Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of ALXN1210 in Complement Inhibitor Treatment-Naïve Adult and Adolescent Participants With Atypical Hemolytic Uremic Syndrome (aHUS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02949128
Recruitment Status : Active, not recruiting
First Posted : October 31, 2016
Results First Posted : February 10, 2020
Last Update Posted : May 5, 2020
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Brief Summary:
The purpose of the study is to assess the safety and efficacy of ravulizumab to control disease activity in adolescent and adult participants with aHUS who had not previously used a complement inhibitor.

Condition or disease Intervention/treatment Phase
Atypical Hemolytic Uremic Syndrome (aHUS) Biological: Ravulizumab Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 58 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Single Arm Study of ALXN1210 in Complement Inhibitor Treatment-naïve Adult and Adolescent Patients With Atypical Hemolytic Uremic Syndrome (aHUS)
Actual Study Start Date : March 18, 2017
Actual Primary Completion Date : November 16, 2018
Estimated Study Completion Date : July 2023


Arm Intervention/treatment
Experimental: Ravulizumab

Participants were administered weight-based doses of ravulizumab every 8 weeks for 26 weeks in the Initial Evaluation Period.

After the Initial Evaluation Period, participants could enter an Extension Period and receive ravulizumab until the product registration or approval (in accordance with country-specific regulations) or for up to 4.5 years, whichever occurs first.

Biological: Ravulizumab
Single loading dose on Day 1, followed by regular maintenance dosing beginning on Day 15, based on weight: ≥ 40 to < 60 kilograms (kg), 2400 milligrams (mg) loading, then 3000 mg every 8 weeks; ≥ 60 to < 100 kg, 2700 mg loading, then 3300 mg every 8 weeks; ≥ 100 kg, 3000 mg loading, then 3600 mg every 8 weeks.
Other Names:
  • ALXN1210
  • Ultomiris




Primary Outcome Measures :
  1. Proportion Of Participants With Complete Thrombotic Microangiopathy (TMA) Response [ Time Frame: Week 26 ]
    Complete TMA response during the 26-week Initial Evaluation Period is a composite outcome measure that required normalization of hematological parameters (platelet count and lactate dehydrogenase [LDH]) and improvement in kidney function (≥25% reduction in serum creatinine from baseline); for participants on dialysis, baseline was established at least 6 days after the end of dialysis. Participants had to meet these criteria for 2 separate assessments obtained at least 4 weeks (28 days) apart, and any measurement in between. To be considered a responder during the 26-week Initial Evaluation Period, the latest time point a participant could first meet the response criteria was 28 days before the Week 26 (Day 183) assessment. Formal statistical comparison analyses were not planned for this study. The proportion was based on the responders among treated participants. The 95% confidence interval (CI) was based on the asymptotic Gaussian approximation method with a continuity correction.


Secondary Outcome Measures :
  1. Time To Complete TMA Response [ Time Frame: Baseline through Week 26 ]
    Participants that did not have a response were censored at the date of last visit or study discontinuation at the time when the analysis was performed. The time to complete TMA Response is reported in days. The time of the event of a confirmed complete TMA response was considered the first time point at which all the criteria for complete TMA response were met.

  2. Proportion Of Participants With Complete TMA Response At Week 26 [ Time Frame: Week 26 ]
    The proportion of participants considered responders, along with a 2-sided 95% CI for the Week 26 time point, is reported. To be considered a responder during the 26-week Initial Evaluation Period, the latest time point a participant could first meet the response criteria was 28 days before the Week 26 (Day 183) assessment (components of the response maintained for at least 28 days).

  3. Observed Value And Change From Baseline In Estimated Glomerular Filtration Rate (eGFR) At Week 26 [ Time Frame: Baseline, Week 26 ]
    Kidney function evaluated by eGFR was summarized at baseline and the Week 26 time point using descriptive statistics for continuous variables for the observed value, as well as the change from baseline. The baseline value was defined as the average of the values from the assessments performed prior to the first study drug infusion (these could include results from Screening and the Day 1 visit). A value of 10 milliliters (mL)/minute (min)/1.73 meters squared (m^2) for eGFR was imputed for participants requiring dialysis for acute kidney injury. The observed value and change from baseline are reported in mL/min/1.73 m^2. An increase indicated improvement in kidney function.

