Double-Blind Comparison of the Efficacy and Safety of C213 to Placebo for the Acute Treatment of Cluster Headaches

NCT04066023 | Completed Phase 2 Results FDA Drug

• 1 other identifier: CP-2019-001
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 12

Brief Summary

This is a double-blind, placebo-controlled study. Subjects who meet the entry criteria will be randomized o receive one of three blinded treatments \[C213 1.9 mg patch and placebo patch; C213 3.8 mg (1.9 mg x 2 patches), two placebo patches\] on Day 1 and will have up to 48 weeks to confirm and treat a cluster headache. Subjects will self-administer the patches and respond to questions in the electronic diary (eDiary) until 1-hour post treatment administration.

Conditions

Cluster Headache

Keywords

Episodic cluster headache; Chronic cluster headache

Outcome Measures

Primary Outcomes (2)

• Percentage of Subjects Who Achieve Pain Relief

  Pain relief is defined by a decrease in pain from severe to mild or none without the use of acute rescue medication.

  15 minutes

• Percentage of Subjects Who Achieve Sustained Pain Relief

  Sustained pain relief requires a pain rating of mild or none at each timepoint from 15 minutes to 60 minutes without the use of acute rescue medication.

  15 minutes to 60 minutes

Secondary Outcomes (9)

• Percentage of Subjects That Achieve Pain Relief

  5 minutes

• Percentage of Subjects That Achieve Sustained Pain Relief

  5 minutes to 60 minutes

• Percentage of Subjects That Achieve Pain Freedom

  10 minutes

• Percentage of Subjects That Achieve Sustained Pain Freedom

  15 to 60 minutes

• Percentage of Subjects Able to Perform Their Usual Daily Activities as Assessed by the Subject

  within 20 minutes

Study Arms (3)

C213 1.9 mg

EXPERIMENTAL

C213, 1.9 mg administered as one 1.9 mg patch and one placebo patch

Drug: C213 Microneedle System

C213 3.8mg

EXPERIMENTAL

C213 3.8 mg administered as two 1.9 mg patches

Drug: C213 Microneedle System

Placebo

PLACEBO COMPARATOR

Placebo microneedle system administered as two placebo patches

Drug: Placebo

Interventions

C213 Microneedle System DRUG

The C213 System is a proprietary disposable patch and a reusable applicator. The zolmitriptan-coated titanium microneedle array (3 cm\^2 array) is attached to a 5 cm\^2 adhesive patch.

Also known as: Zolmitriptan Microneedle System

C213 1.9 mg; C213 3.8mg

Placebo DRUG

The C213 System is a proprietary disposable patch and a reusable applicator. The placebo patch is a single use, 3 cm\^2 Placebo (intracutaneous microneedle) system that contains no active ingredients.

Also known as: ZP Placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• Able to provide written informed consent
• Women or men 18 to 65 years of age
• Greater than 1-year history of episodic or chronic cluster headache with onset prior to 50 years of age. Diagnosis must comply with ICHD-3 (International Headache Society (IHS) diagnostic criteria). Diagnostic criteria must include a history of at least 5 attacks not attributed to any other disorder that include all of the following criteria:
• Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 45-180 minutes (average, when untreated)
• Either or both of the following:
• At least one of the following symptoms or signs, ipsilateral to the pain:
• Conjunctival injection and/or lacrimation
• Nasal congestion and/or rhinorrhea
• Eyelid edema
• Forehead and facial sweating
• Miosis and or/ptosis
• A sense of restlessness or agitation
• Attacks have a frequency between one every other day and eight per day for more than half of the time when the disorder is active.
• Not better accounted for by another International Classification of Headache Disorders (ICHD) diagnosis
• Cluster history during the 12-month period prior to the screening visit must include:

You may not qualify if:

• Contraindications to triptans
• Use of any prohibited concomitant medications within 30 days of screening
• History of hemiplegic migraine or migraine with brainstem aura
• Participation in another investigational trial within 30 days or 5 half-lives of investigational product (whichever is longer).
• Previous M207/C213 exposure in a clinical trial
• Subject has other significant pain problems that might confound the study assessments in the opinion of the investigator
• Diagnosis of any malignant disease (other than adequately treated or excised non-metastatic basal cell carcinoma or squamous cell carcinoma of the skin) within the 5 years prior to screening
• History of unstable psychiatric illness requiring medication or hospitalization in the 12 months prior to study initiation
• Subjects who have a known allergy or sensitivity to zolmitriptan or its derivatives or formulations
• Subjects who have a known allergy or sensitivity to adhesions
• Subjects who have skin lesions or tattoos covering the entire potential area(s) of C213 application
• Woman who are pregnant, breast-feeding or plan a pregnancy during this study
• Clinically significant liver disease \[Alanine Aminotransferase (ALT) \> 150 U/L; Aspartate Aminotransferase (AST) \> 130 U/L or bilirubin \> 2x ULN\]
• Clinically significant kidney disease (eGFR \< 60 ml/min / 1.73 m² or to creatinine \> 1.5 x ULN)
• Subject has clinically significant ECG findings, defined by:

Sponsors & Collaborators

• Zosano Pharma Corporation: lead

Study Sites (12)

Keck Medicine of USC

Los Angeles, California, 90033, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

California Medical Clinic for Headache

Santa Monica, California, 90404, United States

Location

KI Health Partners LLC DBA New England Institute for Clinical Research

Stamford, Connecticut, 06905, United States

Location

Atlanta Headache Specialists

Atlanta, Georgia, 30328, United States

Location

New England Regional Headache Center, Inc.

Worcester, Massachusetts, 01605, United States

Location

Nevada Headache Institute

Las Vegas, Nevada, 89113, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Dent Neuro Institute, Buffalo

Amherst, New York, 14226, United States

Location

Jefferson Headache Center

Philadelphia, Pennsylvania, 19107, United States

Location

University of Texas Southwestern Medical Center- Neurology Clinic

Dallas, Texas, 75390, United States

Location

Medstar Georgetown University Hospital at McLean

McLean, Virginia, 22101, United States

Location

MeSH Terms

Conditions

Cluster Headache

Condition Hierarchy (Ancestors)

Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Limitations and Caveats

The COVID-19 pandemic had significant impact: Enrollment was hampered; therefore, Zosano ended the trial with 42 subjects randomized and 23 subjects who treated a Cluster attack. The study was thus underpowered to detect a difference between C213 doses and placebo. The protocol was amended to allow for feasible assessments to be done virtually and permit in home monthly pregnancy testing. The monitoring plan and Zosano Pharma vendor management plan were updated to allow for remote monitoring.

Results Point of Contact

• Title: Don Kellerman, Sr. VP, Clinical Development and Medical Affairs
• Organization: Zosano Pharma Corporation

dkellerman@zosanopharma.com

+1 (510) 745-4004

Study Officials

• Don Kellerman, PharmD

  Zosano Pharma Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All subjects, care providers, investigator, and outcomes assessors are blinded to randomized treatment assignment. Study drugs are blinded and identical in appearance.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Qualified subjects are assigned to received a single administration of one of three blinded treatment assignments (one of two dose levels or placebo)

Study Record Dates

• First Submitted: August 19, 2019
• First Posted: August 22, 2019
• Study Start: October 3, 2019
• Primary Completion: April 14, 2021
• Study Completion: April 14, 2021
• Last Updated: June 14, 2022
• Results First Posted: May 2, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)