RP-008 in Combination With Daily Oral Varenicline for the Treatment of Trigeminal Neuralgia (RELIEF)

A Phase 1/2, Multicenter, Open-Label Study to Evaluate Safety, Tolerability, and PRELIminary EFficacy of Percutaneous Injection of RP-008 Followed by Daily Oral Varenicline in Patients With Trigeminal Neuralgia (The RELIEF Study)

The goal of this study is to evaluate if KRIYA-748 (RP-008) is safe, tolerable, and preliminary effective in treating trigeminal neuralgia (TN) when used in combination with varenicline tartrate. The study will also assess what doses of RP-008 are safe and tolerable for participants and how the severity of participants' TN pain and frequency of facial pain attacks are affected.

Study Overview

• Status: Recruiting
• Conditions: Trigeminal Neuralgia
• Intervention / Treatment: Genetic: RP-008; Drug: Varenicline tartrate

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: VP Medical Affairs; Phone Number: 984-884-5058; Email: clinicaltrials@kriyatx.com

Study Locations

• Canada
  • Sherbrooke, Canada
    • Recruiting
    • Kriya Clinical Study Site
    • Contact: Clinical Projects Coordinator; Phone Number: +1 819-346-1110; Email: chus@ssss.gouv.qc.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant is capable of providing signed informed consent.
• Participant must be between 18 to 80 years of age (inclusive), at the time of signing the informed consent.
• Confirmed diagnosis of classical TN according to the criteria of the International Classification of Headache Disorders-3rd edition (ICHD-3, 2018).
• The diagnosis of TN established at least 6 months prior to Screening.
• Participant has purely unilateral pain attacks limited primarily to the maxillary (V2) and/or mandibular (V3) division of the trigeminal nerve.
• Participant has failed at least 1 standard of care anti-epileptic agent (e.g., carbamazepine, oxcarbazepine, pregabalin, gabapentin, phenytoin, lamotrigine). Failure to a prior anti-epileptic medication is defined as insufficient pain relief despite use of a therapeutic dose for an adequate duration of time or being unsuitable due to contraindications or intolerance to side effects.

Exclusion Criteria:

• Participant has bilateral TN pain attacks.
• Participants with secondary TN, defined by ICHD-3 as TN caused by an underlying disease (e.g., tumor in the cerebellopontine angle, arteriovenous malformation, or multiple sclerosis).
• Participants with facial pain not meeting the ICHD-3 diagnostic criteria for TN, including: trigeminal autonomic cephalalgias, cluster headache, hemicrania continua, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA).
• Participants who had no change in pain after taking sodium channel blockers despite the use of a therapeutic dose for an adequate duration of time.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants receiving RP-008; Participants will receive a single dose of RP-008 on Day 1 at varying dose levels according to the dose escalation study design. In addition, varenicline tartrate and oral corticosteroid (equivalent to prednisone or prednisolone) will be administered during the pre- and post-treatment follow-up periods.	Genetic: RP-008; RP-008 will be administered as a single percutaneous injection to the trigeminal ganglion.; Other Names: KRIYA-748; Drug: Varenicline tartrate; Varenicline tartrate will be administered as a daily oral tablet.; Other Names: Champix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events, abnormal clinical laboratory values, abnormal physical examinations, abnormal vital signs, abnormal electrocardiograms (ECGs), and suicidal ideation	Safety of RP-008 with varenicline	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of responders, defined as participants with reduced TN pain score, attacks, and severity, to RP-008 with varenicline treatment	Efficacy of RP-008 with varenicline	3 and 12 months
Change in pain as assessed by the 11-point Numerical Pain Rating Scale (NRS), where 0 corresponds to "no pain" and 10 corresponds to "pain as bad as you can imagine"	Efficacy of RP-008 with varenicline	3 and 12 months
Change in pain as assessed by the Brief Pain Inventory (BPI) Pain Interference (PI) sub-scale, where 0 corresponds to pain having no interference with daily activities and 10 corresponds to pain interfering completely with daily activities	Efficacy of RP-008 with varenicline	3 and 12 months
Change from baseline in Pittsburgh Sleep Quality Index (PSQI), where scores range from 0-21 and higher score indicates worse sleep quality	Efficacy of RP-008 with varenicline	3 and 12 months
Change from baseline in Hospital Anxiety and Depression Scale (HADS), where sub-scale scores range from 0-21 and higher score indicates greater symptom severity	Efficacy of RP-008 with varenicline	3 and 12 months
Change from baseline in Work Productivity and Activity Impairment (WPAI): Neuropathic Pain v2.0, where scores are expressed as 0-100% and higher percentage indicates greater impairment	Efficacy of RP-008 with varenicline	3 and 12 months
Change from baseline in Penn Facial Pain Scale Revised (Penn-FPS-R), where scores range from 0-120 and higher score indicates greater pain-related disability	Efficacy of RP-008 with varenicline	3 and 12 months
Change from baseline in 5-level EuroQual-5D (EQ-5D-5L), where scores range from 0-100 and higher scores indicate better health status	Efficacy of RP-008 with varenicline	3 and 12 months
Change from baseline in Patient Global Assessment of TN (PGA-TN), where scores range from 1 to 5 and higher score indicates higher severity of symptoms and inability to carry out normal activities	Efficacy of RP-008 with varenicline	3 and 12 months
Change from baseline in Modified Barrow Neurological Institute Pain Intensity Score (BNI), where scores range from I to V and higher score indicates higher pain and need for medication	Efficacy of RP-008 with varenicline	3 and 12 months
Improvement in Patient Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) scale, where scores range from 1 to 7 and higher score indicates worsening of status	Efficacy of RP-008 with varenicline	3 and 12 months
AAV5 anti-capsid and anti-transgene antibody titer	Immune response to RP-008	12 months
Vector shedding profile of RP-008	Vector shedding in plasma, urine, tears, saliva, and mucus	12 months

Collaborators and Investigators

• Sponsor: Kriya Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: April 17, 2026
• First Submitted That Met QC Criteria: May 12, 2026
• First Posted (Actual): May 19, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Nervous System Diseases; Cranial Nerve Diseases; Trigeminal Nerve Diseases; Facial Neuralgia; Facial Nerve Diseases; Trigeminal Neuralgia; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzazepines; Quinoxalines; Varenicline
• Other Study ID Numbers: KT74863-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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