Head-to-Head Study of Etelcalcetide (AMG 416) and Cinacalcet

NCT01896232 | Completed Phase 3 Results DMC

• 2 other identifiers: 201203602013-000192-33
• Study Type: interventional
• Target: 683
• Locations: 21 countries
• Sites: 179

Brief Summary

The purpose of this study is to demonstrate that treatment with etelcalcetide (AMG 416) is not inferior to treatment with cinacalcet for lowering serum parathyroid hormone (PTH) levels by \> 30% from baseline among patients with chronic kidney disease (CKD) and secondary hyperparathyroidism (SHPT) who require management with hemodialysis.

Conditions

Secondary Hyperparathyroidism; Chronic Kidney Disease

Keywords

Secondary Hyperparathyroidism, renal, kidney, kidneys, dialysis, hemodialysis, chronic kidney disease, CKD, SHPT

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With > 30% Reduction From Baseline in Mean Parathyroid Hormone During the Efficacy Assessment Phase - Non-inferiority Analysis

  Baseline and the efficacy assessment phase (EAP; defined as Weeks 20 to 27, inclusive).

Secondary Outcomes (7)

• Percentage of Participants With > 50% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase

  Baseline and the efficacy assessment phase (Weeks 20 to 27, inclusive).

• Percentage of Participants With > 30% Reduction From Baseline in Mean PTH During the Efficacy Assessment Phase

  Baseline and the efficacy assessment phase (Week 20 to Week 27)

• Mean Number of Days of Vomiting or Nausea Per Week in the First 8 Weeks

  First 8 weeks

• Percent Change From Baseline in Mean Corrected Calcium During the Efficacy Assessment Phase

  Baseline and the efficacy assessment phase (weeks 20 - 27)

• Percentage of Participants With Mean Predialysis Serum Phosphorus ≤ 4.5 mg/dL During the Efficacy Assessment Phase

  Efficacy assessment phase (weeks 20 - 27)

Study Arms (2)

Cinacalcet

ACTIVE COMPARATOR

Participants were randomized to receive oral cinacalcet once daily and placebo intravenous bolus injection at the end of each hemodialysis session, three times per week (TIW) for 26 weeks. The starting dose of cinacalcet was 30 mg daily and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining corrected calcium (cCa) ≥ 8.3 mg/dL.

Drug: Cinacalcet; Drug: Intravenous Placebo

Etelcalcetide

EXPERIMENTAL

Participants were randomized to receive etelcalcetide administered by intravenous bolus injection at the end of each hemodialysis session TIW, and daily oral doses of placebo tablets for 26 weeks. The starting dose of etelcalcetide was 5 mg, and could have been titrated at weeks 5, 9, 13, and 17 to target predialysis serum PTH ≤ 300 pg/mL but no lower than 100 pg/mL while maintaining cCa ≥ 8.3 mg/dL.

Drug: Etelcalcetide; Drug: Oral Placebo

Interventions

Etelcalcetide DRUG

Administered intravenously three times per week. The starting dose was 5 mg, titrated up to 15 mg based on serum PTH and corrected calcium levels.

Also known as: AMG 416

Etelcalcetide

Cinacalcet DRUG

Cinacalcet was administered orally once a day. The starting dose was 30 mg daily, titrated up to 180 mg daily based on serum PTH and corrected calcium levels.

Also known as: Sensipar®, Mimpara®

Cinacalcet

Oral Placebo DRUG

Administered orally once a day.

Etelcalcetide

Intravenous Placebo DRUG

Administered intravenously (IV) three times per week.