  4. Proportion Of Participants With Change From Baseline In Chronic Kidney Disease (CKD) Stage At Week 26 [ Time Frame: Baseline, Week 26 ]
    The CKD stage is presented as the change from baseline in the proportion of participants that Improved (excluding those with Stage 1 [normal renal function] at baseline as they cannot improve), Worsened (excluding those with Stage 5 at baseline as they cannot worsen), and Stayed the Same, compared to the CKD stage at baseline. Baseline was derived based on the last available eGFR before starting treatment. Stage 5 was considered the worst category, while Stage 1 was considered the best category. A 2-sided 95% CI for the proportion, based on exact confidence limits using the Clopper-Pearson method, was provided for each category. The CKD stage was classified based on the National Kidney Foundation Chronic Kidney Disease Stage.

  5. Change From Baseline In Platelet Count At Week 26 [ Time Frame: Baseline, Week 26 ]
    The hematologic TMA parameter of platelet count was summarized at baseline and at Week 26 using descriptive statistics for continuous variables for the change from baseline. Results are reported in platelets*10^9/liter (L) blood.

  6. Change From Baseline In LDH At Week 26 [ Time Frame: Baseline, Week 26 ]
    The hematologic TMA parameter of serum LDH was summarized at baseline and at Week 26 using descriptive statistics for continuous variables for the change from baseline. Results are reported in units (U)/L.

  7. Change From Baseline In Hemoglobin At Week 26 [ Time Frame: Baseline, Week 26 ]
    The hematologic TMA parameter of hemoglobin level was summarized at baseline and at Week 26 using descriptive statistics for continuous variables for the change from baseline. Results are reported in grams (g)/L.

  8. Proportion Of Participants With An Increase From Baseline In Hemoglobin ≥ 20 g/L Through Week 26 [ Time Frame: Up to Week 26 ]
    The proportion of participants with an increase from baseline in hemoglobin ≥ 20 g/L, observed at 2 separate assessments obtained at least 4 weeks (28 days) apart, and any measurement in between, was assessed through Week 26 and is presented as the proportion of responders, along with a 2-sided 95% CI. The 95% CIs are based on the asymptotic Gaussian approximation method with a continuity correction. To be considered a responder during the 26-week Initial Evaluation Period, the latest time point a participant could first meet the response criteria was 28 days before the Week 26 (Day 183) assessment (components of the response maintained for at least 28 days).

  9. Change From Baseline In Quality Of Life As Measured By The EuroQol 5-Dimension 3-Level (EQ-5D-3L) At Week 26 [ Time Frame: Baseline, Week 26 ]
    The EQ-5D-3L is a participant-answered questionnaire that scores 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression (scored as a 1, 2, or 3, with 3 being the worst health state), as well as health state on a visual analogue scale (0 to 100, with 100 representing the best health state). From these scores, a summary index score is derived using the time trade-off valuation set for the United States and ranges from -1 to 1, where a score above 0.94 indicates full health. An increase in score from baseline indicates improvement in quality of life.

  10. Change From Baseline In Quality Of Life As Measured By The Functional Assessment Of Chronic Illness Therapy (FACIT)-Fatigue Version 4 Questionnaire At Week 26 [ Time Frame: Baseline, Week 26 ]
    Quality of life was evaluated in part using FACIT Fatigue Version 4. The data were summarized at baseline and at the Week 26 time point using descriptive statistics for continuous variables. The FACIT Fatigue Version 4 questionnaire at baseline and the Week 26 timepoint was scored using standard scoring algorithms. The score ranges from 0-52, with a higher score indicating less Fatigue. An increase in score indicated an improvement in quality of life.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female ≥ 12 years of age and weighing ≥ 40 kg at the time of consent.
  2. Evidence of thrombotic microangiopathy, including low platelet count, hemolysis (breaking of red blood cells inside of blood vessels), and decreased kidney function.
  3. Documented meningococcal vaccination not more than 3 years prior to, or at the time of, initiating study drug. Participants who received a meningococcal vaccine less than 2 weeks before initiating ravulizumab treatment must have received treatment with appropriate prophylactic antibiotics until 2 weeks after vaccination. Participants who had not been vaccinated prior to initiating ravulizumab treatment should have received prophylactic antibiotics prior to and for at least 2 weeks after meningococcal vaccination. Participants < 18 years of age must have been vaccinated against haemophilus influenzae type b and streptococcus pneumoniae according to national and local vaccination schedule guidelines.
  4. Female participants of childbearing potential and male participants with female partners of childbearing potential had to use highly effective contraception starting at screening and continuing until at least 8 months after the last dose of ravulizumab.

