A Trial to Evaluate the Efficacy, Safety and Tolerability of Subcutaneous TRV250

NCT04201080 | Terminated Phase 1 DMC

• 1 other identifier: CP250-1002
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

A trial to assess the efficacy, safety, tolerability and effect of a drug (code name TRV250) given as an injection to subjects who have received an injection of a drug called glyceryl trinitrate (GTN) which is clinically known to induce an immediate headache of short duration (under 30 minutes), known as the "GTN immediate headache"

Conditions

Migraines

Outcome Measures

Primary Outcomes (1)

• The primary outcome of this study is the proportion of patients who experienced a headache from dosing up to 4 hours post-dose, that exceeds a verbal numerical rating scale (NRS) headache rating of ≥2 points.

  Verbal Numerical Rating (NRS) and Headache Characteristics (Pain Response, Pain Freedom, Nausea, Photophobia) Assessment: 0 minutes prestart of GTN infusion and every 15 minutes until 4 hours post-dose

  0-4 hours post-dose

Secondary Outcomes (18)

• The proportion of patients who experienced a headache occurring at various timepoints from dosing up to 8 hours post-dose, that exceeds a verbal NRS headache rating of ≥2 points

  0-8 hours post-dose

• The proportion of patients who experience a headache occurring at various timepoints from dosing up to 8 hours post-dose, that exceeds a verbal NRS headache rating of ≥3 points.

  0-8 hours post-dose

• The proportion of patients who experience a headache occurring at various timepoints from dosing up to 8 hours post-dose, that exceeds a verbal NRS headache rating of ≥4 points.

  0-8 hours post-dose

• Pain Response (PR) at 2-hour time point following injection of TRV250 or placebo

  every 2 hours for 24 hours

• PF at 2-hour time point following injection of TRV250 or placebo.

  every 2 hours for 24 hours

Other Outcomes (14)

• Migraine headache relapse defined as a verbal NRS headache score ≥4 points from the timepoint of Pain Response (PR) through 24 hours of follow-up.

  up to 24 hours of follow-up

• Sustained pain freedom between 2 and 24 hours (2-24H SPF).

  2-24 hours post dose

• Two-hour total migraine freedom (2H TMF; migraine freedom is defined as PF + no nausea + no vomiting + no photophobia + no phonophobia): TMF at 2-hour time point.

  2-hours

Study Arms (6)

Part A: TRV250 for SC injection

EXPERIMENTAL

2 SC injections of (10 mg/ml per injection)

Drug: Part A: TRV250-20mg/ml

Part A: Placebo for SC injection

PLACEBO COMPARATOR

2 SC injections (identical to the TRV250)

Drug: Placebo

Part B: TRV250 dose 1 for SC injection

EXPERIMENTAL

1 of 3 doses of TRV250 (using 2 identical syringes)

Drug: Part B: TRV250 Dose 1

Part B: TRV250 dose 2 for SC injection

EXPERIMENTAL

1 of 3 doses of TRV250 (using 2 identical syringes)

Drug: Part B: TRV250 Dose 2

Part B: TRV250 dose 3 for SC injection

EXPERIMENTAL

1 of 3 doses of TRV250 (using 2 identical syringes)

Drug: Part B: TRV250 Dose 3

Part B: Placebo for SC injection

PLACEBO COMPARATOR

Placebo (using syringes identical to the TRV250 arms)

Drug: Placebo

Interventions

Part A: TRV250-20mg/ml DRUG

TRV250 SC Injections

Also known as: Proof of concept

Part A: TRV250 for SC injection

Placebo DRUG

Placebo SC injections

Also known as: Proof of concept

Part A: Placebo for SC injection

Part B: TRV250 Dose 1 DRUG

Dose 1of3 TRV250

Also known as: Dose-ranging

Part B: TRV250 dose 1 for SC injection

Part B: TRV250 Dose 2 DRUG

Dose 2of3 TRV250 SC injections

Also known as: Dose-ranging

Part B: TRV250 dose 2 for SC injection

Part B: TRV250 Dose 3 DRUG

Dose 3of3 TRV250 SC injections

Also known as: Dose-ranging

Part B: TRV250 dose 3 for SC injection

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patient is male or female, aged between 18 and 55 years inclusive.
• Patient's Body Mass Index (BMI) is between 18 and 32 kg/m2 inclusive.
• Patient should have a clinical diagnosis of migraine without aura (IHS criteria 1.1) and experience between 1 migraine attack every other month to 8 migraine attacks per month. They should have had a positive outcome with Triptans, for their migraine attacks (Triptan Responders).

You may not qualify if:

• Patient has previous exposure to TRV250.
• Abnormal EEG at screening or risk factors of increased seizure potential, such as previous seizures, history of febrile seizures, cerebral tumor, stroke, cerebrovascular disease, or significant traumatic brain injury.
• Patient with a history of hypotension or hypertension, including where this is currently under control.
• Patient taking prophylactic migraine treatments such as beta blockers 28 days before GTN infusion on Day 1.
• Resting heart rate \<45 beats per minute on assessment of vital signs at screening or pre-GTN infusion on Day 1.
• QTcF \>450 msec at screening (mean of three ECGs) or pre-GTN infusion on Day 1.
• Patient with another headache disorder such as menstrual migraine, chronic migraine, cluster headache, tension headache or other chronic headache states.
• Patient who have a history, or family history of any vascular intracranial lesion such as subarachnoid aneurysm or similar and patients with a relevant neurological history.
• Patients who have any allergies/contraindications for Triptan administration.

Sponsors & Collaborators

• Trevena Inc.: lead

Study Sites (1)

MAC Clinical Research Manchester (Early Phase Unit), Neuroscience Centre of Excellence

Manchester, Greater Mancherster, M13 9NQ, United Kingdom

Location

MeSH Terms

Conditions

Migraine Disorders

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Dasyam, MBBS, Msc

  MAC Clinical Research Manchester (Early Phase Unit)

  PRINCIPAL INVESTIGATOR

• Nicklas, RN BSN CCRC

  Trevena Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Patients will be randomised to receive TRV250 20 mg or placebo in Part A and 1 of 3 doses of TRV250 or placebo in Part B. The study will be conducted in a double-blinded fashion (Investigator- and patient -blinded). Only unblinded personnel will have access to the randomisation list before official unblinding of treatment assignment. Interim analyses will be conducted at the end of Part A of the study prior to proceeding to Part B and the preliminary efficacy pharmacokinetic, safety and tolerability data will be evaluated unblinded at the end of Part A and shared with the Investigators in an unblinded manner, prior to starting Part B.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study consists of 2 parts: Part A is a proof of concept study; and Part B will be a dose ranging study

Study Record Dates

• First Submitted: December 5, 2019
• First Posted: December 17, 2019
• Study Start: November 11, 2019
• Primary Completion: February 17, 2020
• Study Completion: August 10, 2020
• Last Updated: September 22, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)