Cinacalcet

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Eligible subjects must be receiving adequate thrice weekly maintenance hemodialysis with a dialysate calcium concentration ≥ 2.5 mEq/L for at least 3 months prior to screening laboratory assessments
• Subjects must have SHPT as defined by one central laboratory screening predialysis serum PTH value \> 500 pg/mL, measured on separate days within 2 weeks prior to randomization
• Subjects must have one serum cCa value ≥ 8.3 mg/dL obtained before dialysis within 2 weeks of the date of randomization
• Subjects receiving calcium supplements must have no more than a maximum dose change of 50% within 2 weeks before screening laboratory assessments are obtained, and the dose must remain unchanged through randomization

You may not qualify if:

• Eligible subjects cannot have received cinacalcet during the 3 months preceding the first screening laboratory assessment
• Other criteria may apply

Sponsors & Collaborators

• Amgen: lead

Study Sites (182)

Research Site

Azusa, California, 91702, United States

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Bakersfield, California, 93306, United States

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Bakersfield, California, 93309, United States

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Chula Vista, California, 91910, United States

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Covina, California, 91723, United States

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Granada Hills, California, 91344, United States

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La Mesa, California, 91942, United States

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La Puente, California, 91744, United States

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Los Angeles, California, 90022, United States

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San Diego, California, 92123, United States

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San Gabriel, California, 91776, United States

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Whittier, California, 90603, United States

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Arvada, Colorado, 80002, United States

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Aurora, Colorado, 80045, United States

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Longmont, Colorado, 80501, United States

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Westminster, Colorado, 80031, United States

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Orange, Connecticut, 06477, United States

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Pembroke Pines, Florida, 33028, United States

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Pinecrest, Florida, 33156, United States

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Tampa, Florida, 33614, United States

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Baton Rouge, Louisiana, 70808, United States

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Lafayette, Louisiana, 70501, United States

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Southgate, Michigan, 48195, United States

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Columbus, Mississippi, 39705, United States

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Gulfport, Mississippi, 39501, United States

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Sewell, New Jersey, 08080, United States

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Great Neck, New York, 11021, United States

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Mineola, New York, 11501, United States

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Ridgewood, New York, 11385, United States

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Rosedale, New York, 11422, United States

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The Bronx, New York, 10461, United States

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Wilmington, North Carolina, 28401, United States

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Cincinnati, Ohio, 45206, United States

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Columbus, Ohio, 43215, United States

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Philadelphia, Pennsylvania, 19106, United States

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Houston, Texas, 77030, United States

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San Antonio, Texas, 78229, United States

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Burlington, Vermont, 05401, United States

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Fairfax, Virginia, 22033, United States

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Portsmouth, Virginia, 23704, United States

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Madison, Wisconsin, 53713, United States

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Feldkirch, 6807, Austria

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Linz, 4010, Austria

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Vienna, 1220, Austria

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Genk, 3600, Belgium

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Hasselt, 3500, Belgium

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Kortrijk, 8500, Belgium

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Roeselare, 8800, Belgium

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Edmonton, Alberta, T6G 2B7, Canada

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Saint John, New Brunswick, E2L 4L2, Canada

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St. John's, Newfoundland and Labrador, A1B 3V6, Canada

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Brampton, Ontario, L6R 3J7, Canada

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Greenfield Park, Quebec, J4V 2H1, Canada

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Nový Jičín, 741 01, Czechia

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Prague, 169 00, Czechia

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Praha 4 - Nusle, 140 00, Czechia

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Slavkov u Brna, 684 01, Czechia

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Třinec, 739 61, Czechia

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Ústí nad Orlicí, 562 18, Czechia

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Aalborg, 9000, Denmark

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Copenhagen, 2100, Denmark

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Fredericia, 7000, Denmark

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Odense, 5000, Denmark

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Roskilde, 4000, Denmark

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Tallinn, 10617, Estonia

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Tallinn, 13419, Estonia

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Tartu, 51014, Estonia

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Boulogne-sur-Mer, 62200, France

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Lille, 59800, France

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Nouilly, 57645, France

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Paris, 75011, France

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Paris, 75014, France

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Saint-Ouen, 93400, France

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Saint-Priest-en-Jarez, 42270, France

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Sainte-Foy-lès-Lyon, 66046, France

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Aachen, 52074, Germany

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Coburg, 96450, Germany

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Hamburg, 22297, Germany

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Hanover, 30625, Germany

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Magdeburg, 39120, Germany

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Mettmann, 40822, Germany

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Minden, 32429, Germany

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München, 81675, Germany

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Wiesbaden, 65191, Germany

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Zwickau, 08060, Germany

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Alexandroupoli, 68100, Greece

