A Safety Study of SYNT001 in Participants With Warm Autoimmune Hemolytic Anemia (WAIHA)

Sponsor
Alexion Pharmaceuticals (Industry)
Overall Status
Terminated
CT.gov ID
NCT03075878
Collaborator
(none)
8
10
2
18.8
0.8
0

Study Details

Study Description

Brief Summary

This main study objective was to evaluate the safety and tolerability of intravenous (IV) SYNT001 (ALXN1830) in participants with WAIHA.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

Detailed Description

This study planned to evaluate 2 cohorts: Cohort 1, up to 8 participants to receive IV doses of ALXN1830 (SYNT001 Dose 1); Cohort 2, up to 12 participants to receive IV doses of ALXN1830 (SYNT001 Dose 2).

This study was terminated after the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy were characterized in participants with WAIHA in Cohort 1 (SYNT001 Dose 1), before any participants were enrolled in Cohort 2.

Study Design

Study Type:
Interventional
Actual Enrollment :
8 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1B/2, Multicenter, Open-Label, Safety, Tolerability, and Activity Study of SYNT001 in Patients With Warm Autoimmune Hemolytic Anemia (WAIHA)
Actual Study Start Date :
Jan 10, 2018
Actual Primary Completion Date :
Apr 15, 2019
Actual Study Completion Date :
Aug 6, 2019

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort 1: ALXN1830

SYNT001 Dose 1

Drug: ALXN1830
Administered via IV infusion.
Other Names:
  • SYNT001
  • Experimental: Cohort 2: ALXN1830

    SYNT001 Dose 2

    Drug: ALXN1830
    Administered via IV infusion.
    Other Names:
  • SYNT001
  • Outcome Measures

    Primary Outcome Measures

    1. Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs) [Day 0 (after first dose) through Day 112]

      A TEAE was defined as any adverse event that starts on or after the first dose of study drug or occurs prior to the first dose and worsens in severity on or after the first dose of study drug, during the Treatment Period and Follow-up Period. A TEAE was considered "serious" if, in the view of either the investigator or sponsor, it resulted in any of the following outcomes: death, life-threatening adverse drug event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect, or an event that may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the previously listed outcomes. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. All serious TEAEs were not considered related to the study drug.

    Secondary Outcome Measures

    1. Maximum Serum Concentration (Cmax) On Day 0 And Day 28 [Predose, 5 minutes, 2, 4, 6, 24, and 48 hours, and 5 days postdose]

      The Cmax was determined directly from the concentration-time profile. Starting on Days 0 and 28, serum samples were collected just prior to the start of study drug infusion (predose), at 5 minutes, at 2, 4, 6, 24, and 48 hours, and at 5 days postdose after the end-of-study drug infusion. Results are reported in micrograms/milliliter (ug/mL).

    2. Change From Baseline In Reticulocyte Count At Day 33 [Baseline, Day 33]

      Reticulocyte count was measured as a PD biomarker. Pharmacodynamic samples were collected for analyses throughout the study prior to infusion of study drug for Cohort 1. Measurements for PD biomarkers were derived from the laboratory results. Results are reported in cells/liter (cells*10^12/L). A decrease in reticulocyte count indicated a potential improvement in condition.

    3. Change From Baseline In Hemoglobin At Day 33 [Baseline, Day 33]

      Hemoglobin was measured as a PD biomarker. Pharmacodynamic samples were collected for analyses throughout the study prior to infusion of study drug for Cohort 1. Measurements for PD biomarkers were derived from the laboratory results. Results are reported in grams/deciliter (g/dL). An increase in hemoglobin indicated a potential improvement in condition.

