Assessment of Prolonged Safety and tOLerability of in Migraine Patients in a Long-term OpeN-label Study (APOLLON)

This is a 128-week open-label study to assess the long-term safety and tolerabilty of the monoclonal antibody erenumab in migraine patients.

Study Overview

• Status: Completed
• Conditions: Migraine; Migraine Disorders; Migraine Headache
• Intervention / Treatment: Biological: Erenumab

Detailed Description

This was an open-label, multi-center, single arm study with flexible dosing allowing both dose adjustment and one drug holiday per patient.

The study design consisted of 3 parts:

• Screening Epoch (0 - 2 weeks): required for all patients to assess initial eligibility. Eligible patients came from study CAMG334ADE01 (NCT03828539).
• Open-label Treatment Epoch (128 weeks): Individual patients were treated for 128 weeks. In this open-label treatment phase, the erenumab dose could be adjusted from 70 mg to 140 mg or vice versa at the discretion of the physician at any scheduled study visit. Additionally, a voluntary single treatment interruption ('drug holiday') of up to 24 weeks (approximately six months) could be introduced after at least 12 weeks of treatment in the open-label Treatment Epoch.
• Follow-up Epoch (4 weeks): A Follow-Up Visit 4 weeks after the last regular study visit (8 weeks after last investigational medicinal product [IMP] application) was required as part of routine safety monitoring.

• Study Type: Interventional
• Enrollment (Actual): 701
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Alzenau, Germany, 63755
    • Novartis Investigative Site
  • Bad Homburg, Germany, 61348
    • Novartis Investigative Site
  • Bad Honnef, Germany, 53604
    • Novartis Investigative Site
  • Bad Saarow, Germany, 15526
    • Novartis Investigative Site
  • Bayreuth, Germany, 95445
    • Novartis Investigative Site
  • Berlin, Germany, 10713
    • Novartis Investigative Site
  • Berlin, Germany, 14169
    • Novartis Investigative Site
  • Berlin, Germany, 13353
    • Novartis Investigative Site
  • Berlin, Germany, 120999
    • Novartis Investigative Site
  • Berlin, Germany, 12101
    • Novartis Investigative Site
  • Berlin, Germany, 12163
    • Novartis Investigative Site
  • Berlin, Germany, 12627
    • Novartis Investigative Site
  • Berlin, Germany, 13053
    • Novartis Investigative Site
  • Bielefeld, Germany, D 33647
    • Novartis Investigative Site
  • Boblingen, Germany, 71032
    • Novartis Investigative Site
  • Bochum, Germany, 44791
    • Novartis Investigative Site
  • Bonn, Germany, 53111
    • Novartis Investigative Site
  • Bonn, Germany, 53177
    • Novartis Investigative Site
  • Chemnitz, Germany, 09117
    • Novartis Investigative Site
  • Dillingen, Germany, 66763
    • Novartis Investigative Site
  • Erbach, Germany, 64711
    • Novartis Investigative Site
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Essen, Germany, 45133
    • Novartis Investigative Site
  • Frankfurt, Germany, 60313
    • Novartis Investigative Site
  • Freiburg, Germany, 79098
    • Novartis Investigative Site
  • Gelsenkirchen, Germany, 45879
    • Novartis Investigative Site
  • Greifswald, Germany, 17475
    • Novartis Investigative Site
  • Haar, Germany, 85540
    • Novartis Investigative Site
  • Halle, Germany, 06120
    • Novartis Investigative Site
  • Hamburg, Germany, 20253
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Hoppegarten, Germany, 15366
    • Novartis Investigative Site
  • Ibbenbueren, Germany, 49477
    • Novartis Investigative Site
  • Jena, Germany, 07740
    • Novartis Investigative Site
  • Juelich, Germany, 52428
    • Novartis Investigative Site
  • Kassel, Germany, 34121
    • Novartis Investigative Site
  • Kiel, Germany, 24149
    • Novartis Investigative Site
  • Koln, Germany, 50935
    • Novartis Investigative Site
  • Königstein im Taunus, Germany, 61462
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Leipzig, Germany, 04107
    • Novartis Investigative Site
  • Luenen, Germany, 44534
    • Novartis Investigative Site
  • Mannheim, Germany, 66163
    • Novartis Investigative Site
  • Marburg Wehrda, Germany, 35041
    • Novartis Investigative Site
  • Mittweida, Germany, 09648
    • Novartis Investigative Site
  • Muenchen, Germany, 81377
    • Novartis Investigative Site
  • Muenchen, Germany, 81675
    • Novartis Investigative Site
  • Muenster, Germany, 48149
    • Novartis Investigative Site
  • Neu-Ulm, Germany, 89231
    • Novartis Investigative Site
  • Neuburg an der Donau, Germany, 86633
    • Novartis Investigative Site
  • Osnabrück, Germany, 49074
    • Novartis Investigative Site
  • Pforzheim, Germany, 75172
    • Novartis Investigative Site
  • Quakenbrueck, Germany, 49610
    • Novartis Investigative Site
  • Regensburg, Germany, 93059
    • Novartis Investigative Site
  • Rostock, Germany, 18057
    • Novartis Investigative Site
  • Ruelzheim, Germany, 76761
    • Novartis Investigative Site
  • Schwerin, Germany, 19053
    • Novartis Investigative Site
  • Schwerin, Germany, 19055
    • Novartis Investigative Site
  • Seesen, Germany, 38723
    • Novartis Investigative Site
  • Siegen, Germany, 57076
    • Novartis Investigative Site
  • Sindelfingen, Germany, 71065
    • Novartis Investigative Site
  • Stadtroda, Germany, 07646
    • Novartis Investigative Site
  • Stuttgart, Germany, 70174
    • Novartis Investigative Site
  • Stuttgart, Germany, 70178
    • Novartis Investigative Site
  • Stuttgart, Germany, 70182
    • Novartis Investigative Site
  • Trier, Germany, 54292
    • Novartis Investigative Site
  • Tuebingen, Germany, 72076
    • Novartis Investigative Site
  • Ulm, Germany, 89073
    • Novartis Investigative Site
  • Unterhaching, Germany, 82008
    • Novartis Investigative Site
  • Westerstede Oldenburg, Germany, 26655
    • Novartis Investigative Site
  • Wiesbaden, Germany, 65191
    • Novartis Investigative Site
  • Wuerzburg, Germany, 97080
    • Novartis Investigative Site
  • Baden Wuertemberg
    • Stuttgart, Baden Wuertemberg, Germany, 70178
      • Novartis Investigative Site
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30159
      • Novartis Investigative Site
  • Nordrhein-Westfalen
    • Aachen, Nordrhein-Westfalen, Germany, 52062
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

