Study to Evaluate the Safety and Efficacy of GSK1278863 in Recombinant Human Erythropoietin (rhEPO) Hyporesponsive Hemodialysis-dependent Chronic Kidney Disease Subjects With Anemia

NCT02075463 | Terminated Phase 2 Results DMC

• 1 other identifier: 114837
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 19

Brief Summary

The study will evaluate the ability of GSK1278863 to increase the hemoglobin (Hgb) concentration, or maintain it within the target range, and the safety and efficacy of GSK1278863 over 16 weeks of treatment, in hemodialysis-dependent subjects with anemia associated with chronic kidney disease who are chronically hyporesponsive to rhEPO. The data generated will inform dose requirements for any chronic rhEPO hyporesponsive hemodialysis-dependent subjects included in future clinical trials. The study consists of a 4-week rhEPO run-in period, a 16-week GSK1278863 treatment period and a 4-week Follow-up period.

Conditions

Anemia

Keywords

recombinant human erythropoietin; GSK1278863; hemodialysis; anemia; Hemoglobin; chronic rhEPO hyporesponsiveness; chronic kidney disease; erythropoiesis stimulating agents; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Demonstrating an Increase in Hgb of >=1 g/dL (if Baseline Hgb is <9.5 g/dL), or >=0.5 g/dL (if Baseline Hgb is 9.5-<10 g/dL), or Stay Within Target Range and do Not Drop by >0.5 g/dL (if Baseline Hgb is >= 10 g/dL) at Week 16

  Percentage of participants with increased Hgb \>=1 g/dL (if baseline Hgb is \<9.5 g/dL), or \>=0.5 g/dL (if baseline Hgb is 9.5-\<10 g/dL), or within the target range and not dropped by \>0.5 g/dL (if baseline Hgb is \>= 10 g/dL) at Week 16 are presented. Participants who were available at the indicated time point were analyzed

  Week 16

Secondary Outcomes (21)

• Change From Baseline in Hgb Levels at Week 16

  Week 16

• Percentage of Time (Days) Hgb Levels Within, Below and Above Target Range at the Indicated Time Point

  Week 12 to Week 16

• Number of Participants Achieving at Least 1 g/dL Increase in Hgb From Baseline at Week 16

  Baseline and Week 16

• Number of Participants With Hgb in the Target Range at Week 16

  Week 16

• Number of Participants Reaching Pre-defined Hgb Stopping Criteria

  Up to Week 16

Study Arms (1)

GSK1278863 Arm

EXPERIMENTAL

Subjects will receive a fixed starting dose of 12 milligrams (mg) GSK1278863 once daily (QD) orally for first 4 weeks. From Week 4 the dose of GSK1278863 will be adjusted based on Hgb levels and evaluated every 4 weeks until Week 16. This starting dose may be changed during the study if there is an early indication of either lack of efficacy or the rate of rise in Hgb is too rapid

Drug: GSK1278863; Drug: Placebo

Interventions

GSK1278863 DRUG

Film coated tablets containing 1 mg, 2 mg, 5 mg or 25 mg of GSK1278863

GSK1278863 Arm

Placebo DRUG

Matching placebo tablet for GSK1278863

GSK1278863 Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hemodialysis (HD) frequency: Stable HD regimen of three to four times weekly for a minimum of 12 weeks. Note: The type and frequency of dialysis must be stable during the study. Isolated ultrafiltration sessions for the purposes of fluid removal are permitted.
• Dialysis Adequacy: Single-pool dialyzer clearance multiplied by dialyzer time divided by volume of distribution of urea (Kt/Vurea) of \>=1.2 based on a historical value obtained within the prior month.
• rhEPO hyporesponsiveness: Historical and current intravenous (IV) rhEPO and Hgb values. Average epoetin alfa dose and Hgb level for three 4-week periods for a total of 12 weeks prior to Week -4, and during the 4 week run-in period, must be within the following ranges: average epoetin alfa dose \>4000 and \<=6000 units per session and Hgb \>=8.0 and \<=9.5 g/dL; average epoetin alfa dose \>6000 and \<=8000 units per session and Hgb \>=8.0 and \<=10.0 g/dL; average epoetin alfa dose \>8000 and \<=10000 units per session and Hgb \>=8.0 and \<=10.5 g/dL; and average epoetin alfa dose \>10000 units per session and Hgb \>=8.0 and \<=11.0 g/dL.
• Absolute difference between the Hgb value at Week -4 and Week 0 (Day 1), must be \<1.3 g/dL. Note: Subjects who do not meet the criteria after being rescreened twice, should not be entered into the GSK1278863 treatment period and should be withdrawn from the study.
• Age: \>=18 years of age.
• Gender: Female and male subjects. Females: If of childbearing potential, must agree to use one of the approved contraception methods from Screening until completion of the Follow-up Visit OR, of non-childbearing potential defined as pre-menopausal females with a documented tubal ligation, hysterectomy or oophorectomy; or postmenopausal defined as 12 months of spontaneous amenorrea \[in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) 23.0-116.3 milliinternational units (MIU)/milliliter (mL) (23.0-116.3 international units (IU)/liter (L)) and estradiol \<=10 picograms (pg)/mL (\<=37 picomole (pmol)/L) is confirmatory\]. Females on hormone replacement therapy (HRT) whose menopausal status is in doubt will be required to use one of the approved contraception methods if they wish to continue their HRT during the study. Otherwise they must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study without use of a contraceptive method.

You may not qualify if:

• Dialysis modality: Planned change in dialysis modality within the study time period.
• rhEPO: Use of methoxy polyethylene glycol epoetin beta or darbepoetin within the prior 8 weeks prior to Week -4.
• Renal transplant: Scheduled renal transplant.
• Transferrin saturation (TSAT): \<20% on the most recent sample taken over the last 12 weeks.
• Ferritin: \<100 nanograms (ng)/mL (\<100 micrograms/L) on the most recent sample taken over the last 12 weeks.
• Vitamin B12: At or below the lower limit of the reference range (may rescreen in a minimum of 8 weeks).
• Folate: \<2.0 ng/mL (\<4.5 nanomoles (nmol)/L) (may rescreen in a minimum of 4 weeks).
• Myocardial infarction or acute coronary syndrome: Within the 8 weeks prior to Week -4.
• Stroke or transient ischemic attacks (TIAs): Within the 8 weeks prior to Week -4.
• Heart failure: Class III/IV heart failure, as defined by the New York Heart Association (NYHA) functional classification system diagnosed prior to Week -4.
• Hypertension: Defined using pre-dialysis vitals (Week -4) of diastolic blood pressure \>100 millimeters of mercury (mmHg) or systolic blood pressure \>170 mmHg.
• Thrombotic disease: History of thrombotic disease (e.g., venous thrombosis such as deep vein thrombosis or pulmonary embolism, or arterial thrombosis such as new onset or worsening limb ischemia requiring intervention) within the 8 weeks prior to Week -4, except vascular access thrombosis.
• Inflammatory disease: Active chronic inflammatory disease that could impact erythropoiesis (e.g., scleroderma, systemic lupus erythematosis, rheumatoid arthritis, celiac disease) diagnosed prior to Week -4.
• Hematological disease: Any hematological disease including those affecting platelets, white or red blood cells (e.g., antibody-mediated pure red cell aplasia, sickle cell anemia, myelodysplastic syndromes, hematological malignancy, myeloma, hemolytic anemia), coagulation disorders (e.g., antiphospholipid syndrome, Protein C or S deficiency), or any other cause of anemia other than renal disease diagnosed prior to Week -4.
• Major surgery: (excluding vascular access surgery) within the 8 weeks prior to Week -4, or planned during the study.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (19)

GSK Investigational Site

Azusa, California, 91702, United States

Location

GSK Investigational Site

Glendale, California, 91204, United States

Location

GSK Investigational Site

Los Angeles, California, 90022, United States

Location

GSK Investigational Site

Los Angeles, California, 90025, United States

Location

GSK Investigational Site

Paramount, California, 90723, United States

Location

GSK Investigational Site

San Diego, California, 92115, United States

Location

GSK Investigational Site

Simi Valley, California, 93065, United States

Location

GSK Investigational Site

Middlebury, Connecticut, 06762, United States

Location

GSK Investigational Site

Hollywood, Florida, 33024, United States

Location

GSK Investigational Site

Tampa, Florida, 33609, United States

Location

GSK Investigational Site

Macon, Georgia, 31217, United States

Location

GSK Investigational Site

Southgate, Michigan, 48195, United States

Location

GSK Investigational Site

Saint Ann, Missouri, 63074, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

Amherst, New York, 14226, United States

Location

GSK Investigational Site

Asheville, North Carolina, 28801, United States

Location

GSK Investigational Site

Bethlehem, Pennsylvania, 18017, United States

Location

GSK Investigational Site

Knoxville, Tennessee, 37923, United States

Location

GSK Investigational Site

Houston, Texas, 77004, United States

Location

MeSH Terms

Conditions

Anemia; Renal Insufficiency, Chronic

Interventions

GSK1278863

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Due to the study terminating early, resulting in a sparse amount of data, selected parameters were not summarized.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2014
• First Posted: March 3, 2014
• Study Start: June 1, 2014
• Primary Completion: March 1, 2016
• Study Completion: March 16, 2016
• Last Updated: June 21, 2017
• Results First Posted: June 21, 2017

Record last verified: 2017-04

Locations

US (19)