    4. Immunogenicity Of ALXN1830 At Day 112, As Assessed By Anti-ALXN1830 Antibody Level [Day 112]

      Immunogenicity analyses are reported for Day 112. Testing was carried out to detect binding antidrug antibodies by anti-ALXN1830 antibody level. Results are reported as the reciprocal of the titer where they cross the study cut point.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    Participants had to meet the following criteria to be included:
    • Willing and able to read, understand, and sign an informed consent form

    • Confirmed diagnosis of WAIHA by enrolling physician

    • Must have used medically acceptable contraception

    Exclusion Criteria:
    Participants who met any of the following criteria were excluded:
    • Participant unable or unwilling to comply with the protocol

    • Active non-hematologic malignancy or history of non-hematologic malignancy in the 3 years prior to screening (exclusive of non-melanoma skin cancer and cervical cancer in situ)

    • Positive for human immunodeficiency virus or hepatitis C antibody

    • Positive for hepatitis B surface antigen

    • Any exposure to an investigational drug or device within the 30 days prior to screening

    • Intravenous immunoglobulin treatment within 30 days of screening

    • Plasmapheresis or immunoadsorption within 30 days of screening

    • Participant had any current medical condition that, in the opinion of the Investigator, may have compromised their safety or compliance, precluded successful conduct of the study, or interfered with interpretation of the results

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Alexion Study Site Los Angeles California United States 90033
    2 Alexion Study Site San Francisco California United States 94143
    3 Alexion Study Site Boston Massachusetts United States 02114
    4 Alexion Study Site Pittsfield Massachusetts United States 01201
    5 Alexion Study Site Rochester Minnesota United States 55905
    6 Alexion Study Site Cleveland Ohio United States 44106
    7 Alexion Study Site Philadelphia Pennsylvania United States 19104
    8 Alexion Study Site Pittsburgh Pennsylvania United States 15232
    9 Alexion Study Site Seattle Washington United States 98195
    10 Alexion Study Site Amman Jordan 11941

    Sponsors and Collaborators

    • Alexion Pharmaceuticals

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Alexion Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03075878
    Other Study ID Numbers:
    • SYNT001-102
    First Posted:
    Mar 9, 2017
    Last Update Posted:
    May 13, 2020
    Last Verified:
    May 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail This study was terminated after the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy were characterized in Cohort 1 (SYNT001 Dose 1), before any participants were enrolled in Cohort 2 (SYNT001 Dose 2). This results disclosure is for Cohort 1 only.
    Arm/Group Title Cohort 1: ALXN1830
    Arm/Group Description SYNT001 Dose 1: Participants received ALXN1830.
    Period Title: Overall Study
    STARTED 8
    Received at Least 1 Dose of Study Drug 8
    COMPLETED 7
    NOT COMPLETED 1

    Baseline Characteristics

    Arm/Group Title Cohort 1: ALXN1830
    Arm/Group Description SYNT001 Dose 1: Participants received ALXN1830.
    Overall Participants 8
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    54.9
    (16.82)
    Sex: Female, Male (Count of Participants)
    Female
    6
    75%
    Male
    2
    25%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    25%
    Not Hispanic or Latino
    6
    75%
    Unknown or Not Reported
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    Asian
    1
    12.5%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    Black or African American
    1
    12.5%
    White
    6
    75%
    More than one race
    0
    0%
    Unknown or Not Reported
    0
    0%
    Age at Warm Autoimmune Hemolytic Anemia Diagnosis (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    48.4
    (16.85)

    Outcome Measures

    1. Primary Outcome
    Title Count Of Participants Reporting Treatment-emergent Adverse Events (TEAEs)
    Description A TEAE was defined as any adverse event that starts on or after the first dose of study drug or occurs prior to the first dose and worsens in severity on or after the first dose of study drug, during the Treatment Period and Follow-up Period. A TEAE was considered "serious" if, in the view of either the investigator or sponsor, it resulted in any of the following outcomes: death, life-threatening adverse drug event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, congenital anomaly/birth defect, or an event that may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the previously listed outcomes. A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module. All serious TEAEs were not considered related to the study drug.
    Time Frame Day 0 (after first dose) through Day 112

    Outcome Measure Data

    Analysis Population Description
    Safety Population: All participants who received at least 1 dose of study drug.
    Arm/Group Title Cohort 1: ALXN1830
    Arm/Group Description SYNT001 Dose 1: Participants received ALXN1830.
    Measure Participants 8
    TEAEs
    8
    100%
    Serious TEAEs
    2
    25%
    Discontinuations due to TEAEs
    0
    0%
    Deaths
    0
    0%
    2. Secondary Outcome
    Title Maximum Serum Concentration (Cmax) On Day 0 And Day 28
    Description The Cmax was determined directly from the concentration-time profile. Starting on Days 0 and 28, serum samples were collected just prior to the start of study drug infusion (predose), at 5 minutes, at 2, 4, 6, 24, and 48 hours, and at 5 days postdose after the end-of-study drug infusion. Results are reported in micrograms/milliliter (ug/mL).
    Time Frame Predose, 5 minutes, 2, 4, 6, 24, and 48 hours, and 5 days postdose

    Outcome Measure Data

    Analysis Population Description
    PK Population: All participants who received at least 1 dose of study drug and had postdose PK data available at the specified timepoint.
    Arm/Group Title Cohort 1: ALXN1830
    Arm/Group Description SYNT001 Dose 1: Participants received ALXN1830.
    Measure Participants 8
    Day 0
    249.6
    (35.76)
    Day 28
    245.8
    (41.55)
    3. Secondary Outcome
    Title Change From Baseline In Reticulocyte Count At Day 33
    Description Reticulocyte count was measured as a PD biomarker. Pharmacodynamic samples were collected for analyses throughout the study prior to infusion of study drug for Cohort 1. Measurements for PD biomarkers were derived from the laboratory results. Results are reported in cells/liter (cells*10^12/L). A decrease in reticulocyte count indicated a potential improvement in condition.
    Time Frame Baseline, Day 33

    Outcome Measure Data

    Analysis Population Description
    PD Population: All participants who received at least 1 dose of study drug and had postdose PD data available at the specified timepoint.
    Arm/Group Title Cohort 1: ALXN1830
    Arm/Group Description SYNT001 Dose 1: Participants received ALXN1830.
    Measure Participants 7
    Mean (Standard Deviation) [cells*10^12/L]
    -0.044
    (0.0948)
    4. Secondary Outcome
    Title Change From Baseline In Hemoglobin At Day 33
    Description Hemoglobin was measured as a PD biomarker. Pharmacodynamic samples were collected for analyses throughout the study prior to infusion of study drug for Cohort 1. Measurements for PD biomarkers were derived from the laboratory results. Results are reported in grams/deciliter (g/dL). An increase in hemoglobin indicated a potential improvement in condition.
    Time Frame Baseline, Day 33

    Outcome Measure Data

    Analysis Population Description
    PD Population: All participants who received at least 1dose of study drug and had postdose PD data available at the specified timepoint.
    Arm/Group Title Cohort 1: ALXN1830
    Arm/Group Description SYNT001 Dose 1: Participants received ALXN1830.
    Measure Participants 8
    Mean (Standard Deviation) [g/dL]
    0.66
    (1.581)
    5. Secondary Outcome
    Title Immunogenicity Of ALXN1830 At Day 112, As Assessed By Anti-ALXN1830 Antibody Level
    Description Immunogenicity analyses are reported for Day 112. Testing was carried out to detect binding antidrug antibodies by anti-ALXN1830 antibody level. Results are reported as the reciprocal of the titer where they cross the study cut point.
    Time Frame Day 112

    Outcome Measure Data

    Analysis Population Description
    Safety Population: All participants who received at least 1 dose of study drug.
    Arm/Group Title Cohort 1: ALXN1830
    Arm/Group Description SYNT001 Dose 1: Participants received ALXN1830.
    Measure Participants 4
    Mean (Standard Deviation) [reciprocal of the titer]
    99.220
    (165.8149)

    Adverse Events

    Time Frame Baseline through Day 112
    Adverse Event Reporting Description
    Arm/Group Title Cohort 1: ALXN1830
    Arm/Group Description SYNT001 Dose 1: Participants received ALXN1830.
    All Cause Mortality
    Cohort 1: ALXN1830
    Affected / at Risk (%) # Events
    Total 0/8 (0%)
    Serious Adverse Events
    Cohort 1: ALXN1830
    Affected / at Risk (%) # Events
    Total 2/8 (25%)
    Blood and lymphatic system disorders
    Anaemia 1/8 (12.5%)
    Gastrointestinal disorders
    Gastritis 1/8 (12.5%)
    Other (Not Including Serious) Adverse Events
    Cohort 1: ALXN1830
    Affected / at Risk (%) # Events
    Total 8/8 (100%)
    Blood and lymphatic system disorders
    Anaemia 1/8 (12.5%)
    Thrombocytopenia 1/8 (12.5%)
    Cardiac disorders
    Sinus tachycardia 2/8 (25%)
    Eye disorders
    Blepharospasm 1/8 (12.5%)
    Gastrointestinal disorders
    Constipation 2/8 (25%)
    Nausea 2/8 (25%)
    Abdominal pain 1/8 (12.5%)
    General disorders
    Fatigue 2/8 (25%)
    Chills 1/8 (12.5%)
    Face oedema 1/8 (12.5%)
    Influenza like illness 1/8 (12.5%)
    Oedema peripheral 1/8 (12.5%)
    Pyrexia 1/8 (12.5%)
    Infections and infestations
    Pneumonia 1/8 (12.5%)
    Rhinitis 1/8 (12.5%)
    Upper respiratory tract infection 1/8 (12.5%)
    Urinary tract infection 1/8 (12.5%)
    Injury, poisoning and procedural complications
    Fall 1/8 (12.5%)
    Infusion-related reaction 1/8 (12.5%)
    Limb injury 1/8 (12.5%)
    Post-traumatic pain 1/8 (12.5%)
    Investigations
    Haematocrit decreased 1/8 (12.5%)
    Haemoglobin decreased 1/8 (12.5%)
    Metabolism and nutrition disorders
    Increased appetite 1/8 (12.5%)
    Musculoskeletal and connective tissue disorders
    Back pain 1/8 (12.5%)
    Muscle spasms 1/8 (12.5%)
    Nervous system disorders
    Headache 4/8 (50%)
    Dizziness 2/8 (25%)
    Dizziness postural 1/8 (12.5%)
    Hypersomnia 1/8 (12.5%)
    Syncope 1/8 (12.5%)
    Psychiatric disorders
    Restlessness 1/8 (12.5%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 2/8 (25%)
    Cough 1/8 (12.5%)
    Dyspnoea exertional 1/8 (12.5%)
    Skin and subcutaneous tissue disorders
    Dermatitis contact 1/8 (12.5%)
    Hyperhidrosis 1/8 (12.5%)
    Rash maculo-papular 1/8 (12.5%)
    Rash pruritic 1/8 (12.5%)
    Vascular disorders
    Flushing 1/8 (12.5%)

    Limitations/Caveats

    The study was terminated after the safety, tolerability, PK, PD, and efficacy were characterized in the Warm Autoimmune Hemolytic Anemia participants in Cohort 1 (SYNT001 Dose 1).

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Sponsor can review results communications at least 60 days prior to public release. Within 30 days of receipt, Sponsor shall advise of any information which is Confidential Information (other than Study Data) or which may impair the availability of patent protection for Inventions. Sponsor can require removal of specifically identified Confidential Information (other than Study Data) and/or delay the communication an additional 60 days to enable Sponsor to seek patent protection for Inventions.

    Results Point of Contact

    Name/Title Alexion Pharmaceuticals, Inc.
    Organization Alexion Pharmaceuticals, Inc.
    Phone 855-752-2356
    Email clinicaltrials@alexion.com
    Responsible Party:
    Alexion Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT03075878
    Other Study ID Numbers:
    • SYNT001-102
    First Posted:
    Mar 9, 2017
    Last Update Posted:
    May 13, 2020
    Last Verified:
    May 1, 2020