The study population consisted of patients with a documented history of episodic (4 - 14 baseline migraine days) or chronic migraine (≥15 baseline headache days), who had been successfully randomized to clinical trial CAMG334ADE01.

Key inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study
• Patient is capable of understanding the nature, significance and implications of the clinical trial.
• Adults ≥18 years of age upon entry into screening

Key exclusion Criteria:

• Use of a prophylactic migraine medication within five plasma clearance half-lives, or a device or procedure within one month prior to the start of the Open-label Treatment Epoch. This exclusion criteria does not apply to erenumab or topiramate administered within clinical trial CAMG334ADE01
• Any prior exposure to (investigational) prophylactic migraine products targeting the CGRP pathway, other than erenumab.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Erenumab; Erenumab dose could be adjusted from 70 mg to 140 mg or vice versa at the discretion of the physician at any scheduled study visit.	Biological: Erenumab; Erenumab was supplied as a pre-filled pen (auto-injector) for subcutaneous injection.; Other Names: AMG334; Aimovig

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exposure Adjusted Incidence Rate of AE During Open-label Treatment Epoch Per 100 Subject Years	This outcome measure was calculated dividing the number of adverse events (AEs) by the total patient exposure time and standardizing it per 100 patient-years. Exact Pearson-Clopper confidence intervals for single proportions were calculated to evaluate the precision of the estimated parameter.	Up to 128 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients Discontinuing Open-label Treatment Epoch Due to AE	Participants discontinuing the Open-label Treatment Epoch due to adverse events (AEs) to evaluate the long-term tolerability of erenumab in patients with episodic migraine or chronic migraine.	Up to 128 weeks
Proportion of Patients Discontinuing Open-label Treatment Epoch Due to Non-AE Reasons	Participants discontinuing the Open-label Treatment Epoch due to non-AE reasons to evaluate the long-term tolerability of erenumab in patients with episodic migraine or chronic migraine.	Up to 128 weeks

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2019
• Primary Completion (Actual): February 23, 2023
• Study Completion (Actual): March 13, 2023

Study Registration Dates

• First Submitted: September 6, 2019
• First Submitted That Met QC Criteria: September 6, 2019
• First Posted (Actual): September 10, 2019

Study Record Updates

• Last Update Posted (Actual): February 6, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: monoclonal antibody; episodic migraine; chronic migraine; headache; migraine; erenumab; AMG334; aimovig; CGRP-receptor antibody
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Headache; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Calcitonin Gene-Related Peptide Receptor Antagonists; Erenumab
• Other Study ID Numbers: CAMG334ADE03; 2019-002201-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes