not sustained and who have documented intolerance, insufficient response or any contra-indication to any appropriate courses of standard of care ITP therapy

    3. An average of 2 platelet counts at least 5 days apart of <30,000/µL (and no single platelet count >35,000/µL) -- Patients from 12 to <18 years of age must additionally be determined to need treatment for ITP as per clinical assessment by the Investigator

    4. Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.5 X 10^9/L, AST/ALT ≤1.5 x upper limit of normal [ULN], albumin ≥3 g/dL, total bilirubin ≤1.5 x ULN [unless the patient has documented Gilbert syndrome], glomerular filtration rate >50 [Cockcroft and Gault method])

    5. Hemoglobin >9 g/dL within 1 week prior to Study Day 1

    6. All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies

    7. Patients must be able to provide written informed consent or informed assent with corresponding informed consent obtained from the patient's guardian and agree to the schedule of assessments

    Exclusion Criteria:

    1. Patients with secondary ITP

    2. Pregnant or lactating women

    3. History (within 5 years of Study Day 1) or current, active malignancy requiring or likely to require chemotherapeutic or surgical treatment during the study, with the exception of non melanoma skin cancer

    4. Transfusion with blood, blood products, plasmapheresis, or use of any other rescue medications with intent to increase platelet count within 14 days before Study Day 1

    5. Change in CS and/or TPO-RA dose within 14 days prior to Study Day 1 (more than 10% variation from current doses)

    6. Immunosuppressant drugs other than CSs within 5 times the elimination half-life of the drug or 14 days of Study Day 1, whichever is longer

    7. Treatment with rituximab or splenectomy within the 3 months prior to Study Day 1

    • Patients treated with rituximab will have normal B-cell counts prior to enrollment
    1. Has received any investigational drug within the 30 days before receiving the first dose of study medication, or at least 5 times elimination half-life of the drug (whichever is longer); patient should not be using an investigational device at the time of dosing

    • Patients who previously received treatment with Bruton's Tyrosine Kinase (BTK) inhibitors (except rilzabrutinib) within 30 days before the first dose of study drug are not eligible

    • Patients who previously received rilzabrutinib at any time are not eligible

    1. History of solid organ transplant

    2. Myelodysplastic syndrome

    3. Live vaccine within 28 days prior to Study Day 1 or plan to receive one during the study

    4. Planned surgery in the time frame of the dosing period

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Southern California_Investigational Site Number 84024 Los Angeles California United States 90033
    2 UCSF Benioff Children's Hospital San Franciso_Investigational Site Number 84020 Oakland California United States 94158
    3 Lundquist Institute for Biomedical Innovation at Harbor UCLA Medical Center_Investigational Site Number 84037 Torrance California United States 00000
    4 The Oncology Institute of Hope and Innovation_Investigational Site Number 84031 Whittier California United States 00000
    5 Children's Hospital Colorado_Investigational Site Number 84025 Aurora Colorado United States 00000
    6 IMMUNOe International Research Centers_Investigational Site Number 84028 Centennial Colorado United States 80112
    7 ASCLEPES Research Centers_Investigational Site Number 84023 Weeki Wachee Florida United States 34607
    8 Children's Healthcare of Atlanta_Investigational Site Number 84034 Atlanta Georgia United States 00000
    9 Rush University Medical Center_Investigational Site Number 84029 Chicago Illinois United States 60612
    10 University of Louisville - James Graham Brown Cancer Center_Investigational Site Number 84033 Louisville Kentucky United States 00000
    11 Montefiore Medical Center_Investigational Site Number 84032 Bronx New York United States 00000
    12 Cleveland Clinic_Investigational Site Number 84026 Cleveland Ohio United States 44195
    13 The Children's Hospital of Philadelphia (CHOP)_Investigational Site Number 84027 Philadelphia Pennsylvania United States 19104
    14 University of Utah-Huntsman Cancer Institute_Investigational Site Number 84035 Salt Lake City Utah United States 00000
    15 Investigational Site Number 03206 Capital Federal Argentina C1280AEB
    16 Investigational Site Number 03205 Cordoba Argentina X5003DCE
    17 Investigational Site Number 03209 Corrientes Argentina W3410FND
    18 Investigational Site Number 03208 San Juan Argentina J5402DIL
    19 Investigational Site Number 03609 Adelaide Australia 5000
    20 Investigational Site Number 03606 Frankston Australia 3199
    21 Investigational Site Number 03607 Kogarah Australia 2217
    22 Investigational Site Number 03610 Perth Australia 6000
    23 Investigational Site Number 03611 Queensland Australia 41001
    24 Investigational Site Number 03608 Westmead Australia 2145
    25 Investigational Site Number 04005 Graz Austria 8036
    26 Investigational Site Number 04004 Leoben Austria 8700
    27 Investigational Site Number 04001 Linz Austria 4020
    28 Investigational Site Number 04003 Steyr Austria 24204
    29 Investigational Site Number 04002 Wien Austria 1140
    30 Investigational Site Number 07606 Belem Do Para Brazil 66053-000
    31 Investigational Site Number 07610 Cascavel Brazil 85806-300
    32 Investigational Site Number 07605 Porto Alegre Brazil 90035-903
    33 Investigational Site Number 07609 Rio de Janeiro Brazil 20211-030
    34 Investigational Site Number 07608 Salvador Brazil V
    35 Investigational Site Number 07607 Sao Paulo Brazil 04039-004
    36 Investigational Site Number 07611 São Paulo Brazil 08270-070
    37 CHU Sainte-Justine_Investigational site number 12405 Montréal Canada
    38 Investigational Site Number 15201 La Serena Chile
    39 Investigational Site Number 15204 Santiago Chile
    40 Investigational Site Number 15202 Viña Del Mar Chile 322000
    41 Investigational Site Number 25011 Créteil France 94010
    42 Investigational Site Number 25010 Dijon France 21000
    43 Investigational Site Number 25009 Nantes Cedex France 44093
    44 Investigational Site Number 25008 Paris France 75012
    45 Investigational Site Number 25012 Paris France 75019
    46 Investigational Site Number 25007 Pessac France 33064
    47 Investigational Site Number 27610 Berlin Germany 10117
    48 Investigational Site Number 27612 Düsseldorf Germany
    49 Investigational Site Number 27613 Frankfurt am Main Germany D-60590
    50 Investigational Site Number 27611 Recklinghausen Germany 45659
    51 Investigational Site Number 34803 Budapest Hungary
    52 Investigational Site Number 34805 Debrecen Hungary V
    53 Investigational Site Number 34801 Győr Hungary
    54 Investigational Site Number 34804 Nyíregyháza Hungary 4400
    55 Investigational Site Number 34802 Szekesfehervar Hungary 8000
    56 Investigational Site Number 37605 Haifa Israel 3109601
    57 Investigational Site Number 37606 Kfar Saba Israel 44281
    58 Investigational Site Number 37607 Tel Aviv Israel 6423906
    59 Investigational Site Number 37608 Tel HaShomer Israel 5265601
    60 Investigational Site Number 37609 Zerifin Israel 70300
    61 Investigational Site Number 38012 Bologna Italy 40138
    62 Investigational Site Number 38014 Firenze Italy
    63 Investigational Site Number 38013 Milano Italy
    64 Investigational Site Number 38015 Rome Italy 000168
    65 Investigational Site Number 38010 Trieste Italy 34125
    66 Investigational Site Number 38011 Vicenza Italy 36100
    67 Investigational Site Number 41004 Busan Korea, Republic of 49241
    68 Investigational Site Number 41001 Gyeonggi-do Korea, Republic of 16499
    69 Investigational Site Number 41003 Seoul Korea, Republic of 02841
    70 Investigational Site Number 41005 Seoul Korea, Republic of 3080
    71 Investigational Site Number 41006 Seoul Korea, Republic of 3722
    72 Investigational Site Number 48402 Chihuahua Mexico
    73 Investigational Site Number 48406 Ciudad de mexico Mexico
    74 Investigational Site Number 48405 Distrito Federal Mexico
    75 Investigational Site Number 48404 Durango Mexico
    76 Investigational Site Number 48401 Monterrey Mexico
    77 Investigational Site Number 48403 Zapopan Mexico
    78 Investigational Site Number 57802 Bergen Norway 5021
    79 Investigational Site Number 57801 Grålum Norway 1714
    80 Investigational Site Number 61615 Gdynia Poland 81-519
    81 Investigational Site Number 61617 Piła Poland
    82 Investigational Site Number 61609 Słupsk Poland 76-200
    83 Investigational Site Number 61612 Warszawa Poland
    84 Investigational Site Number 64307 Moscow Russian Federation 119049
    85 Investigational Site Number 64305 Moscow Russian Federation
    86 Investigational Site Number 64304 Novosibirsk Russian Federation 630091
    87 Investigational Site Number 64301 Pyatigorsk Russian Federation 357502
    88 Investigational Site Number 64302 Saint Petersburg Russian Federation 191024
    89 Investigational Site Number 64306 Samara Russian Federation 443099
    90 Investigational Site Number 64303 Tula Russian Federation 300053
    91 Investigational Site Number 70201 Singapore Singapore 119074
    92 Investigational Site Number 70202 Singapore Singapore 169608
    93 Investigational Site Number 70203 Singapore Singapore 308433
    94 Investigational Site Number 72409 Barcelona Spain 08025
    95 Investigational Site Number 72410 Madrid Spain 28046
    96 Investigational Site Number 72412 Madrid Spain 28046
    97 Investigational Site Number 72408 Malaga Spain 29010
    98 Investigational Site Number 72411 Murcia Spain 30008
    99 Investigational Site Number 72413 Sevilla Spain
    100 Investigational Site Number 72407 Valencia Spain 46010
    101 Investigational Site Number 76405 Bangkok Thailand 10330
    102 Investigational Site Number 76404 Bangkok Thailand
    103 Investigational Site Number 76402 Chiang Mai Thailand 50200
    104 Investigational Site Number 76401 Khon Kaen Thailand 40002
    105 Investigational Site Number 76403 Songkla Thailand 90110
    106 Investigational Site Number 79208 Ankara Turkey
    107 Investigational Site Number 79210 Istanbul Turkey 34093
    108 Investigational Site Number 79206 Izmir Turkey 35100
    109 Investigational Site Number 79209 Kayseri Turkey 38030
    110 Investigational Site Number 80408 Dnipropetrovs'k Ukraine 49102
    111 Investigational Site Number 80409 Kryvyi Rih City Ukraine 50025
    112 Investigational Site Number 80410 Kyiv Ukraine 3143
    113 Investigational Site Number 82605 Norfolk United Kingdom Norfolk

    Sponsors and Collaborators

    • Principia Biopharma, a Sanofi Company

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Principia Biopharma, a Sanofi Company
    ClinicalTrials.gov Identifier:
    NCT04562766
    Other Study ID Numbers:
    • EFC17093
    • PRN1008-018
    First Posted:
    Sep 24, 2020
    Last Update Posted:
    May 20, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Thrombocytopenia
    Purpura, Thrombocytopenic, Idiopathic

    Study Results

    No Results Posted as of May 20, 2022