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Athens, 11528, Greece

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Ioannina, 45500, Greece

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Larissa, 41110, Greece

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Nikaia, Piraeus, 18454, Greece

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Pátrai, 26500, Greece

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Thessaloniki, 54636, Greece

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Budapest, 1115, Hungary

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Győr, 9023, Hungary

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Kaposvár, 7400, Hungary

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Kistarcsa, 2143, Hungary

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Pécs, 7624, Hungary

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Pécs, 7633, Hungary

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Székesfehérvár, 8000, Hungary

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Szigetvár, 7900, Hungary

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Zalaegerszeg, 8900, Hungary

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Cagliari, 09134, Italy

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Florence, 50139, Italy

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Genova, 16132, Italy

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Lecco, 23900, Italy

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Lucca, 55100, Italy

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Milan, 20122, Italy

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Pavia, 27100, Italy

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Pisa, 56126, Italy

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Pordenone, 33170, Italy

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San Giovanni Rotondo FG, 71013, Italy

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Riga, 1001, Latvia

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Riga, 1038, Latvia

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Valmiera, 4201, Latvia

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Alytus, 63351, Lithuania

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Kaunas, 50009, Lithuania

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Kaunas, 50169, Lithuania

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Kėdainiai, 57164, Lithuania

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Klaipėda, LT-93220, Lithuania

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Šiauliai, 76299, Lithuania

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Ukmerge, 20184, Lithuania

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Hamilton, 3240, New Zealand

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Papatoetoe, Auckland, 2025, New Zealand

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Takapuna, Auckland City, 0622, New Zealand

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Gdansk, 80-104, Poland

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Katowice, 40-027, Poland

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Poznan, 60-355, Poland

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Poznan, 61-696, Poland

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Sieradz, 98-200, Poland

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Wadowice, 34-100, Poland

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Warsaw, 01-211, Poland

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Warsaw, 02-507, Poland

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Zabrze, 41-800, Poland

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Żyrardów, 96-300, Poland

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Almada, 2800-455, Portugal

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Aveiro, 3800-266, Portugal

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Estoril, 2765-294, Portugal

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Forte Da Casa, 2625-437, Portugal

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Guimarães, 4810-273, Portugal

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Lisbon, 1750-130, Portugal

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Santo Tirso, 4780-383, Portugal

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Setúbal, 2900-655, Portugal

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Vila Franca de Xira, 2600-076, Portugal

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Mitishi, 141009, Russia

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Moscow, 123182, Russia

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Moscow, 129327, Russia

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Petrozavodsk, 185019, Russia

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Saint Petersburg, 191104, Russia

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Saint Petersburg, 193318, Russia

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Saint Petersburg, 195067, Russia

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Saint Petersburg, 197110, Russia

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Saint Petersburg, 198510, Russia

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Yaroslavl, 150062, Russia

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Córdoba, Andalusia, 14004, Spain

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Puerto Real, Andalusia, 11510, Spain

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Galdakao, Basque Country, 48960, Spain

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Badalona, Catalonia, 08916, Spain

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Lleida, Catalonia, 25198, Spain

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Badajoz, Extremadura, 06080, Spain

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Pamplona, Navarre, 31008, Spain

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Torrevieja, Valencia, 03186, Spain

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Valencia, Valencia, 46017, Spain

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Madrid, 28007, Spain

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Madrid, 28040, Spain

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Malmo, 205 02, Sweden

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Stockholm, 118 67, Sweden

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Trollhättan, 467 85, Sweden

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Aarau, 5001, Switzerland

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Bern, 3010, Switzerland

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Geneva, 1211, Switzerland

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Lausanne, 1003, Switzerland

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Lausanne, 1011, Switzerland

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Locarno, 6600, Switzerland

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Zurich, 8091, Switzerland

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Ankara, 06230, Turkey (Türkiye)

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Ankara, 06500, Turkey (Türkiye)

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Ankara, 06810, Turkey (Türkiye)

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Istanbul, 34371, Turkey (Türkiye)

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Istanbul, 34890, Turkey (Türkiye)

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Izmir, 35100, Turkey (Türkiye)

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Izmir, 35340, Turkey (Türkiye)

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Izmir, 35360, Turkey (Türkiye)

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Related Publications (6)

• Block GA, Bushinsky DA, Cheng S, Cunningham J, Dehmel B, Drueke TB, Ketteler M, Kewalramani R, Martin KJ, Moe SM, Patel UD, Silver J, Sun Y, Wang H, Chertow GM. Effect of Etelcalcetide vs Cinacalcet on Serum Parathyroid Hormone in Patients Receiving Hemodialysis With Secondary Hyperparathyroidism: A Randomized Clinical Trial. JAMA. 2017 Jan 10;317(2):156-164. doi: 10.1001/jama.2016.19468.

  PMID: 28097356 BACKGROUND

• Stollenwerk B, Iannazzo S, Akehurst R, Adena M, Briggs A, Dehmel B, Parfrey P, Belozeroff V. A Decision-Analytic Model to Assess the Cost-Effectiveness of Etelcalcetide vs. Cinacalcet. Pharmacoeconomics. 2018 May;36(5):603-612. doi: 10.1007/s40273-017-0605-2.

  PMID: 29392552 BACKGROUND

• Stollenwerk B, Iannazzo S, Cooper K, Belozeroff V. Exploring the potential value of improved care for secondary hyperparathyroidism with a novel calcimimetic therapy. J Med Econ. 2017 Oct;20(10):1110-1115. doi: 10.1080/13696998.2017.1360309. Epub 2017 Aug 14.

  PMID: 28803497 BACKGROUND

• Wu B, Melhem M, Subramanian R, Chen P, Jaramilla Sloey B, Fouqueray B, Hock MB, Skiles GL, Chow AT, Lee E. Clinical Pharmacokinetics and Pharmacodynamics of Etelcalcetide, a Novel Calcimimetic for Treatment of Secondary Hyperparathyroidism in Patients With Chronic Kidney Disease on Hemodialysis. J Clin Pharmacol. 2018 Jun;58(6):717-726. doi: 10.1002/jcph.1090. Epub 2018 Mar 13.

  PMID: 29534286 BACKGROUND

• Block GA, Chertow GM, Sullivan JT, Deng H, Mather O, Tomlin H, Serenko M. An integrated analysis of safety and tolerability of etelcalcetide in patients receiving hemodialysis with secondary hyperparathyroidism. PLoS One. 2019 Mar 15;14(3):e0213774. doi: 10.1371/journal.pone.0213774. eCollection 2019.

  PMID: 30875390 BACKGROUND

• Wolf M, Block GA, Chertow GM, Cooper K, Fouqueray B, Moe SM, Sun Y, Tomlin H, Vervloet M, Oberbauer R. Effects of etelcalcetide on fibroblast growth factor 23 in patients with secondary hyperparathyroidism receiving hemodialysis. Clin Kidney J. 2019 Apr 26;13(1):75-84. doi: 10.1093/ckj/sfz034. eCollection 2020 Feb.

  PMID: 32082556 BACKGROUND

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Hyperparathyroidism, Secondary; Renal Insufficiency, Chronic

Interventions

etelcalcetide hydrochloride; Cinacalcet

Condition Hierarchy (Ancestors)

Hyperparathyroidism; Parathyroid Diseases; Endocrine System 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

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2013
• First Posted: July 11, 2013
• Study Start: August 13, 2013
• Primary Completion: November 12, 2014
• Study Completion: January 8, 2015
• Last Updated: July 18, 2019
• Results First Posted: February 8, 2017

Record last verified: 2019-07

Locations

CH (7); US (41); HU (9); AU (3); DE (10); CA (5); LI (7); BE (4); ES (11); GR (7); FR (8); PL (10); PT (9); RU (10); SE (3); DK (5); TU (8); LA (3); CZ (6); NZ (3); IT (10)