Exclusion Criteria:

  1. A disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 deficiency (activity < 5%).
  2. Shiga toxin-related hemolytic uremic syndrome.
  3. Positive direct Coombs test.
  4. Pregnancy or breastfeeding.
  5. Identified drug exposure-related hemolytic uremic syndrome (HUS).
  6. Bone marrow transplant/hematopoietic stem cell transplant within last 6 months prior to start of Screening.
  7. HUS related to known genetic defects of cobalamin C metabolism.
  8. Systemic sclerosis (scleroderma), systemic lupus erythematosus, or antiphospholipid antibody positivity or syndrome.
  9. Chronic dialysis (defined as dialysis on a regular basis as renal replacement therapy for end-stage kidney disease).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02949128


Locations
Layout table for location information
United States, Indiana
Clinical Trial Site
Fort Wayne, Indiana, United States, 46804
Clinical Trial Site
Fort Wayne, Indiana, United States, 46845
United States, North Carolina
Clinical Trial Site
Durham, North Carolina, United States, 27705
Clinical Trial Site
Winston-Salem, North Carolina, United States, 27103
United States, Ohio
Clinical Trial Site
Columbus, Ohio, United States, 43210
Australia
Clinical Trial Site
Clayton, Australia
Clinical Trial Site
Geelong, Australia
Clinical Trial Site
Parkville, Australia
Austria
Clinical Trial Site
Vienna, Austria
Belgium
Clinical Trial Site
Brussels, Belgium
Canada
Clinical Trial Site
London, Canada
France
Clinical Trial Site
Bordeaux, France
Clinical Trial Site
Clermont-Ferrand, France
Clinical Trial Site
Lille, France
Clinical Trial Site
Montpellier, France
Clinical Trial Site
Nice, France
Clinical Trial Site
Paris, France
Germany
Clinical Trial Site
Aachen, Germany
Clinical Trial Site
Essen, Germany
Clinical Trial Site
Hanover, Germany
Clinical Trial Site
Muenchen, Germany
Clinical Trial Site
Tuebingen, Germany
Italy
Clinical Trial Site
Bologna, Italy
Clinical Trial Site
Firenze, Italy
Japan
Clinical Trial Site
Saitama, Japan
Clinical Trial Site
Tokyo, Japan
Korea, Republic of
Clinical Trial Site
Gyeonggi-do, Korea, Republic of
Clinical Trial Site
Seoul, Korea, Republic of
Russian Federation
Clinical Trial Site
Moscow, Russian Federation
Clinical Trial Site
Saint Petersburg, Russian Federation
Spain
Clinical Trial Site
Barcelona, Spain
Clinical Trial Site
Madrid, Spain
Clinical Trial Site
Valencia, Spain
Taiwan
Clinical Trial Site
Taichung, Taiwan
Clinical Trial Site
Taipei City, Taiwan
Clinical Trial Site
Taipei, Taiwan
United Kingdom
Clinical Trial Site
Cardiff, United Kingdom
Clinical Trial Site
London, United Kingdom
Sponsors and Collaborators
Alexion Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Alexion Pharmaceuticals:
Study Protocol  [PDF] May 7, 2019
Statistical Analysis Plan  [PDF] September 15, 2017


Layout table for additonal information
Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02949128    
Other Study ID Numbers: ALXN1210-aHUS-311
2016‐002027‐29 ( EudraCT Number )
First Posted: October 31, 2016    Key Record Dates
Results First Posted: February 10, 2020
Last Update Posted: May 5, 2020
Last Verified: February 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Azotemia
Hemolytic-Uremic Syndrome
Atypical Hemolytic Uremic Syndrome
Syndrome
Hemolysis
Disease
Pathologic Processes
Uremia
Kidney Diseases
Urologic Diseases
Anemia, Hemolytic
Anemia
Hematologic Diseases
Thrombotic Microangiopathies
Thrombocytopenia
Blood Platelet Disorders
Ravulizumab
Complement Inactivating Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs